{ "data": [ { "slug": "semaglutide", "name": "Semaglutide", "aliases": [ "Ozempic", "Wegovy", "Rybelsus", "NN9535", "compounded semaglutide", "Wegovy pill", "Ozempic tablets" ], "class": "GLP-1 receptor agonist (31 amino acid analog of human GLP-1, acylated for once weekly dosing)", "one_liner": "FDA approved GLP-1 agonist with about 15% average weight loss in a 68 week RCT and proven cardiovascular benefit.", "summary": "Semaglutide is an FDA approved GLP-1 receptor agonist sold as Ozempic (type 2 diabetes, weekly injection or daily tablet), Wegovy (chronic weight management and cardiovascular risk reduction, weekly injection or daily tablet), and Rybelsus (daily tablet for type 2 diabetes). In the 68 week STEP 1 trial, adults with obesity lost 14.9% of body weight on Wegovy's 2.4 mg weekly dose versus 2.4% on placebo. Compounded versions were lawful only during the FDA declared shortage, which ended in February 2025.", "mechanism": "Semaglutide binds and activates the GLP-1 receptor. This increases glucose dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic and brainstem appetite centers to reduce hunger and food intake. A fatty acid side chain binds albumin, giving a half life of about one week.", "evidence_grade": "human_rct", "evidence_summary": "Multiple large randomized controlled trials. STEP 1 (n = 1,961) showed 14.9% mean weight loss at 68 weeks versus 2.4% with placebo. SUSTAIN-6 (n = 3,297) showed a 26% relative reduction in major adverse cardiovascular events in type 2 diabetes. SELECT (n = 17,604) showed a 20% relative reduction in major adverse cardiovascular events in adults with obesity and cardiovascular disease but without diabetes.", "human_evidence": "STEP 1: 1,961 adults with BMI 30 or higher (or 27 with a comorbidity), 2.4 mg weekly for 68 weeks, mean weight change of minus 14.9% versus minus 2.4% on placebo; 86.4% of the semaglutide group lost at least 5% of body weight. SUSTAIN-6: 3,297 adults with type 2 diabetes, hazard ratio 0.74 for major adverse cardiovascular events over about 2 years. SELECT: 17,604 adults with overweight or obesity and established cardiovascular disease, hazard ratio 0.80 for major adverse cardiovascular events over a mean 40 months.", "animal_evidence": "Preclinical rodent and primate studies established GLP-1 receptor mediated reductions in food intake and body weight and informed the human dose. Rodent studies also showed thyroid C cell tumors, which is the basis of the boxed warning; this finding has not been reproduced in humans.", "conditions": [ "obesity", "type-2-diabetes" ], "literature_dosing": "Weight management (STEP 1 and Wegovy label): start 0.25 mg subcutaneously once weekly, increase every 4 weeks through 0.5, 1.0, and 1.7 mg to a maintenance dose of 2.4 mg weekly. The Wegovy label also allows 1.7 mg as a maintenance dose and, for adults who tolerate 2.4 mg for at least 4 weeks, an increase to a 7.2 mg maximum for more weight reduction. Wegovy tablets: 1.5 mg daily for 30 days, then 4 mg and 9 mg, with 25 mg daily as maintenance. Type 2 diabetes (Ozempic label): 0.25 mg weekly for 4 weeks, then 0.5 mg, with optional increases to 1 mg and 2 mg weekly. Oral (Rybelsus label): 3 mg daily for 30 days then 7 mg, up to 14 mg.", "routes": [ "Subcutaneous injection once weekly (Ozempic, Wegovy)", "Oral tablet once daily (Wegovy tablets, Ozempic tablets, Rybelsus)" ], "side_effects": [ "Nausea (44% in STEP 1 versus 16% placebo)", "Diarrhea (32% versus 16%)", "Vomiting (24% versus 6%)", "Constipation (24% versus 11%)", "Gallbladder disease including gallstones", "Pancreatitis (rare)", "Hypoglycemia when combined with insulin or sulfonylureas", "Boxed warning for thyroid C cell tumors based on rodent data", "Reports of ileus and, rarely, non-arteritic anterior ischemic optic neuropathy under investigation" ], "interactions": [ "Insulin and sulfonylureas: increased risk of hypoglycemia, dose reduction of those agents is usually needed", "Oral medications with a narrow therapeutic window: delayed gastric emptying can change absorption (labels advise monitoring, for example with warfarin)", "Other GLP-1 or GIP/GLP-1 agonists: not studied in combination and not recommended" ], "contraindications": [ "Personal or family history of medullary thyroid carcinoma", "Multiple endocrine neoplasia syndrome type 2", "Prior serious hypersensitivity to semaglutide", "Pregnancy (discontinue at least 2 months before a planned pregnancy per label)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved products (Ozempic 2017, Rybelsus 2019, Wegovy 2021). FDA removed semaglutide from the drug shortage list on February 21, 2025; compounding by 503A pharmacies had to stop by April 22, 2025 and by 503B outsourcing facilities by May 22, 2025, except for a documented patient specific clinical need. FDA has warned about unapproved compounded and counterfeit GLP-1 products and salt forms (semaglutide sodium, semaglutide acetate) that are not the approved active ingredient. On April 30, 2026 FDA proposed not to include semaglutide on the 503B bulks list; that proposal was not final as of September 2026. Adding a vitamin such as B12 or niacinamide does not by itself make a compounded GLP-1 different from the approved drug. Under FDA's April 1, 2026 policy update, such a combination may be treated as essentially a copy when the strengths are within 10% of approved products and the route is the same, unless a prescriber documents a real difference for the individual patient. A September 2026 FDA warning letter applied this to semaglutide and tirzepatide vitamin combinations, said high production volume suggested the claimed differences were a pretext, and questioned significant-difference statements picked from preset menus on prescribing platforms.", "typical_cost": "Manufacturer list price is 1,349.02 USD per month for Wegovy and 1,027.51 USD for Ozempic (checked 2026-09-22), falling to 675 USD for both on January 1, 2027. Manufacturer self-pay prices run 149 to 499 USD per month by product and dose, with the Wegovy pen at 349 USD. With commercial insurance the manufacturer savings offer can bring a covered prescription to 25 USD per month, and eligible Medicare Part D enrollees pay 50 USD per month for Wegovy under the Medicare GLP-1 Bridge (July 2026 to December 2027). A 2024 study found compounded semaglutide at a median 231 USD for the first month during the shortage; compounding is now limited to patient specific needs.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail pharmacy as Ozempic, Wegovy, or Rybelsus.", "FDA's Drug Shortages database lists Rybelsus 3 mg, 7 mg, and 14 mg tablets as To Be Discontinued, posted June 4, 2026; ask the prescriber or pharmacy which oral semaglutide product replaces them.", "Manufacturer direct-to-consumer cash pay program for Wegovy.", "Compounded semaglutide is no longer lawful for routine dispensing after the 2025 shortage resolution; ask any provider offering it what the documented clinical need is." ], "faqs": [ { "q": "Is semaglutide (Wegovy, Ozempic) FDA approved and legal?", "a": "Yes. Semaglutide is FDA approved as Ozempic (type 2 diabetes, 2017), Rybelsus (oral, type 2 diabetes, 2019), and Wegovy (chronic weight management, 2021). Wegovy's label has since added cardiovascular risk reduction, noncirrhotic MASH with liver fibrosis, and a once daily tablet for weight management, and Ozempic's label covers kidney outcomes in type 2 diabetes with chronic kidney disease. It is available only by prescription. Compounded copies were permitted only while FDA listed the drug as in shortage; that listing ended February 21, 2025.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-glp1-compounding" ] }, { "q": "Is Ozempic a peptide?", "a": "Yes. Semaglutide, the active ingredient in Ozempic, Wegovy, and Rybelsus, is a modified version of GLP-1, a 31 amino acid gut hormone. The labels describe a peptide backbone made by yeast fermentation, changed at one position to resist breakdown and linked to a fatty acid that binds albumin, which stretches its half life to about a week. So it is a peptide drug, but unlike peptides sold online as research chemicals it is FDA approved and made under pharmaceutical quality rules.", "source_ids": [ "fda-ozempic-label", "fda-wegovy-label" ] }, { "q": "How much weight do people lose on Wegovy (semaglutide)?", "a": "In the STEP 1 randomized trial of 1,961 adults with obesity, the semaglutide 2.4 mg group lost a mean 14.9% of body weight over 68 weeks versus 2.4% on placebo. About 86% of participants lost at least 5% and about a third lost 20% or more. Weight regain is expected after stopping: in the STEP 1 extension, participants regained about two thirds of lost weight within a year off treatment.", "source_ids": [ "step-1" ] }, { "q": "What are the side effects of Wegovy and Ozempic?", "a": "Both brands are semaglutide, so the side effects are the same kind, with gastrointestinal effects most common. In STEP 1 (Wegovy 2.4 mg), nausea affected 44% of the semaglutide group versus 16% on placebo, diarrhea 32% versus 16%, vomiting 24% versus 6%, and constipation 24% versus 11%. Most were mild to moderate and eased with time. Less common but serious risks include gallbladder disease, pancreatitis, and hypoglycemia when combined with insulin or sulfonylureas. Both labels carry a boxed warning for thyroid C cell tumors seen in rodents.", "source_ids": [ "step-1", "fda-wegovy-label", "fda-ozempic-label" ] }, { "q": "What is the Wegovy and Ozempic dose schedule on the FDA label?", "a": "Wegovy injection starts at 0.25 mg once weekly for 4 weeks, then rises every 4 weeks to 0.5 mg, 1 mg, and 1.7 mg. The usual maintenance dose is 2.4 mg weekly, and adults who tolerate 2.4 mg for at least 4 weeks may go up to a 7.2 mg maximum. Wegovy tablets start at 1.5 mg daily for 30 days, then 4 mg and 9 mg, with 25 mg daily as maintenance. Ozempic for type 2 diabetes starts at 0.25 mg weekly, then 0.5 mg, with optional steps to 1 mg and 2 mg. Injections go under the skin of the abdomen, thigh, or upper arm. The prescriber sets the dose.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label" ] }, { "q": "How much do Wegovy and Ozempic cost?", "a": "Wegovy's list price is 1,349.02 USD per month and Ozempic's 1,027.51 USD, but few people pay list, and the manufacturer has announced a 675 USD list price for both from January 1, 2027. Manufacturer self-pay prices, checked 2026-09-22, are 149 to 299 USD per month for the tablets and 349 USD for the Wegovy pen (399 USD for the 7.2 mg dose, 199 USD for new patients' first two starting-dose fills). Commercial insurance with the manufacturer savings offer can bring a covered prescription to 25 USD, and eligible Medicare Part D enrollees pay 50 USD per month for Wegovy under the Medicare GLP-1 Bridge through December 31, 2027.", "source_ids": [ "price-list-weight", "price-list-diabetes", "price-list-cut-2027", "price-self-pay", "price-savings-offer", "medicare-glp1-bridge" ] }, { "q": "Does semaglutide protect the heart?", "a": "Yes, in two large trials. SUSTAIN-6 (3,297 people with type 2 diabetes) found a 26% relative reduction in major adverse cardiovascular events. SELECT (17,604 people with obesity and cardiovascular disease but no diabetes) found a 20% relative reduction over a mean 40 months, which led to the 2024 cardiovascular risk reduction indication for Wegovy.", "source_ids": [ "sustain-6", "select", "fda-wegovy-label" ] }, { "q": "Wegovy vs Zepbound: which works better?", "a": "For weight loss, Zepbound's ingredient tirzepatide won the only direct obesity trial: in SURMOUNT-5, adults lost 20.2% of body weight on tirzepatide versus 13.7% on semaglutide at 72 weeks. In type 2 diabetes, SURPASS-2 also favored tirzepatide over semaglutide 1 mg on HbA1c and weight. Semaglutide has what tirzepatide lacks in obesity: a completed cardiovascular outcomes trial (SELECT) and a tablet form. Both carry the same thyroid boxed warning, and cost and coverage often decide.", "source_ids": [ "surmount-5", "surpass-2", "select" ] } ], "studies": [ { "pmid": "33567185", "title": "Once-weekly semaglutide in adults with overweight or obesity (STEP 1)", "year": 2021, "design": "Randomized, double blind, placebo controlled trial, 68 weeks", "n": 1961, "population": "Adults with BMI 30 or higher, or 27 or higher with at least one weight related comorbidity, without diabetes", "outcome": "Mean weight change minus 14.9% with semaglutide 2.4 mg versus minus 2.4% with placebo; 86.4% versus 31.5% achieved at least 5% weight loss", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33567185/" }, { "pmid": "27633186", "title": "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6)", "year": 2016, "design": "Randomized, double blind, placebo controlled cardiovascular outcomes trial, median 2.1 years", "n": 3297, "population": "Adults with type 2 diabetes at high cardiovascular risk", "outcome": "Major adverse cardiovascular events hazard ratio 0.74 (95% CI 0.58 to 0.95) versus placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27633186/" }, { "pmid": "37952131", "title": "Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT)", "year": 2023, "design": "Randomized, double blind, placebo controlled cardiovascular outcomes trial, mean follow up 39.8 months", "n": 17604, "population": "Adults 45 and older with BMI 27 or higher and established cardiovascular disease, without diabetes", "outcome": "Major adverse cardiovascular events hazard ratio 0.80 (95% CI 0.72 to 0.90) versus placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37952131/" }, { "pmid": "34170647", "title": "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2)", "year": 2021, "design": "Randomized, open label, active comparator trial, 40 weeks", "n": 1879, "population": "Adults with type 2 diabetes on metformin", "outcome": "Tirzepatide 5, 10, and 15 mg lowered HbA1c and body weight more than semaglutide 1 mg (weight minus 7.6 to minus 11.2 kg versus minus 5.7 kg)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/" } ], "sources": [ { "id": "step-1", "type": "pubmed", "title": "Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021 (STEP 1)", "url": "https://pubmed.ncbi.nlm.nih.gov/33567185/", "pmid": "33567185", "year": 2021 }, { "id": "sustain-6", "type": "pubmed", "title": "Marso SP et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016 (SUSTAIN-6)", "url": "https://pubmed.ncbi.nlm.nih.gov/27633186/", "pmid": "27633186", "year": 2016 }, { "id": "select", "type": "pubmed", "title": "Lincoff AM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023 (SELECT)", "url": "https://pubmed.ncbi.nlm.nih.gov/37952131/", "pmid": "37952131", "year": 2023 }, { "id": "surpass-2", "type": "pubmed", "title": "Frias JP et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021 (SURPASS-2)", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/", "pmid": "34170647", "year": 2021 }, { "id": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection and tablets, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy", "year": 2025 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss, including shortage resolution and compounding deadlines", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-list-weight", "type": "other", "title": "Manufacturer list price (wholesale acquisition cost) page for semaglutide for weight management, accessed 2026-09-22", "url": "https://www.novopricing.com/wegovy.html", "year": 2026 }, { "id": "price-list-diabetes", "type": "other", "title": "Manufacturer list price (wholesale acquisition cost) page for semaglutide for type 2 diabetes, accessed 2026-09-22", "url": "https://www.novopricing.com/ozempic.html", "year": 2026 }, { "id": "price-list-cut-2027", "type": "other", "title": "Manufacturer press release: semaglutide list price lowered to 675 USD per month effective January 1, 2027, self-pay prices unchanged (February 24, 2026)", "url": "https://www.prnewswire.com/news-releases/novo-nordisk-announces-significant-reduction-in-us-list-price-for-wegovy-ozempic-and-rybelsus-semaglutide-medicines-building-on-continued-efforts-to-expand-access-302695705.html", "year": 2026 }, { "id": "price-self-pay", "type": "other", "title": "Manufacturer direct-to-patient pharmacy page with semaglutide self-pay and commercial savings prices, accessed 2026-09-22", "url": "https://www.novocare.com/pharmacy.html", "year": 2026 }, { "id": "price-savings-offer", "type": "other", "title": "Manufacturer savings offer terms for semaglutide for weight management (commercial insurance and self-pay), accessed 2026-09-22", "url": "https://www.novocare.com/patient/medicines/wegovy/savings-offer.html", "year": 2026 }, { "id": "medicare-glp1-bridge", "type": "other", "title": "Medicare.gov: weight loss drugs, Medicare GLP-1 Bridge coverage, eligibility, and 50 USD copay, accessed 2026-09-22", "url": "https://www.medicare.gov/coverage/weight-loss-drugs", "year": 2026 }, { "id": "compounded-glp1-price-study", "type": "pubmed", "title": "Online advertising of compounded glucagon-like peptide-1 receptor agonists (JAMA Health Forum, 2025): cross-sectional study of 79 websites with first-month prices", "url": "https://pubmed.ncbi.nlm.nih.gov/39820389/", "pmid": "39820389", "year": 2025 }, { "id": "fda-ozempic-label", "type": "fda", "title": "FDA prescribing information for Ozempic (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=ozempic" }, { "id": "fda-rybelsus-label", "type": "fda", "title": "FDA prescribing information for Rybelsus and Ozempic (semaglutide) tablets, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=rybelsus" }, { "id": "surmount-5", "type": "pubmed", "title": "Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med 2025 (SURMOUNT-5)", "url": "https://pubmed.ncbi.nlm.nih.gov/40353578/", "pmid": "40353578", "year": 2025 }, { "id": "fda-glp1-shortage-updates", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (GLP-1 shortage status updates, including liraglutide, and the April 1, 2026 policy update on essentially copies)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "year": 2026 }, { "id": "fr-2026-08552", "type": "federal_register", "title": "Federal Register 2026-08552: List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B (proposed May 1, 2026; comments extended to July 30, 2026)", "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "year": 2026 }, { "id": "fda-warning-letter-2026-09-18", "type": "fda", "title": "FDA warning letter to a compounding pharmacy on semaglutide and tirzepatide vitamin combinations (September 18, 2026)", "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/empower-clinic-services-llc-dba-empower-pharmacy-738238-09182026", "year": 2026 }, { "id": "fda-drug-shortages-semaglutide", "type": "fda", "title": "FDA Drug Shortages: semaglutide tablet (Rybelsus 3, 7, and 14 mg listed To Be Discontinued, posted June 4, 2026; checked September 27, 2026)", "url": "https://dps.fda.gov/drugshortages", "year": 2026 } ], "related": [ "tirzepatide", "liraglutide", "retatrutide", "cagrilintide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Semaglutide (Wegovy, Ozempic): evidence and access", "description": "Wegovy, Ozempic, and Rybelsus are all semaglutide. Trial weight loss, side effects, the FDA label dose schedule, heart data, cost, and legal status, sourced.", "h1": "Semaglutide (Wegovy, Ozempic, Rybelsus)", "headings": { "safety": "Wegovy and Ozempic side effects in trials", "dosing": "Semaglutide dose schedule on the FDA label" } } }, { "slug": "tirzepatide", "name": "Tirzepatide", "aliases": [ "Mounjaro", "Zepbound", "LY3298176", "compounded tirzepatide", "Zepbound KwikPen", "Mounjaro KwikPen" ], "class": "Dual GIP and GLP-1 receptor agonist (39 amino acid peptide, acylated for once weekly dosing)", "one_liner": "FDA approved weekly GIP and GLP-1 drug with 20.9% average weight loss at 15 mg in a 72 week randomized trial; beat semaglutide head to head.", "summary": "Tirzepatide is an FDA approved once weekly injectable that activates the receptors for two gut hormones, GIP and GLP-1, which boost insulin and curb appetite. It is one molecule sold under two brand names: Mounjaro for type 2 diabetes (2022) and, since August 2026, lowering cardiovascular risk (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes at high cardiovascular risk, and Zepbound for chronic weight management (2023) and obstructive sleep apnea (breathing that repeatedly stops during sleep) in obesity (2024). In the 72 week SURMOUNT-1 trial, adults with obesity lost a mean 20.9% of body weight on 15 mg versus 3.1% on placebo, and in the head to head SURMOUNT-5 trial it beat semaglutide, 20.2% versus 13.7%.", "mechanism": "Tirzepatide is a single peptide that activates the GIP receptor and the GLP-1 receptor. GLP-1 receptor activation increases glucose dependent insulin release, suppresses glucagon, slows gastric emptying, and reduces appetite. GIP receptor activation appears to add further appetite and insulin effects and may improve tolerability. The C20 fatty diacid moiety binds albumin for a half life of about 5 days.", "evidence_grade": "human_rct", "evidence_summary": "Large randomized controlled trials in both obesity and type 2 diabetes. SURMOUNT-1 (n = 2,539) showed 15.0%, 19.5%, and 20.9% mean weight loss at 5, 10, and 15 mg over 72 weeks versus 3.1% with placebo. SURPASS-2 (n = 1,879) showed superior HbA1c and weight reduction versus semaglutide 1 mg. A dedicated cardiovascular outcomes trial (SURPASS-CVOT) reported non-inferiority to dulaglutide in 2025. FDA added a cardiovascular risk reduction indication to Mounjaro in August 2026 on the basis of this trial (hazard ratio 0.92 versus dulaglutide, non-inferior but not superior).", "human_evidence": "SURMOUNT-1: 2,539 adults with obesity or overweight without diabetes, 72 weeks; mean weight change minus 15.0% (5 mg), minus 19.5% (10 mg), minus 20.9% (15 mg) versus minus 3.1% (placebo); 91% of the 15 mg group lost at least 5%. SURPASS-2: 1,879 adults with type 2 diabetes; HbA1c reductions of 2.01 to 2.30 percentage points versus 1.86 with semaglutide 1 mg, and weight change of minus 7.6 to minus 11.2 kg versus minus 5.7 kg. Additional SURMOUNT and SURPASS trials cover diabetes with obesity, obstructive sleep apnea, and maintenance after weight loss.", "animal_evidence": "Preclinical rodent studies established the dual agonist pharmacology and appetite effects. Rodent studies also showed thyroid C cell tumors, the basis for the boxed warning shared with other GLP-1 agonists; this has not been reproduced in humans.", "conditions": [ "obesity", "type-2-diabetes", "sleep" ], "literature_dosing": "SURMOUNT-1 and the FDA labels (Zepbound and Mounjaro): start 2.5 mg subcutaneously once weekly for 4 weeks, then increase in 2.5 mg steps every 4 weeks as tolerated to a maintenance dose of 5, 10, or 15 mg weekly. The 2.5 mg dose is for initiation only and is not a maintenance dose. Each step comes after at least 4 weeks on the current dose. Zepbound maintenance for obstructive sleep apnea is 10 or 15 mg weekly. The maximum is 15 mg weekly in adults and 10 mg weekly in children 10 and older on Mounjaro. Both brands come as 2.5, 5, 7.5, 10, 12.5, and 15 mg single-dose pens or vials, plus 4 dose KwikPens and multi-dose vials.", "routes": [ "Subcutaneous injection once weekly (pen or single dose vial)" ], "side_effects": [ "Nausea (31% at 15 mg in SURMOUNT-1 versus 10% placebo)", "Diarrhea (23% at 15 mg versus 7%)", "Vomiting (12% at 15 mg versus 2%)", "Constipation (12% at 15 mg versus 6%)", "Injection site reactions", "Gallbladder disease", "Pancreatitis (rare)", "Hypoglycemia when combined with insulin or sulfonylureas", "Boxed warning for thyroid C cell tumors based on rodent data" ], "interactions": [ "Insulin and sulfonylureas: increased risk of hypoglycemia, dose reduction usually needed", "Oral hormonal contraceptives: label advises a barrier method for 4 weeks after starting and after each dose increase because delayed gastric emptying can reduce absorption", "Oral drugs with a narrow therapeutic window: absorption may change with delayed gastric emptying", "Other GLP-1 or GIP/GLP-1 agonists: not studied in combination and not recommended" ], "contraindications": [ "Personal or family history of medullary thyroid carcinoma", "Multiple endocrine neoplasia syndrome type 2", "Prior serious hypersensitivity to tirzepatide", "Pregnancy (limited data; label advises discontinuation)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved products (Mounjaro May 2022, Zepbound November 2023). FDA declared the tirzepatide shortage resolved on December 19, 2024; compounding by 503A pharmacies had to stop by February 18, 2025 and by 503B outsourcing facilities by March 19, 2025, except for a documented patient specific clinical need. FDA has warned about unapproved compounded and counterfeit tirzepatide products. On April 30, 2026 FDA proposed not to include tirzepatide on the 503B bulks list; that proposal was not final as of September 2026. Adding a vitamin such as B12 or niacinamide does not by itself make a compounded GLP-1 different from the approved drug. Under FDA's April 1, 2026 policy update, such a combination may be treated as essentially a copy when the strengths are within 10% of approved products and the route is the same, unless a prescriber documents a real difference for the individual patient. A September 2026 FDA warning letter applied this to semaglutide and tirzepatide vitamin combinations, said high production volume suggested the claimed differences were a pretext, and questioned significant-difference statements picked from preset menus on prescribing platforms.", "typical_cost": "Manufacturer list price is up to 1,086.37 USD per fill for Zepbound and 1,112.16 USD for Mounjaro (checked 2026-09-22). Manufacturer self-pay Zepbound vials and KwikPen cost 299 USD per month at 2.5 mg, 399 at 5 mg, 499 at 7.5 mg, and 699 at 10 mg and above, with a 449 USD on-time refill offer for the 7.5 mg and higher KwikPen through 2026. With commercial insurance a savings card can bring a covered prescription to 25 USD, and eligible Medicare Part D enrollees pay 50 USD per month for the Zepbound KwikPen under the Medicare GLP-1 Bridge (July 2026 to December 2027). A study published in 2025 found compounded tirzepatide advertised at a median 330 USD for the first month during the shortage; compounding is now limited to patient specific needs.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail pharmacy as Mounjaro or Zepbound.", "Manufacturer direct-to-consumer cash pay program for Zepbound single dose vials.", "Compounded tirzepatide is no longer lawful for routine dispensing after the 2025 shortage resolution." ], "faqs": [ { "q": "Is tirzepatide (Zepbound, Mounjaro) FDA approved and legal?", "a": "Yes. Tirzepatide is FDA approved as Mounjaro for type 2 diabetes (May 2022) and as Zepbound for chronic weight management (November 2023) and moderate to severe obstructive sleep apnea (breathing that repeatedly stops during sleep) in adults with obesity (December 2024). The current Mounjaro label also covers children 10 and older with type 2 diabetes and lowering the risk of major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes at high risk. It is prescription only. Compounded (pharmacy-made) copies were broadly permitted only while FDA listed the drug as in shortage; that ended December 19, 2024, with a wind down through March 2025, and compounding is now limited to a documented patient specific clinical need.", "source_ids": [ "fda-zepbound-label", "fda-mounjaro-label", "fda-glp1-compounding" ] }, { "q": "Is Zepbound the same as Mounjaro?", "a": "Same drug, different labels. Both contain tirzepatide in the same six strengths from 2.5 mg to 15 mg, start at the same 2.5 mg weekly dose, and carry the same boxed warning. The difference is the approved use: Mounjaro is labeled for type 2 diabetes and for lowering cardiovascular risk in type 2 diabetes, while Zepbound is labeled for chronic weight management and for obstructive sleep apnea in adults with obesity. That label difference is what drives insurance coverage and price. The labels say not to combine tirzepatide products with each other or with another GLP-1 drug.", "source_ids": [ "fda-zepbound-label", "fda-mounjaro-label" ] }, { "q": "How much weight do people lose on tirzepatide?", "a": "In SURMOUNT-1, a 72 week randomized trial of 2,539 adults with obesity, mean weight loss was 15.0% at 5 mg, 19.5% at 10 mg, and 20.9% at 15 mg, versus 3.1% on placebo. At 15 mg, 91% lost at least 5% and 57% lost at least 20%. In SURMOUNT-5, the direct comparison with semaglutide in 751 adults with obesity, weight loss at 72 weeks was 20.2% with tirzepatide versus 13.7% with semaglutide. Weight regain occurs after stopping, so it is treated as a long term therapy.", "source_ids": [ "surmount-1", "surmount-5" ] }, { "q": "What are the side effects of Zepbound and Mounjaro?", "a": "Because both brands are the same molecule, they share one side effect profile, mostly gastrointestinal and dose related. In SURMOUNT-1 at 15 mg, nausea affected about 31% of participants versus 10% on placebo, diarrhea 23% versus 7%, vomiting 12% versus 2%, and constipation 12% versus 6%. Most events were mild to moderate and occurred during dose escalation. Serious but uncommon risks include gallbladder disease, pancreatitis, and hypoglycemia when combined with insulin or sulfonylureas. Both labels carry a boxed warning for thyroid C cell tumors seen in rodents.", "source_ids": [ "surmount-1", "fda-zepbound-label", "fda-mounjaro-label" ] }, { "q": "What is the tirzepatide dose schedule on the FDA label?", "a": "Both labels start at 2.5 mg injected under the skin once weekly for 4 weeks; 2.5 mg is a starting dose only. The dose then goes to 5 mg and can rise in 2.5 mg steps (7.5, 10, 12.5, and 15 mg), each after at least 4 weeks on the current dose. Zepbound's maintenance doses are 5, 10, or 15 mg weekly for weight reduction and 10 or 15 mg for sleep apnea. The maximum is 15 mg weekly in adults, and 10 mg for children on Mounjaro. A missed dose can be taken within 4 days. The prescriber sets the dose.", "source_ids": [ "fda-zepbound-label", "fda-mounjaro-label" ] }, { "q": "Where is Zepbound injected?", "a": "Under the skin of the abdomen or thigh, or the back of the upper arm when another person gives the injection, according to both the Zepbound and Mounjaro labels. The labels say to rotate the injection site with each weekly dose, and the dose can be taken at any time of day, with or without meals. Tirzepatide comes as a single-dose pen, single-dose vial, multi-dose vial, or KwikPen, and the labels ask prescribers to train patients on the specific presentation they receive.", "source_ids": [ "fda-zepbound-label", "fda-mounjaro-label" ] }, { "q": "How much does Zepbound cost?", "a": "Zepbound's list price is up to 1,086.37 USD per fill and Mounjaro's 1,112.16 USD, but few people pay list. Manufacturer self-pay prices, checked 2026-09-22, are 299 to 699 USD per month for Zepbound vials or the KwikPen depending on dose, and a commercial insurance savings card can bring a covered prescription to 25 USD. Medicare Part D covers Mounjaro for type 2 diabetes, and since July 1, 2026 eligible Part D enrollees can get the Zepbound KwikPen for weight management at a 50 USD monthly copay under the Medicare GLP-1 Bridge, which runs through December 31, 2027.", "source_ids": [ "price-info-weight", "price-info-diabetes", "price-savings-weight", "medicare-glp1-bridge" ] }, { "q": "Does Zepbound help sleep apnea?", "a": "Yes. FDA approved Zepbound in December 2024 for moderate to severe obstructive sleep apnea in adults with obesity, the first medicine approved for it. In the two 52 week SURMOUNT-OSA trials, the apnea hypopnea index fell by 25.3 and 29.3 events per hour with tirzepatide versus 5.3 and 5.5 with placebo, from starting averages of about 50 events per hour. The label's maintenance dose for sleep apnea is 10 or 15 mg weekly.", "source_ids": [ "fda-zepbound-label", "surmount-osa" ] } ], "studies": [ { "pmid": "35658024", "title": "Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)", "year": 2022, "design": "Randomized, double blind, placebo controlled trial, 72 weeks", "n": 2539, "population": "Adults with BMI 30 or higher, or 27 or higher with at least one weight related complication, without diabetes", "outcome": "Mean weight change minus 15.0% (5 mg), minus 19.5% (10 mg), minus 20.9% (15 mg) versus minus 3.1% (placebo)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/" }, { "pmid": "34170647", "title": "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2)", "year": 2021, "design": "Randomized, open label, active comparator trial, 40 weeks", "n": 1879, "population": "Adults with type 2 diabetes inadequately controlled on metformin", "outcome": "HbA1c change minus 2.01 to minus 2.30 percentage points versus minus 1.86 with semaglutide 1 mg; weight change minus 7.6 to minus 11.2 kg versus minus 5.7 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/" }, { "pmid": "41406444", "title": "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT)", "year": 2025, "design": "Randomized, double blind, active comparator cardiovascular outcomes trial", "n": 13165, "population": "Adults with type 2 diabetes and atherosclerotic cardiovascular disease", "outcome": "MACE-3 in 12.2% versus 13.1% with dulaglutide; hazard ratio 0.92 (95.3% CI 0.83 to 1.01); non-inferior, superiority not shown", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/41406444/" } ], "sources": [ { "id": "surmount-1", "type": "pubmed", "title": "Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022 (SURMOUNT-1)", "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/", "pmid": "35658024", "year": 2022 }, { "id": "surpass-2", "type": "pubmed", "title": "Frias JP et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021 (SURPASS-2)", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/", "pmid": "34170647", "year": 2021 }, { "id": "fda-zepbound-label", "type": "fda", "title": "FDA prescribing information for Zepbound (tirzepatide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=zepbound", "year": 2025 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss, including shortage resolution and compounding deadlines", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-info-weight", "type": "other", "title": "Manufacturer pricing information page for tirzepatide for weight management: list price, self-pay prices by dose, and commercial savings card, accessed 2026-09-22", "url": "https://pricinginfo.lilly.com/zepbound", "year": 2026 }, { "id": "price-info-diabetes", "type": "other", "title": "Manufacturer pricing information page for tirzepatide for type 2 diabetes: list price and savings card eligibility, accessed 2026-09-22", "url": "https://pricinginfo.lilly.com/mounjaro", "year": 2026 }, { "id": "price-savings-weight", "type": "other", "title": "Manufacturer savings and self-pay terms for tirzepatide for weight management, including the KwikPen refill offer, accessed 2026-09-22", "url": "https://zepbound.lilly.com/savings", "year": 2026 }, { "id": "medicare-glp1-bridge", "type": "other", "title": "Medicare.gov: weight loss drugs, Medicare GLP-1 Bridge coverage, eligibility, and 50 USD copay, accessed 2026-09-22", "url": "https://www.medicare.gov/coverage/weight-loss-drugs", "year": 2026 }, { "id": "compounded-glp1-price-study", "type": "pubmed", "title": "Online advertising of compounded glucagon-like peptide-1 receptor agonists (JAMA Health Forum, 2025): cross-sectional study of 79 websites with first-month prices", "url": "https://pubmed.ncbi.nlm.nih.gov/39820389/", "pmid": "39820389", "year": 2025 }, { "id": "fda-mounjaro-label", "type": "fda", "title": "FDA prescribing information for Mounjaro (tirzepatide) injection, via DailyMed (label revised 2026)", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=mounjaro" }, { "id": "surmount-5", "type": "pubmed", "title": "Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med 2025 (SURMOUNT-5)", "url": "https://pubmed.ncbi.nlm.nih.gov/40353578/", "pmid": "40353578", "year": 2025 }, { "id": "surmount-osa", "type": "pubmed", "title": "Malhotra A et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024 (SURMOUNT-OSA)", "url": "https://pubmed.ncbi.nlm.nih.gov/38912654/", "pmid": "38912654", "year": 2024 }, { "id": "fda-glp1-shortage-updates", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (GLP-1 shortage status updates, including liraglutide, and the April 1, 2026 policy update on essentially copies)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "year": 2026 }, { "id": "fr-2026-08552", "type": "federal_register", "title": "Federal Register 2026-08552: List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B (proposed May 1, 2026; comments extended to July 30, 2026)", "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "year": 2026 }, { "id": "fda-warning-letter-2026-09-18", "type": "fda", "title": "FDA warning letter to a compounding pharmacy on semaglutide and tirzepatide vitamin combinations (September 18, 2026)", "url": "https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/empower-clinic-services-llc-dba-empower-pharmacy-738238-09182026", "year": 2026 }, { "id": "surpass-cvot", "type": "pubmed", "title": "Nicholls SJ et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med 2025 (SURPASS-CVOT)", "url": "https://pubmed.ncbi.nlm.nih.gov/41406444/", "pmid": "41406444", "year": 2025 }, { "id": "lilly-mounjaro-cv-approval", "type": "other", "title": "Manufacturer press release: FDA approves Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes (August 28, 2026)", "url": "https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes-302862415.html", "year": 2026 } ], "related": [ "semaglutide", "retatrutide", "liraglutide", "cagrilintide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Tirzepatide (Zepbound, Mounjaro): evidence and access", "description": "Zepbound and Mounjaro are both tirzepatide. Trial weight loss, side effects, the FDA label dose schedule, injection sites, cost, and legal status, sourced.", "h1": "Tirzepatide (Zepbound, Mounjaro)", "headings": { "safety": "Zepbound and Mounjaro side effects in trials", "dosing": "Tirzepatide dose schedule on the FDA label" } } }, { "slug": "liraglutide", "name": "Liraglutide", "aliases": [ "Victoza", "Saxenda", "NN2211", "generic liraglutide", "Xultophy (with insulin degludec)", "Saxenda pen" ], "class": "GLP-1 receptor agonist (acylated analog of human GLP-1, 97% sequence homology, once daily dosing)", "one_liner": "First daily GLP-1 drug: FDA approved since 2010, about 8% weight loss at 3 mg over 56 weeks, proven heart benefit, now available as a generic.", "summary": "Liraglutide is an FDA approved once daily GLP-1 receptor agonist (a drug that mimics GLP-1, a gut hormone that boosts insulin and curbs appetite) sold as Victoza (type 2 diabetes, 2010) and Saxenda (chronic weight management, 2014), with generic versions approved from December 2024. In the 56 week SCALE trial, adults with obesity lost a mean 8.4 kg (about 8.0% of body weight) on 3.0 mg versus 2.8 kg on placebo, and in the LEADER trial it cut major adverse cardiovascular events (heart attack, stroke, or cardiovascular death) by 13% in people with type 2 diabetes. It is prescription only, and FDA's Drug Shortages database still lists liraglutide injection as in shortage as of September 2026, with Victoza and Saxenda at limited availability.", "mechanism": "Liraglutide binds and activates the GLP-1 receptor, increasing glucose dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite through hypothalamic and brainstem pathways. A C16 fatty acid side chain binds albumin, extending the half life to about 13 hours, which is why it is injected once daily rather than once weekly like semaglutide.", "evidence_grade": "human_rct", "evidence_summary": "Large randomized controlled trials in both obesity and type 2 diabetes. SCALE Obesity and Prediabetes (n = 3,731) showed 8.4 kg versus 2.8 kg weight loss at 56 weeks. SCALE Diabetes (n = 846) showed 6.0% versus 2.0% weight loss in people with type 2 diabetes. LEADER (n = 9,340) showed a hazard ratio of 0.87 for major adverse cardiovascular events over a median 3.8 years. In head to head trials it produces less weight loss than semaglutide 2.4 mg and cagrilintide 4.5 mg.", "human_evidence": "SCALE Obesity and Prediabetes: 3,731 adults without diabetes with BMI 30 or higher (or 27 with dyslipidemia or hypertension), 3.0 mg daily for 56 weeks; mean weight loss 8.4 kg versus 2.8 kg on placebo; 63.2% versus 27.1% lost at least 5%, and 33.1% versus 10.6% lost more than 10%. SCALE Diabetes: 846 adults with type 2 diabetes, 56 weeks; weight loss 6.0% on 3.0 mg, 4.7% on 1.8 mg, 2.0% on placebo. LEADER: 9,340 adults with type 2 diabetes at high cardiovascular risk, median 3.8 years; primary composite outcome 13.0% versus 14.9% (hazard ratio 0.87, 95% CI 0.78 to 0.97), cardiovascular death hazard ratio 0.78, all cause death hazard ratio 0.85.", "animal_evidence": "Rodent and primate pharmacology established GLP-1 receptor mediated reductions in food intake and glucose. Rodent studies showed thyroid C cell tumors at clinically relevant exposures, which is the basis of the boxed warning shared across the class; this finding has not been reproduced in humans.", "conditions": [ "obesity", "type-2-diabetes" ], "literature_dosing": "Weight management (Saxenda label and SCALE): start 0.6 mg subcutaneously once daily, increase by 0.6 mg each week to a maintenance dose of 3.0 mg daily. Type 2 diabetes (Victoza label): 0.6 mg daily for one week, then 1.2 mg daily, with an optional increase to 1.8 mg daily. In SCALE Diabetes both 1.8 mg and 3.0 mg were studied.", "routes": [ "Subcutaneous injection once daily (prefilled pen)" ], "side_effects": [ "Nausea (most common, mild to moderate, peaks during dose escalation)", "Diarrhea", "Constipation", "Vomiting", "Hypoglycemia when combined with insulin or sulfonylureas", "Gallbladder disease including gallstones", "Pancreatitis (rare; incidence was not increased in LEADER)", "Increased heart rate of about 2 to 3 beats per minute", "Boxed warning for thyroid C cell tumors based on rodent data", "Serious adverse events 6.2% versus 5.0% placebo in SCALE" ], "interactions": [ "Insulin and sulfonylureas: increased hypoglycemia risk, dose reduction of those agents is usually needed", "Oral medications: delayed gastric emptying can alter absorption; labels advise monitoring for drugs with a narrow therapeutic window", "Other GLP-1 receptor agonists or GIP/GLP-1 agonists: not studied in combination and not recommended" ], "contraindications": [ "Personal or family history of medullary thyroid carcinoma", "Multiple endocrine neoplasia syndrome type 2", "Prior serious hypersensitivity to liraglutide", "Pregnancy (Saxenda label: discontinue when pregnancy is recognized)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved products (Victoza January 2010, Saxenda December 2014). FDA approved the first generic liraglutide referencing Victoza in December 2024, and generic products referencing Saxenda followed in 2025, so branded, generic, and authorized generic pens are all on the market. FDA listed liraglutide injection as in shortage in its October 2024 and February 2025 GLP-1 updates, and FDA's Drug Shortages database still lists it as of September 27, 2026 (first posted July 18, 2023; updated September 22, 2026), with Victoza and Saxenda presentations at limited availability and unbranded presentations available. FDA states that a compounded drug may not be identical or nearly identical to an FDA-approved drug unless the approved drug is on FDA's drug shortage list. On April 30, 2026 FDA proposed not to include liraglutide on the 503B bulks list; that proposal was not final as of September 2026. Ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "typical_cost": "Manufacturer list price is 1,349.02 USD per month for Saxenda and 543.51 to 815.27 USD per month for Victoza depending on the daily dose (checked 2026-09-22). Generic liraglutide pens cost from about 112 USD per month for the diabetes strength and about 372 USD for the 3 mg weight management generic with a discount card, against average retail prices of about 616 to 924 USD. With commercial insurance the Saxenda savings card can bring a covered prescription to 25 USD. Medicare Part D covers liraglutide for type 2 diabetes but generally not for weight loss alone, and the Medicare GLP-1 Bridge does not include it.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail pharmacy as Victoza, Saxenda, or generic liraglutide.", "Compounded liraglutide: FDA's Drug Shortages database lists liraglutide injection as in shortage as of September 27, 2026, and FDA states that the limit on compounding essentially a copy of an approved drug does not apply to drugs on that list. Generic liraglutide is also marketed. Ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "FDA's Drug Shortages database lists Saxenda (NDC 0169-2800-15) as To Be Discontinued, posted August 25, 2026.", "Products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "Is liraglutide (Saxenda, Victoza) FDA approved and legal?", "a": "Yes. Liraglutide has been FDA approved since January 2010 as Victoza for type 2 diabetes and since December 2014 as Saxenda for chronic weight management. Generic liraglutide referencing Victoza was approved in December 2024 and generics referencing Saxenda followed in 2025. It is prescription only. FDA listed liraglutide injection as in shortage in its October 2024 and February 2025 GLP-1 updates, and FDA's Drug Shortages database still lists it as of September 2026, with Victoza and Saxenda at limited availability. Brand and generic liraglutide are marketed. On April 30, 2026 FDA proposed not to include liraglutide on the 503B bulks list, the list of raw ingredients large outsourcing pharmacies may compound from. Ask any pharmacy offering compounded (custom-made) liraglutide which FDA rule it relies on.", "source_ids": [ "fda-saxenda-label", "fda-first-generics", "fda-glp1-compounding", "fda-glp1-shortage-updates", "fr-2026-08552", "fda-drug-shortages-liraglutide" ] }, { "q": "How much weight do people lose on Saxenda (liraglutide)?", "a": "In the SCALE Obesity and Prediabetes trial of 3,731 adults, the 3.0 mg group lost a mean 8.4 kg over 56 weeks versus 2.8 kg on placebo, a difference of 5.6 kg or roughly 5 percentage points of body weight. About 63% lost at least 5% and 33% lost more than 10%. In people with type 2 diabetes (SCALE Diabetes, n = 846) the loss was smaller at 6.0% versus 2.0%. This is roughly half the effect seen with semaglutide 2.4 mg and a third of tirzepatide 15 mg in their own trials.", "source_ids": [ "scale-obesity", "scale-diabetes" ] }, { "q": "What are the side effects of Saxenda and Victoza?", "a": "Nausea and diarrhea are the most common, usually mild to moderate and worst during dose escalation. Constipation, vomiting, and injection site reactions also occur. Serious risks include gallbladder disease, pancreatitis, and hypoglycemia when used with insulin or sulfonylureas. Heart rate rises by a few beats per minute. The label carries a boxed warning for thyroid C cell tumors seen in rodents. In SCALE, serious adverse events occurred in 6.2% of the liraglutide group versus 5.0% on placebo.", "source_ids": [ "scale-obesity", "fda-saxenda-label" ] }, { "q": "What is the Saxenda and Victoza dose on the FDA label?", "a": "Both are once daily injections under the skin of the abdomen, thigh, or upper arm, at any time of day regardless of meals. Saxenda for weight management starts at 0.6 mg daily and rises by 0.6 mg each week to 3 mg daily; it is approved for adults and for children 12 and older with obesity who weigh more than 60 kg. Victoza for type 2 diabetes starts at 0.6 mg daily for one week, then 1.2 mg, with an optional increase to a 1.8 mg maximum. The daily schedule is the main practical difference from once weekly semaglutide, dulaglutide, and tirzepatide. The prescriber sets the dose.", "source_ids": [ "fda-saxenda-label", "fda-victoza-label" ] }, { "q": "How much do Saxenda, Victoza, and generic liraglutide cost?", "a": "Saxenda lists at 1,349.02 USD per month and Victoza at 543.51 to 815.27 USD per month depending on the dose, but generic liraglutide pens approved since December 2024 cost far less. A published discount-card price source checked 2026-09-22 showed generic pens from about 112 USD per month for the diabetes strength and about 372 USD for the 3 mg weight management strength, against average retail prices of about 616 to 924 USD. The Saxenda savings card can bring a covered commercial prescription to 25 USD. Medicare Part D covers the diabetes indication but generally not weight loss, and the Medicare GLP-1 Bridge does not include liraglutide.", "source_ids": [ "price-list-diabetes", "price-list-weight", "price-savings-weight", "price-cash-generic-diabetes", "price-cash-generic-weight", "fda-first-generics", "medicare-glp1-bridge" ] }, { "q": "Is liraglutide banned by WADA?", "a": "No. GLP-1 receptor agonists including liraglutide are not on the WADA Prohibited List as of the 2026 list or the 2027 list published in September 2026. Athletes should still confirm any therapeutic use exemption requirements with their anti-doping organization, and the list is updated every January.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "Saxenda vs Wegovy: which is better?", "a": "Semaglutide produces more weight loss and needs only weekly injections. Liraglutide 3.0 mg produced about 8% weight loss at 56 weeks in SCALE, versus about 15% for semaglutide 2.4 mg at 68 weeks in STEP 1, and in the cagrilintide phase 2 trial liraglutide 3.0 mg (9.0%) was also beaten by cagrilintide 4.5 mg (10.8%). Liraglutide's advantages are that it is now generic and cheaper, has the longest safety record in the class, and its daily dosing lets a provider stop it quickly if side effects appear. Both have cardiovascular outcome data (LEADER for liraglutide).", "source_ids": [ "scale-obesity", "cagrilintide-phase2", "leader" ] }, { "q": "Does Victoza (liraglutide) protect the heart?", "a": "Yes, in people with type 2 diabetes. In LEADER, 9,340 adults with type 2 diabetes at high cardiovascular risk were followed for a median of 3.8 years; the composite of cardiovascular death, nonfatal heart attack, or nonfatal stroke occurred in 13.0% on liraglutide versus 14.9% on placebo (hazard ratio 0.87). Cardiovascular death (hazard ratio 0.78) and all cause death (hazard ratio 0.85) were also lower. Victoza carries an indication to reduce major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.", "source_ids": [ "leader", "fda-victoza-label" ] } ], "studies": [ { "pmid": "26132939", "title": "A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes)", "year": 2015, "design": "Randomized, double blind, placebo controlled trial, 56 weeks", "n": 3731, "population": "Adults without diabetes with BMI 30 or higher, or 27 or higher with dyslipidemia or hypertension", "outcome": "Mean weight loss 8.4 kg with liraglutide 3.0 mg versus 2.8 kg with placebo; 63.2% versus 27.1% lost at least 5%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26132939/" }, { "pmid": "26284720", "title": "Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes randomized clinical trial", "year": 2015, "design": "Randomized, double blind, placebo controlled trial, 56 weeks", "n": 846, "population": "Adults with type 2 diabetes and BMI 27 or higher on 0 to 3 oral agents", "outcome": "Weight loss 6.0% with 3.0 mg, 4.7% with 1.8 mg, 2.0% with placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26284720/" }, { "pmid": "27295427", "title": "Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER)", "year": 2016, "design": "Randomized, double blind, placebo controlled cardiovascular outcomes trial, median 3.8 years", "n": 9340, "population": "Adults with type 2 diabetes at high cardiovascular risk", "outcome": "Major adverse cardiovascular events 13.0% versus 14.9% (hazard ratio 0.87, 95% CI 0.78 to 0.97); cardiovascular death hazard ratio 0.78", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27295427/" }, { "pmid": "34798060", "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial (liraglutide 3.0 mg active comparator)", "year": 2021, "design": "Randomized, double blind, placebo and active controlled dose finding trial, 26 weeks", "n": 706, "population": "Adults without diabetes with BMI 30 or higher, or 27 or higher with a comorbidity", "outcome": "Liraglutide 3.0 mg produced 9.0% weight loss versus 10.8% with cagrilintide 4.5 mg and 3.0% with placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/" } ], "sources": [ { "id": "scale-obesity", "type": "pubmed", "title": "Pi-Sunyer X et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015 (SCALE Obesity and Prediabetes)", "url": "https://pubmed.ncbi.nlm.nih.gov/26132939/", "pmid": "26132939", "year": 2015 }, { "id": "scale-diabetes", "type": "pubmed", "title": "Davies MJ et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes randomized clinical trial. JAMA 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26284720/", "pmid": "26284720", "year": 2015 }, { "id": "leader", "type": "pubmed", "title": "Marso SP et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016 (LEADER)", "url": "https://pubmed.ncbi.nlm.nih.gov/27295427/", "pmid": "27295427", "year": 2016 }, { "id": "cagrilintide-phase2", "type": "pubmed", "title": "Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial. Lancet 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/", "pmid": "34798060", "year": 2021 }, { "id": "fda-saxenda-label", "type": "fda", "title": "FDA prescribing information for Saxenda (liraglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=saxenda", "year": 2025 }, { "id": "fda-victoza-label", "type": "fda", "title": "FDA prescribing information for Victoza (liraglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=victoza", "year": 2025 }, { "id": "fda-first-generics", "type": "fda", "title": "FDA: First generic drug approvals (includes liraglutide injection, December 2024)", "url": "https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals", "year": 2025 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss, including shortage resolution and compounding deadlines", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-list-diabetes", "type": "other", "title": "Manufacturer list price (wholesale acquisition cost) page for liraglutide for type 2 diabetes, 2-pen and 3-pen packs, accessed 2026-09-22", "url": "https://www.novopricing.com/victoza.html", "year": 2026 }, { "id": "price-list-weight", "type": "other", "title": "Manufacturer list price (wholesale acquisition cost) page for liraglutide 3 mg for weight management, accessed 2026-09-22", "url": "https://www.novopricing.com/saxenda.html", "year": 2026 }, { "id": "price-savings-weight", "type": "other", "title": "Manufacturer list price and savings card explainer for liraglutide 3 mg for weight management, accessed 2026-09-22", "url": "https://www.novocare.com/obesity/products/saxenda/explaining-list-price.html", "year": 2026 }, { "id": "price-cash-generic-diabetes", "type": "other", "title": "Published cash-price comparison for generic liraglutide 18 mg/3 mL pens (diabetes strength), discount-card and average retail prices, accessed 2026-09-22", "url": "https://www.goodrx.com/liraglutide-victoza", "year": 2026 }, { "id": "price-cash-generic-weight", "type": "other", "title": "Published cash-price comparison for generic liraglutide 3 mg pens (weight management), discount-card and average retail prices, accessed 2026-09-22", "url": "https://www.goodrx.com/liraglutide-saxenda", "year": 2026 }, { "id": "medicare-glp1-bridge", "type": "other", "title": "Medicare.gov: weight loss drugs, Medicare GLP-1 Bridge coverage, eligibility, and 50 USD copay, accessed 2026-09-22", "url": "https://www.medicare.gov/coverage/weight-loss-drugs", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 }, { "id": "fda-glp1-shortage-updates", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (GLP-1 shortage status updates, including liraglutide, and the April 1, 2026 policy update on essentially copies)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "year": 2026 }, { "id": "fr-2026-08552", "type": "federal_register", "title": "Federal Register 2026-08552: List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B (proposed May 1, 2026; comments extended to July 30, 2026)", "url": "https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal", "year": 2026 }, { "id": "fda-drug-shortages-liraglutide", "type": "fda", "title": "FDA Drug Shortages: liraglutide injection (currently in shortage; checked September 27, 2026)", "url": "https://dps.fda.gov/drugshortages/activeingredient/liraglutide-injection", "year": 2026 } ], "related": [ "semaglutide", "tirzepatide", "dulaglutide", "cagrilintide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Liraglutide (Saxenda, Victoza): evidence and access", "description": "Saxenda and Victoza are both liraglutide, now also sold as a generic. Trial weight loss, side effects, FDA label doses, heart data, cost, and legal status.", "h1": "Liraglutide (Saxenda, Victoza)", "headings": { "safety": "Saxenda and Victoza side effects in trials" } } }, { "slug": "retatrutide", "name": "Retatrutide", "aliases": [ "LY3437943", "triple agonist", "GIP/GLP-1/glucagon triple receptor agonist", "reta", "reta peptide", "GLP-3", "GLP-3 peptide" ], "class": "Investigational triple agonist of the GIP, GLP-1, and glucagon receptors (single acylated peptide, once weekly)", "one_liner": "Investigational triple agonist, nicknamed reta or GLP-3, with 24.2% weight loss at 48 weeks in phase 2 and 28.3% in a phase 3 topline; not FDA approved.", "summary": "Retatrutide is an investigational (still in clinical trials) once weekly injected peptide that activates three hormone receptors at once, GIP, GLP-1, and glucagon; online it is nicknamed \"reta\" or \"GLP-3\", but there is no GLP-3 hormone, and the nickname only reflects its three targets. In a 48 week phase 2 trial of 338 adults with obesity, the 12 mg dose produced a mean 24.2% weight loss versus 2.1% on placebo, and the manufacturer's TRIUMPH-1 phase 3 topline release reported 28.3% at 80 weeks. As of September 2026 it is not FDA approved or approved anywhere else, cannot lawfully be compounded (custom-made by a pharmacy), and is prohibited in sport under WADA section S0.", "mechanism": "Retatrutide is a single peptide engineered to activate three receptors. GLP-1 receptor activation reduces appetite, slows gastric emptying, and increases glucose dependent insulin release. GIP receptor activation adds appetite and insulin effects. Glucagon receptor activation increases energy expenditure and liver fat oxidation, which is thought to explain the larger weight loss than GLP-1 or GIP/GLP-1 agonists alone, at the cost of a small rise in heart rate. It is acylated for a roughly one week half life.", "evidence_grade": "human_rct", "evidence_summary": "Phase 2 randomized controlled trials in obesity (n = 338, 48 weeks) and type 2 diabetes (n = 281, 36 weeks) plus a phase 3 type 2 diabetes trial (TRANSCEND-T2D-1, n = 537, 40 weeks) published in 2026. In the obesity trial, weight loss at 48 weeks was 8.7%, 17.1%, 22.8%, and 24.2% at 1, 4, 8, and 12 mg versus 2.1% on placebo. Phase 3 obesity trials (TRIUMPH) have reported topline results by company press release, including 28.3% at 80 weeks in TRIUMPH-1 and 28.7% at 68 weeks in TRIUMPH-4, not yet peer reviewed. No cardiovascular outcomes trial has reported.", "human_evidence": "Phase 2 obesity trial: 338 adults with BMI 30 or higher (or 27 to 30 with a weight related condition), 48 weeks; least squares mean weight change minus 8.7% (1 mg), minus 17.1% (4 mg), minus 22.8% (8 mg), minus 24.2% (12 mg) versus minus 2.1% (placebo). At 12 mg, 100% lost at least 5%, 93% at least 10%, and 83% at least 15%. Phase 2 type 2 diabetes trial: 281 adults, 36 weeks, retatrutide up to 12 mg versus placebo and dulaglutide 1.5 mg, with clinically meaningful HbA1c and weight reductions; a DXA substudy showed most of the weight lost was fat mass. TRANSCEND-T2D-1: 537 adults with type 2 diabetes on diet and exercise alone, 40 weeks, retatrutide 4, 9, or 12 mg versus placebo, with significant improvements in glycemic control and weight.", "animal_evidence": "Preclinical rodent and primate pharmacology established the triple receptor binding profile and the additive effect of glucagon receptor agonism on energy expenditure. Thyroid C cell findings in rodents are expected to apply as with other GLP-1 based agonists; formal labeling has not been issued because the drug is not approved.", "conditions": [ "obesity", "type-2-diabetes" ], "literature_dosing": "Phase 2 obesity trial: once weekly subcutaneous injection escalated to maintenance doses of 1, 4, 8, or 12 mg, with starting doses of 2 or 4 mg and escalation every 4 weeks. Phase 3 type 2 diabetes trial: 4, 9, or 12 mg weekly. No approved label exists; these are trial regimens only.", "routes": [ "Subcutaneous injection once weekly (clinical trials only)" ], "side_effects": [ "Nausea, diarrhea, vomiting, and constipation (dose related, mostly mild to moderate, partly mitigated by lower starting dose)", "Increased heart rate, greater than with GLP-1 only agonists, attributed to glucagon receptor activity", "Dysesthesia (abnormal skin sensation) in 12.5% on 12 mg versus 0.9% on placebo in the TRIUMPH-1 topline release", "Skin sensitivity and dysesthesia reported in the phase 2 trial", "Decreased appetite", "Long term safety not established; no cardiovascular outcomes trial reported as of last verification" ], "interactions": [ "No approved label, so no formal interaction studies are published", "Class effects expected: hypoglycemia with insulin or sulfonylureas, and altered absorption of oral drugs from delayed gastric emptying", "Should not be combined with other GLP-1 based agonists (not studied)" ], "contraindications": [ "Not approved for any use; only available inside registered clinical trials", "Personal or family history of medullary thyroid carcinoma or MEN2 (trial exclusion criteria, class precaution)", "Pregnancy and breastfeeding (excluded from trials)", "Competitive athletes subject to WADA testing (prohibited under S0)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved and not approved by any other regulator as of the last verification date. Because retatrutide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded by 503A pharmacies or 503B outsourcing facilities. FDA has warned that unapproved GLP-1 class products sold online, including investigational molecules, are not evaluated for safety, quality, or dose. Any product sold as retatrutide outside a clinical trial is unlawful for human use.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B while investigational.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is retatrutide legal?", "a": "Not for sale or prescription. Retatrutide is investigational and not approved by FDA or any other regulator as of September 2026, and the manufacturer says it is legally available only to participants in its clinical trials. It cannot be compounded because it is not a component of an approved drug and is not on any FDA bulks list. Products sold online as retatrutide are unapproved drugs with no verification of identity or dose.", "source_ids": [ "triumph-1-topline", "fda-glp1-compounding", "fda-503a-bulks" ] }, { "q": "Why is retatrutide called reta or GLP-3?", "a": "Reta is shorthand for retatrutide. GLP-3 is an online nickname, not a scientific name: there is no hormone called GLP-3. The nickname points to its three targets, since retatrutide activates the GIP, GLP-1, and glucagon receptors, one more than tirzepatide and two more than semaglutide. Trial papers call it retatrutide or by its development code, LY3437943.", "source_ids": [ "retatrutide-discovery", "triumph-design" ] }, { "q": "Retatrutide before and after: what did the trials measure?", "a": "Trials measured average change in body weight, not individual photos. In the phase 2 trial of 338 adults, mean weight change at 48 weeks was minus 24.2% on 12 mg versus minus 2.1% on placebo, and 83% on 12 mg lost at least 15%. In the TRIUMPH-1 phase 3 topline release, adults without diabetes on 12 mg lost 28.3% at 80 weeks versus 2.2% on placebo, and in TRIUMPH-4, adults with knee osteoarthritis lost 28.7% at 68 weeks. In type 2 diabetes (TRANSCEND-T2D-1), weight fell 11.5% to 15.3% at 40 weeks versus 2.6%. The phase 3 obesity figures are company releases, not yet peer reviewed.", "source_ids": [ "retatrutide-phase2-obesity", "triumph-1-topline", "triumph-4-topline", "transcend-t2d-1" ] }, { "q": "What safety signals did retatrutide trials report?", "a": "Gastrointestinal effects dominate, as with other GLP-1 based drugs. In the TRIUMPH-1 topline release, nausea affected 42.4% on 12 mg versus 14.8% on placebo, with diarrhea, constipation, and vomiting also common. Dysesthesia, an abnormal skin sensation, occurred in 12.5% on 12 mg versus 0.9% on placebo, and 11.3% on 12 mg stopped for adverse events versus 4.9% on placebo. Heart rate rises more than with GLP-1 only drugs because of the glucagon activity. Long term safety and cardiovascular outcomes are not yet known.", "source_ids": [ "triumph-1-topline", "retatrutide-phase2-obesity" ] }, { "q": "Is retatrutide an injection or a pill?", "a": "An injection. Every published phase 2 and phase 3 trial gave retatrutide as a once weekly injection under the skin, and no oral version has been tested in a published trial. Products sold online as retatrutide capsules, drops, or pills are unapproved and unverified, and FDA has warned about unapproved GLP-1 products sold online. Among approved weight management drugs, semaglutide is available as a daily tablet (Wegovy tablets).", "source_ids": [ "retatrutide-phase2-obesity", "triumph-design", "fda-glp1-compounding", "fda-wegovy-label" ] }, { "q": "How long does retatrutide stay in your system?", "a": "Its half life was about 6 days in a phase 1b trial, which is what allows once weekly dosing. Blood levels fall by roughly half every 6 days after a last dose, so it takes several weeks to clear, and in the first single dose study weight reduction persisted up to day 43 after one injection. No approved label exists, so there is no official guidance on stopping before surgery or pregnancy.", "source_ids": [ "retatrutide-phase1b", "retatrutide-discovery" ] }, { "q": "Retatrutide vs tirzepatide: what is the difference?", "a": "Tirzepatide (Zepbound, Mounjaro) activates two receptors (GIP and GLP-1) and is FDA approved; retatrutide adds a third (glucagon) and is investigational. In their separate trials, retatrutide 12 mg produced 24.2% weight loss at 48 weeks in phase 2 versus tirzepatide 15 mg at 20.9% over 72 weeks, and no head-to-head trial exists. Retatrutide raises heart rate more because of its glucagon activity. Until FDA reviews the phase 3 data and approves it, tirzepatide is the only one of the two a patient can lawfully be prescribed.", "source_ids": [ "retatrutide-phase2-obesity", "fda-glp1-compounding" ] } ], "studies": [ { "pmid": "37366315", "title": "Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial", "year": 2023, "design": "Randomized, double blind, placebo controlled phase 2 trial, 48 weeks", "n": 338, "population": "Adults with BMI 30 or higher, or 27 to less than 30 with a weight related condition, without diabetes", "outcome": "Mean weight change at 48 weeks minus 8.7% (1 mg), minus 17.1% (4 mg), minus 22.8% (8 mg), minus 24.2% (12 mg) versus minus 2.1% (placebo)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/" }, { "pmid": "37385280", "title": "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial", "year": 2023, "design": "Randomized, double blind, placebo and active (dulaglutide) controlled phase 2 trial, 36 weeks", "n": 281, "population": "Adults with type 2 diabetes on diet and exercise or stable metformin", "outcome": "Clinically meaningful HbA1c and body weight reductions versus placebo and dulaglutide 1.5 mg; safety consistent with GLP-1 class", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/" }, { "pmid": "42250575", "title": "Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a phase 3 trial", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 3 trial, 40 weeks", "n": 537, "population": "Adults with type 2 diabetes inadequately controlled by diet and exercise alone", "outcome": "Significant improvements in glycemic control and body weight at 4, 9, and 12 mg weekly versus placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42250575/" }, { "pmid": "36354040", "title": "LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b multiple-ascending dose trial", "year": 2022, "design": "Phase 1b randomized, double-blind, placebo-controlled multiple ascending dose trial, 12 weeks", "n": 72, "population": "Adults with type 2 diabetes", "outcome": "Half life about 6 days, supporting once weekly dosing; dose dependent reductions in glucose, HbA1c, and body weight; gastrointestinal events most common", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36354040/" } ], "sources": [ { "id": "retatrutide-phase2-obesity", "type": "pubmed", "title": "Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/", "pmid": "37366315", "year": 2023 }, { "id": "retatrutide-phase2-t2d", "type": "pubmed", "title": "Rosenstock J et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial. Lancet 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/", "pmid": "37385280", "year": 2023 }, { "id": "transcend-t2d-1", "type": "pubmed", "title": "Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial. Lancet 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42250575/", "pmid": "42250575", "year": 2026 }, { "id": "triumph-design", "type": "pubmed", "title": "Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41090431/", "pmid": "41090431", "year": 2026 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "triumph-1-topline", "type": "other", "title": "Manufacturer press release: topline results of the TRIUMPH-1 phase 3 trial of retatrutide (May 21, 2026), not peer reviewed", "url": "https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss", "year": 2026 }, { "id": "triumph-4-topline", "type": "other", "title": "Manufacturer press release: topline results of the TRIUMPH-4 phase 3 trial of retatrutide in obesity and knee osteoarthritis (December 11, 2025), not peer reviewed", "url": "https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average", "year": 2025 }, { "id": "retatrutide-phase1b", "type": "pubmed", "title": "Urva S et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36354040/", "pmid": "36354040", "year": 2022 }, { "id": "retatrutide-discovery", "type": "pubmed", "title": "Coskun T et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35985340/", "pmid": "35985340", "year": 2022 }, { "id": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection and tablets, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" } ], "related": [ "tirzepatide", "semaglutide", "survodutide", "mazdutide" ], "cluster": "glp1", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "What is retatrutide (GLP-3)? Trial results and legality", "description": "Retatrutide, nicknamed GLP-3, is an experimental triple GIP, GLP-1, and glucagon receptor agonist. Trial weight loss, safety, and legal status.", "h1": "Retatrutide (reta, GLP-3)", "headings": { "summary": "What is retatrutide?", "safety": "Retatrutide safety in trials: a summary", "access": "Can you get retatrutide legally?" } } }, { "slug": "cagrilintide", "name": "Cagrilintide", "aliases": [ "AM833", "NN9838", "CagriSema (with semaglutide)", "long acting amylin analog", "cagrilintide semaglutide", "Cagri-Sema" ], "class": "Investigational long acting amylin analog (acylated, once weekly), developed alone and in fixed combination with semaglutide 2.4 mg", "one_liner": "Experimental weekly copy of the appetite hormone amylin: 10.8% weight loss alone at 26 weeks and 20.4% with semaglutide at 68 weeks; not FDA approved.", "summary": "Cagrilintide is an investigational (still in trials) once weekly amylin analog, a lab-made version of a pancreas hormone that reduces appetite through a different pathway from GLP-1 drugs, and it is being developed mainly as CagriSema, a fixed combination with semaglutide 2.4 mg. Alone it produced 10.8% weight loss at 4.5 mg over 26 weeks in a phase 2 trial of 706 people, and CagriSema produced 20.4% weight loss at 68 weeks in adults without diabetes (REDEFINE 1, 3,417 people) and 13.7% in adults with type 2 diabetes (REDEFINE 2, 1,206 people). As of September 2026 neither form is FDA approved, neither can lawfully be compounded (custom-made by a pharmacy), and cagrilintide is prohibited in sport under WADA section S0, the anti-doping ban on unapproved substances.", "mechanism": "Cagrilintide is an analog of amylin, a hormone co-secreted with insulin by pancreatic beta cells. It activates amylin receptors and calcitonin receptors in the area postrema and hypothalamus, slowing gastric emptying, suppressing glucagon, and increasing satiety. Because this pathway is separate from GLP-1 signaling, combining it with semaglutide produces additive weight loss. A fatty acid side chain binds albumin for once weekly dosing.", "evidence_grade": "human_rct", "evidence_summary": "One phase 2 monotherapy trial (n = 706, 26 weeks) and a phase 3 program for the semaglutide combination. Alone, cagrilintide 0.3 to 4.5 mg produced 6.0% to 10.8% weight loss versus 3.0% on placebo. In REDEFINE 1 (n = 3,417, 68 weeks) the combination produced 20.4% weight loss versus 3.0% on placebo; in REDEFINE 2 (n = 1,206, 68 weeks, type 2 diabetes) 13.7% versus 3.4%; and in REDEFINE 5 (n = 331, East Asia) it beat semaglutide alone by 6.5 percentage points. In the open label REDEFINE 4 trial (n = 809, 84 weeks) the combination produced 23.0% weight loss versus 25.5% with tirzepatide 15 mg and missed non-inferiority (manufacturer topline, not peer reviewed). In type 2 diabetes, three published phase 3 trials support the combination: REIMAGINE 2 (n = 2,713, 68 weeks, on metformin with or without an SGLT2 inhibitor) found it superior to semaglutide 2.4 mg alone on HbA1c (minus 1.91 versus minus 1.75 points); REIMAGINE 1 (n = 189, 40 weeks, not controlled by diet and exercise alone) showed HbA1c minus 1.8 versus minus 0.1 points and weight minus 13.8% versus minus 1.4% on placebo; and REIMAGINE 3 (n = 274, 40 weeks, added to basal insulin) showed HbA1c minus 2.33 versus minus 0.66 points with 10% to 12% weight loss. An earlier phase 2 trial (n = 92, 32 weeks) showed similar direction of effect.", "human_evidence": "Phase 2 monotherapy (Lau 2021): 706 adults without diabetes with BMI 30 or higher (or 27 with a comorbidity), 26 weeks; weight loss 6.0% to 10.8% across 0.3 to 4.5 mg versus 3.0% on placebo, and 10.8% with 4.5 mg versus 9.0% with liraglutide 3.0 mg. REDEFINE 1 (Garvey 2025): 3,417 adults without diabetes, 68 weeks; estimated mean weight change minus 20.4% with cagrilintide 2.4 mg plus semaglutide 2.4 mg versus minus 3.0% with placebo (difference 17.3 percentage points). REDEFINE 5 (2026): 331 adults in Japan and Taiwan, 68 weeks; minus 18.4% with the combination versus minus 11.9% with semaglutide alone. Phase 2 type 2 diabetes (Frias 2023): 92 adults, 32 weeks, clinically relevant HbA1c improvement with the combination.", "animal_evidence": "Rodent pharmacology established amylin receptor mediated reductions in food intake and body weight and the additive effect with GLP-1 receptor agonists. No labeling exists because the drug is not approved.", "conditions": [ "obesity", "type-2-diabetes" ], "literature_dosing": "Monotherapy phase 2: once weekly subcutaneous cagrilintide escalated to maintenance doses of 0.3, 0.6, 1.2, 2.4, or 4.5 mg. Phase 3 combination: cagrilintide 2.4 mg plus semaglutide 2.4 mg once weekly after a 16 week escalation. No approved label exists; these are trial regimens only.", "routes": [ "Subcutaneous injection once weekly (clinical trials only)" ], "side_effects": [ "Nausea (20% to 47% across cagrilintide doses versus 18% placebo in phase 2)", "Gastrointestinal adverse events overall 41% to 63% versus 32% placebo in phase 2", "Constipation and diarrhea", "Injection site reactions", "In combination with semaglutide, gastrointestinal events in about half of participants (53% in REDEFINE 5)", "Long term safety and cardiovascular outcomes not yet reported" ], "interactions": [ "No approved label, so no formal interaction studies are published", "Delayed gastric emptying may alter absorption of oral drugs (amylin class effect, also seen with pramlintide)", "Hypoglycemia risk when combined with insulin or sulfonylureas in people with diabetes (class precaution)" ], "contraindications": [ "Not approved for any use; only available inside registered clinical trials", "Pregnancy and breastfeeding (excluded from trials)", "Competitive athletes subject to WADA testing (prohibited under S0)", "When combined with semaglutide, the semaglutide contraindications (medullary thyroid carcinoma, MEN2) apply" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved as of the last verification date, either alone or in the fixed combination with semaglutide. Because cagrilintide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded. Any product sold as cagrilintide or CagriSema outside a clinical trial is an unapproved drug. Check FDA for the status of any marketing application before relying on this record.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B while investigational.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is cagrilintide or CagriSema FDA approved?", "a": "No. Cagrilintide is investigational and not approved by FDA as of September 2026, alone or combined with semaglutide (CagriSema). The manufacturer submitted a new drug application (the formal request for FDA approval) for the combination in December 2025; a submission is not an approval. Neither form can be compounded (custom-made by a pharmacy), because cagrilintide is not a component of an approved product and is not on any FDA bulks list, so the only lawful access is a registered clinical trial. Products sold online as cagrilintide are unapproved drugs with no verification of identity or dose, and none has a lawful price.", "source_ids": [ "cagrisema-nda", "fda-glp1-compounding", "fda-503a-bulks" ] }, { "q": "What is CagriSema?", "a": "CagriSema is the development name for cagrilintide 2.4 mg and semaglutide 2.4 mg given together once weekly in one injection. It pairs an amylin analog with the GLP-1 drug in Wegovy, two appetite pathways at once. In the 68 week REDEFINE 1 trial of 3,417 adults without diabetes, it produced 20.4% weight loss versus 3.0% on placebo. It is investigational: the manufacturer filed for FDA approval in December 2025, and no approval had been granted as of September 2026.", "source_ids": [ "redefine-1", "cagrisema-nda" ] }, { "q": "How much weight do people lose on cagrilintide?", "a": "Alone, in the 26 week phase 2 trial of 706 adults, weight loss ranged from 6.0% at 0.3 mg to 10.8% at 4.5 mg versus 3.0% on placebo, and 4.5 mg beat liraglutide 3.0 mg (9.0%). Combined with semaglutide 2.4 mg in REDEFINE 1, a 68 week phase 3 trial of 3,417 adults, the estimated mean weight loss was 20.4% versus 3.0% on placebo. In the East Asian REDEFINE 5 trial the combination beat semaglutide alone by 6.5 percentage points (18.4% versus 11.9%).", "source_ids": [ "cagrilintide-phase2", "redefine-1", "redefine-5" ] }, { "q": "What are the side effects of cagrilintide?", "a": "Mostly gastrointestinal. In the phase 2 monotherapy trial, 41% to 63% of cagrilintide participants had gastrointestinal adverse events versus 32% on placebo, mainly nausea (20% to 47% versus 18%), plus constipation, diarrhea, and injection site reactions. With semaglutide in REDEFINE 2, 72.5% reported gastrointestinal events versus 34.4% on placebo, most transient and mild or moderate. Long term safety and cardiovascular outcomes have not been reported.", "source_ids": [ "cagrilintide-phase2", "redefine-2", "redefine-5" ] }, { "q": "Does CagriSema help type 2 diabetes?", "a": "Phase 3 data say it lowers weight and blood sugar. In REDEFINE 2, 1,206 adults with type 2 diabetes and overweight or obesity lost 13.7% of body weight at 68 weeks on cagrilintide 2.4 mg plus semaglutide 2.4 mg versus 3.4% on placebo, and 73.5% reached an HbA1c of 6.5% or less versus 15.9%. An earlier 32 week phase 2 trial of 92 adults found better glucose control with the combination than with either drug alone. It is not approved for diabetes.", "source_ids": [ "redefine-2", "cagrisema-t2d-phase2" ] }, { "q": "Cagrilintide vs semaglutide: what is the difference?", "a": "They work on different pathways. Semaglutide is an approved GLP-1 receptor agonist; cagrilintide is an investigational amylin analog. Alone, cagrilintide 4.5 mg produced 10.8% weight loss at 26 weeks, less than semaglutide 2.4 mg at 68 weeks (about 15%), but the two together (CagriSema) reached 20.4% in REDEFINE 1 and beat semaglutide alone by 6.5 points in REDEFINE 5. The combination is the product in development, not cagrilintide by itself.", "source_ids": [ "cagrilintide-phase2", "redefine-1", "redefine-5" ] }, { "q": "Is cagrilintide banned by WADA?", "a": "Yes. Cagrilintide has no approval from any government health authority, so it is prohibited at all times under section S0 (non-approved substances) of the WADA Prohibited List. This differs from approved GLP-1 agonists, which are not prohibited.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "34798060", "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial", "year": 2021, "design": "Randomized, double blind, placebo and active (liraglutide 3.0 mg) controlled dose finding trial, 26 weeks", "n": 706, "population": "Adults without diabetes with BMI 30 or higher, or 27 or higher with a comorbidity", "outcome": "Weight loss 6.0% to 10.8% across 0.3 to 4.5 mg versus 3.0% placebo; 4.5 mg beat liraglutide 3.0 mg (10.8% versus 9.0%)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/" }, { "pmid": "40544433", "title": "Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1)", "year": 2025, "design": "Randomized, double blind, placebo and active controlled phase 3a trial, 68 weeks", "n": 3417, "population": "Adults without diabetes with BMI 30 or higher, or 27 or higher with a complication", "outcome": "Estimated mean weight change minus 20.4% with cagrilintide 2.4 mg plus semaglutide 2.4 mg versus minus 3.0% placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/" }, { "pmid": "42009015", "title": "Co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity in Japan and Taiwan (REDEFINE 5)", "year": 2026, "design": "Randomized, double blind, active controlled phase 3a trial, 68 weeks", "n": 331, "population": "Adults in Japan and Taiwan with BMI 27 or higher, with or without type 2 diabetes", "outcome": "Weight change minus 18.4% with the combination versus minus 11.9% with semaglutide alone (difference minus 6.5 percentage points)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42009015/" }, { "pmid": "37364590", "title": "Co-administered once-weekly cagrilintide 2.4 mg with semaglutide 2.4 mg in type 2 diabetes: a phase 2 trial", "year": 2023, "design": "Randomized, double blind, active controlled phase 2 trial, 32 weeks", "n": 92, "population": "Adults with type 2 diabetes and BMI 27 or higher", "outcome": "Clinically relevant improvements in HbA1c and continuous glucose monitoring measures with the combination versus each drug alone", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37364590/" }, { "pmid": "40544432", "title": "Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2)", "year": 2025, "design": "Phase 3 randomized, double-blind, placebo-controlled trial, 68 weeks", "n": 1206, "population": "Adults with overweight or obesity and type 2 diabetes", "outcome": "Mean body weight change minus 13.7% with cagrilintide 2.4 mg plus semaglutide 2.4 mg versus minus 3.4% with placebo; HbA1c of 6.5% or less in 73.5% versus 15.9%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/40544432/" }, { "pmid": "42251859", "title": "Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2)", "year": 2026, "design": "Randomized, double blind, placebo and active controlled phase 3 trial, 68 weeks", "n": 2713, "population": "Adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor and BMI 25 or higher", "outcome": "HbA1c change minus 1.91 points with cagrilintide and semaglutide 2.4 mg each versus minus 1.75 with semaglutide 2.4 mg alone (superior)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42251859/" }, { "pmid": "42251860", "title": "Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1)", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 3a trial, 40 weeks", "n": 189, "population": "Adults with type 2 diabetes not controlled by diet and exercise alone", "outcome": "HbA1c minus 1.8 versus minus 0.1 points and body weight minus 13.8% versus minus 1.4% on placebo (efficacy estimand)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42251860/" }, { "pmid": "42251856", "title": "Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3)", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 3a trial, 40 weeks", "n": 274, "population": "Adults with type 2 diabetes on stable basal insulin with or without metformin", "outcome": "HbA1c minus 2.33 points (2.4 mg each) versus minus 0.66 on placebo (efficacy estimand), with 10% to 12% weight loss on the combination", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42251856/" } ], "sources": [ { "id": "cagrilintide-phase2", "type": "pubmed", "title": "Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial. Lancet 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/", "pmid": "34798060", "year": 2021 }, { "id": "redefine-1", "type": "pubmed", "title": "Garvey WT et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. N Engl J Med 2025 (REDEFINE 1)", "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/", "pmid": "40544433", "year": 2025 }, { "id": "redefine-5", "type": "pubmed", "title": "Yamauchi T et al. Co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity in Japan and Taiwan (REDEFINE 5). Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42009015/", "pmid": "42009015", "year": 2026 }, { "id": "cagrisema-t2d-phase2", "type": "pubmed", "title": "Frias JP et al. Co-administered once-weekly cagrilintide 2.4 mg with semaglutide 2.4 mg in type 2 diabetes: a phase 2 trial. Lancet 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37364590/", "pmid": "37364590", "year": 2023 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "redefine-2", "type": "pubmed", "title": "Davies MJ et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes. N Engl J Med 2025 (REDEFINE 2)", "url": "https://pubmed.ncbi.nlm.nih.gov/40544432/", "pmid": "40544432", "year": 2025 }, { "id": "cagrisema-nda", "type": "other", "title": "Manufacturer press release: new drug application submitted to FDA for once weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg (December 18, 2025), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp1-and-amylin-analogues-for-weight-management-302645862.html", "year": 2025 }, { "id": "redefine-4-topline", "type": "other", "title": "Manufacturer company announcement: REDEFINE 4 headline results (February 23, 2026), not peer reviewed", "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916501", "year": 2026 }, { "id": "reimagine-2", "type": "pubmed", "title": "Buse JB et al. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2). Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42251859/", "pmid": "42251859", "year": 2026 }, { "id": "reimagine-1", "type": "pubmed", "title": "Aroda VR et al. Once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1). Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42251860/", "pmid": "42251860", "year": 2026 }, { "id": "reimagine-3", "type": "pubmed", "title": "Rosenstock J et al. Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3). Lancet 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42251856/", "pmid": "42251856", "year": 2026 } ], "related": [ "semaglutide", "liraglutide", "pramlintide", "retatrutide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Cagrilintide: trial results and regulatory status", "description": "Cagrilintide alone and as CagriSema with semaglutide: REDEFINE phase 3 weight loss, type 2 diabetes results, side effects, and FDA and WADA status.", "h1": "Cagrilintide (and CagriSema)" } }, { "slug": "dulaglutide", "name": "Dulaglutide", "aliases": [ "Trulicity", "LY2189265", "GLP-1 Fc fusion" ], "class": "GLP-1 receptor agonist (two modified GLP-1 analogs fused to a human IgG4 Fc fragment, once weekly)", "one_liner": "FDA approved weekly GLP-1 drug for type 2 diabetes that cut heart attacks, strokes, and heart deaths by 12% over 5.4 years in REWIND; not for weight loss.", "summary": "Dulaglutide is an FDA approved once weekly GLP-1 receptor agonist (a drug that mimics GLP-1, a gut hormone that boosts insulin and curbs appetite) sold as Trulicity for type 2 diabetes since 2014, including in children 10 and older since 2022. In the REWIND trial of 9,901 adults it reduced major adverse cardiovascular events (heart attack, stroke, or cardiovascular death) by 12% over a median 5.4 years, the longest follow up of any GLP-1 outcomes trial. It lowers HbA1c (a measure of average blood sugar over about 3 months) by about 1.5 to 1.9 percentage points and causes modest weight loss (3 to 5 kg), but it is not approved for weight management.", "mechanism": "Dulaglutide consists of two GLP-1 analog chains linked to a modified human IgG4 Fc fragment, which gives a half life of about 5 days. It activates the GLP-1 receptor to increase glucose dependent insulin secretion, suppress glucagon, slow gastric emptying, and reduce appetite. The large Fc fusion means it is a much bigger molecule than semaglutide or liraglutide, which affects how it distributes but not its receptor pharmacology.", "evidence_grade": "human_rct", "evidence_summary": "Large randomized controlled trials in type 2 diabetes. REWIND (n = 9,901, median 5.4 years) showed a hazard ratio of 0.88 for major adverse cardiovascular events. AWARD-11 (n = 1,842, 52 weeks) showed that 3.0 mg and 4.5 mg doses lower HbA1c and weight more than 1.5 mg. In head to head trials it has served as an active comparator that was beaten by retatrutide and mazdutide on weight. It has no dedicated obesity trial and no obesity indication.", "human_evidence": "REWIND: 9,901 adults aged 50 and older with type 2 diabetes and prior cardiovascular disease or risk factors, dulaglutide 1.5 mg weekly versus placebo, median follow up 5.4 years; the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death occurred less often with dulaglutide (hazard ratio 0.88, 95% CI 0.79 to 0.99). AWARD-11: 1,842 adults with type 2 diabetes on metformin randomized to 1.5, 3.0, or 4.5 mg weekly for 52 weeks; escalation to 3.0 and 4.5 mg gave dose related additional HbA1c and weight reductions. Phase 2 comparator data: retatrutide and mazdutide each produced greater weight loss than dulaglutide 1.5 mg in their diabetes trials.", "animal_evidence": "Preclinical studies established GLP-1 receptor pharmacology and the Fc fusion half life. Rodent studies showed thyroid C cell tumors, the basis of the boxed warning shared across long acting GLP-1 agonists; this has not been reproduced in humans.", "conditions": [ "type-2-diabetes" ], "literature_dosing": "Trulicity label: 0.75 mg subcutaneously once weekly, increased to 1.5 mg for additional glycemic control, then to 3.0 mg and 4.5 mg after at least 4 weeks on each dose (AWARD-11 regimen). REWIND used 1.5 mg weekly. Pediatric label (age 10 and older): 0.75 mg weekly, may increase to 1.5 mg.", "routes": [ "Subcutaneous injection once weekly (single dose pen)" ], "side_effects": [ "Nausea (dose dependent, attenuates with continued dosing)", "Diarrhea", "Vomiting", "Abdominal pain", "Decreased appetite", "Hypoglycemia when combined with insulin or sulfonylureas", "Gallbladder disease", "Pancreatitis (rare)", "Boxed warning for thyroid C cell tumors based on rodent data", "In REWIND, gastrointestinal events were the most common reason for discontinuation" ], "interactions": [ "Insulin and sulfonylureas: increased hypoglycemia risk, dose reduction usually needed", "Oral medications: delayed gastric emptying may alter absorption; label advises caution with narrow therapeutic window drugs", "Other GLP-1 or GIP/GLP-1 agonists: not studied in combination and not recommended" ], "contraindications": [ "Personal or family history of medullary thyroid carcinoma", "Multiple endocrine neoplasia syndrome type 2", "Prior serious hypersensitivity to dulaglutide", "Not for type 1 diabetes or diabetic ketoacidosis" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved product (Trulicity, September 2014; 3.0 mg and 4.5 mg doses added in 2020; pediatric indication in 2022; cardiovascular risk reduction indication based on REWIND). Because dulaglutide is a component of an approved drug, 503A pharmacies may compound it only for a documented patient specific need and may not produce essentially a copy of the commercial product. Dulaglutide is not available in a bulk powder form suitable for compounding. FDA listed dulaglutide injection as in shortage in its October 2024 to February 2025 GLP-1 updates, with all presentations available; it is not listed in FDA's shortage database as of September 27, 2026.", "typical_cost": "Trulicity list price is 1,006.93 USD per month for four pens at any strength; the manufacturer's self-pay pharmacy sells it from 389 USD per month. With commercial insurance and a manufacturer savings card a covered prescription is often 25 USD per month. Medicare Part D covers it for type 2 diabetes. No generic is available as of the last verified date.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail pharmacy as Trulicity.", "Not available as a compounded product; dulaglutide is not on any FDA bulks list. FDA listed dulaglutide injection as in shortage, with all presentations available, in its October 2024 to February 2025 GLP-1 updates; it is not listed in FDA's shortage database as of September 27, 2026.", "Products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "Is dulaglutide (Trulicity) FDA approved, and what for?", "a": "Yes. Dulaglutide (Trulicity) has been FDA approved since September 2014 to improve blood sugar in adults with type 2 diabetes, extended to children 10 and older in 2022, and it carries an indication to reduce major adverse cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes and cardiovascular disease or risk factors. It is not approved for weight loss. It is prescription only.", "source_ids": [ "fda-trulicity-label", "rewind" ] }, { "q": "Does Trulicity (dulaglutide) cause weight loss?", "a": "Modestly. In AWARD-11, 52 weeks of dulaglutide produced dose related weight loss in people with type 2 diabetes, with the 4.5 mg dose losing more than the 1.5 mg dose, in the range of roughly 3 to 5 kg. That is well below semaglutide 2.4 mg or tirzepatide, and in phase 2 diabetes trials dulaglutide 1.5 mg was outperformed on weight by both retatrutide and mazdutide. Trulicity has no weight management indication and no dedicated obesity trial.", "source_ids": [ "award-11", "retatrutide-t2d-phase2", "mazdutide-t2d-phase2" ] }, { "q": "What are the side effects of Trulicity?", "a": "Gastrointestinal effects dominate: nausea, diarrhea, vomiting, abdominal pain, and reduced appetite, which are dose dependent and fade with continued use; a 4 week pause at each dose step limits them. Serious risks include hypoglycemia with insulin or sulfonylureas, gallbladder disease, and pancreatitis. The label carries a boxed warning for thyroid C cell tumors seen in rodents. In REWIND, gastrointestinal events were the main reason for stopping.", "source_ids": [ "fda-trulicity-label", "rewind", "award-11" ] }, { "q": "What is the Trulicity dose on the FDA label?", "a": "Trulicity is a once weekly injection under the skin of the abdomen, thigh, or upper arm, at any time of day with or without food. Adults start at 0.75 mg weekly, may increase to 1.5 mg after 4 weeks, and can then increase in 1.5 mg steps (3 mg, then 4.5 mg) after at least 4 weeks on each dose; 4.5 mg is the maximum. Children 10 and older start at 0.75 mg and may go to a 1.5 mg maximum. A missed dose is taken only if at least 3 days remain before the next scheduled dose. The prescriber sets the dose.", "source_ids": [ "fda-trulicity-label" ] }, { "q": "How much does Trulicity cost?", "a": "Trulicity lists at 1,006.93 USD per month regardless of strength, and the manufacturer's self-pay pharmacy sells it from 389 USD per month. Most insured patients pay far less: commercial plans with the manufacturer savings card often bring it to 25 USD per month, and Medicare Part D covers it for type 2 diabetes. There is no generic as of the last verified date. Prices change often.", "source_ids": [ "fda-trulicity-label", "lilly-pricing-trulicity", "lillydirect-trulicity" ] }, { "q": "Is Trulicity (dulaglutide) banned by WADA?", "a": "No. GLP-1 receptor agonists including dulaglutide are not on the 2026 WADA Prohibited List or the 2027 list published in September 2026. Athletes with diabetes should still confirm documentation requirements with their anti-doping organization.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "Trulicity vs Ozempic: which is better?", "a": "For weight and HbA1c, semaglutide generally wins at its higher doses, and semaglutide has approvals for both diabetes and obesity while dulaglutide is diabetes only. Dulaglutide's advantages are the longest cardiovascular follow up (5.4 years in REWIND, hazard ratio 0.88), a pediatric indication, and a simple single use pen. Cost and insurance coverage usually decide between them for diabetes.", "source_ids": [ "rewind", "award-11", "fda-trulicity-label" ] }, { "q": "Does Trulicity protect the heart?", "a": "Yes. REWIND followed 9,901 adults with type 2 diabetes for a median of 5.4 years and found a 12% relative reduction in the composite of nonfatal heart attack, nonfatal stroke, or cardiovascular death (hazard ratio 0.88, 95% CI 0.79 to 0.99). Notably, most participants did not have prior cardiovascular disease, so the benefit extends to a primary prevention population.", "source_ids": [ "rewind" ] } ], "studies": [ { "pmid": "31189511", "title": "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND)", "year": 2019, "design": "Randomized, double blind, placebo controlled cardiovascular outcomes trial, median 5.4 years", "n": 9901, "population": "Adults 50 and older with type 2 diabetes and prior cardiovascular disease or cardiovascular risk factors", "outcome": "Major adverse cardiovascular events hazard ratio 0.88 (95% CI 0.79 to 0.99) with dulaglutide 1.5 mg weekly", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31189511/" }, { "pmid": "33397768", "title": "Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11)", "year": 2021, "design": "Randomized, double blind, dose comparison trial, 52 weeks", "n": 1842, "population": "Adults with type 2 diabetes inadequately controlled on metformin", "outcome": "Escalation to 3.0 mg and 4.5 mg gave dose related additional reductions in HbA1c and body weight versus 1.5 mg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33397768/" }, { "pmid": "37385280", "title": "Retatrutide for people with type 2 diabetes: a phase 2 trial (dulaglutide 1.5 mg active comparator)", "year": 2023, "design": "Randomized, double blind, placebo and active controlled phase 2 trial, 36 weeks", "n": 281, "population": "Adults with type 2 diabetes", "outcome": "Dulaglutide 1.5 mg produced smaller weight and HbA1c reductions than higher dose retatrutide", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/" } ], "sources": [ { "id": "rewind", "type": "pubmed", "title": "Gerstein HC et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31189511/", "pmid": "31189511", "year": 2019 }, { "id": "award-11", "type": "pubmed", "title": "Frias JP et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11). Diabetes Care 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33397768/", "pmid": "33397768", "year": 2021 }, { "id": "retatrutide-t2d-phase2", "type": "pubmed", "title": "Rosenstock J et al. Retatrutide for people with type 2 diabetes: a phase 2 trial. Lancet 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/", "pmid": "37385280", "year": 2023 }, { "id": "mazdutide-t2d-phase2", "type": "pubmed", "title": "Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a phase 2 trial (dulaglutide comparator). Diabetes Care 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/", "pmid": "37943529", "year": 2024 }, { "id": "fda-trulicity-label", "type": "fda", "title": "FDA prescribing information for Trulicity (dulaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=trulicity", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 }, { "id": "lilly-pricing-trulicity", "type": "other", "title": "Manufacturer pricing page: dulaglutide list price and savings options, accessed 2026-09-27", "url": "https://pricinginfo.lilly.com/trulicity" }, { "id": "lillydirect-trulicity", "type": "other", "title": "Manufacturer direct pharmacy: Trulicity self-pay price, accessed 2026-09-27", "url": "https://www.lilly.com/lillydirect/medicines/trulicity" }, { "id": "fda-glp1-shortage-updates", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (GLP-1 shortage status updates, including liraglutide, and the April 1, 2026 policy update on essentially copies)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize", "year": 2026 }, { "id": "fda-drug-shortages-dulaglutide", "type": "fda", "title": "FDA Drug Shortages database (dulaglutide not listed as of September 27, 2026)", "url": "https://dps.fda.gov/drugshortages", "year": 2026 } ], "related": [ "semaglutide", "liraglutide", "exenatide", "tirzepatide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Dulaglutide (Trulicity): evidence and access", "description": "Trulicity is dulaglutide, a weekly GLP-1 for type 2 diabetes. Heart outcome data, weight effects, side effects, FDA label doses, cost, and legal status.", "h1": "Dulaglutide (Trulicity)", "headings": { "safety": "Trulicity side effects in trials" } } }, { "slug": "exenatide", "name": "Exenatide", "aliases": [ "Byetta", "Bydureon", "Bydureon BCise", "exendin-4", "synthetic exendin-4", "AC2993" ], "class": "GLP-1 receptor agonist (synthetic 39 amino acid exendin-4, originally isolated from Gila monster saliva; twice daily and once weekly extended release forms)", "one_liner": "The first GLP-1 drug, FDA approved in 2005; lowers HbA1c (3 month blood sugar) 0.8 to 1.9 points with 2 to 4 kg weight loss; no proven heart benefit.", "summary": "Exenatide is a synthetic version of exendin-4, a peptide from Gila monster saliva that activates the GLP-1 receptor, the target of a gut hormone that boosts insulin after meals. It was the first drug in the class, FDA approved as twice daily Byetta in 2005 and as once weekly extended release Bydureon in 2012, for type 2 diabetes only. It lowers HbA1c (a measure of average blood sugar over about 3 months) by about 0.8 to 1.9 percentage points with 2 to 4 kg of weight loss, and in the 14,752 person EXSCEL trial it was safe but did not significantly reduce cardiovascular events (heart attacks, strokes, and cardiovascular deaths), so it has largely been superseded by liraglutide, dulaglutide, and semaglutide.", "mechanism": "Exenatide shares about 53% sequence identity with human GLP-1 but resists breakdown by the DPP-4 enzyme, giving a half life of about 2.4 hours for the immediate release form. It activates the GLP-1 receptor to increase glucose dependent insulin secretion, suppress inappropriately high glucagon, slow gastric emptying, and reduce food intake. The extended release form embeds exenatide in biodegradable microspheres that release it over about 10 weeks after each weekly injection.", "evidence_grade": "human_rct", "evidence_summary": "Multiple randomized controlled trials in type 2 diabetes since 2004, plus a 14,752 person cardiovascular outcomes trial. Twice daily exenatide lowered HbA1c by 0.8 points versus a 0.1 point rise on placebo over 30 weeks in metformin treated patients (n = 336). Once weekly exenatide lowered HbA1c by 1.9 points over 30 weeks (DURATION-1, n = 295) but was less effective than liraglutide 1.8 mg (DURATION-6, n = 912). EXSCEL showed a hazard ratio of 0.91 for major adverse cardiovascular events (95% CI 0.83 to 1.00), noninferior but not superior to placebo.", "human_evidence": "DeFronzo 2005: 336 adults with type 2 diabetes on metformin, 30 weeks; HbA1c change minus 0.78 points (10 ug twice daily), minus 0.40 (5 ug) versus plus 0.08 on placebo; weight change minus 2.8 kg and minus 1.6 kg. DURATION-1: 295 adults, 30 weeks; exenatide 2 mg weekly lowered HbA1c 1.9 points versus 1.5 for 10 ug twice daily, with 77% versus 61% reaching HbA1c 7% or less; weight loss over 4 kg at 52 weeks in the extension. DURATION-6: 912 adults, 26 weeks; liraglutide 1.8 mg daily lowered HbA1c 1.48 points versus 1.28 for weekly exenatide, so exenatide failed noninferiority. EXSCEL: 14,752 adults with type 2 diabetes (73% with prior cardiovascular disease), median 3.2 years; primary outcome 11.4% versus 12.2% (hazard ratio 0.91, P = 0.06 for superiority).", "animal_evidence": "Exendin-4 was characterized in Gila monster venom and shown to be a potent GLP-1 receptor agonist in rodent models of glucose control. Rodent studies of the extended release form showed thyroid C cell tumors, the basis of the boxed warning on Bydureon; the twice daily form does not carry that warning.", "conditions": [ "type-2-diabetes" ], "literature_dosing": "Byetta label and DeFronzo 2005: 5 ug subcutaneously twice daily within 60 minutes before morning and evening meals for 4 weeks, then 10 ug twice daily. Bydureon BCise label and DURATION-1: 2 mg subcutaneously once weekly. Both regimens are for type 2 diabetes in adults; Bydureon BCise is also labeled for children 10 and older.", "routes": [ "Subcutaneous injection twice daily before meals (immediate release pen)", "Subcutaneous injection once weekly (extended release microsphere autoinjector)" ], "side_effects": [ "Nausea (most common, mild to moderate, decreases over time)", "Vomiting and diarrhea", "Injection site nodules with the extended release form (microsphere deposits)", "Hypoglycemia when combined with sulfonylureas or insulin", "Pancreatitis (rare; not increased in EXSCEL)", "Acute kidney injury reported post marketing, usually with dehydration from vomiting", "Boxed warning for thyroid C cell tumors on the extended release form only", "Anti-exenatide antibodies in a substantial minority, occasionally reducing efficacy" ], "interactions": [ "Sulfonylureas and insulin: increased hypoglycemia risk, dose reduction usually needed", "Oral medications that depend on threshold concentrations (for example antibiotics and oral contraceptives): label advises taking them at least 1 hour before exenatide because of delayed gastric emptying", "Warfarin: post marketing reports of increased INR with bleeding; monitor", "Other GLP-1 or GIP/GLP-1 agonists: not recommended in combination" ], "contraindications": [ "Extended release form: personal or family history of medullary thyroid carcinoma or MEN2", "Prior serious hypersensitivity to exenatide", "History of drug induced immune mediated thrombocytopenia from exenatide", "Severe renal impairment or end stage renal disease (not recommended)", "Not for type 1 diabetes or diabetic ketoacidosis" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved products (Byetta April 2005, Bydureon January 2012, Bydureon BCise October 2017) for type 2 diabetes. Because exenatide is a component of approved drugs, 503A pharmacies may compound it only for a documented patient specific need and may not produce essentially a copy of a marketed product. Exenatide was not part of the semaglutide and tirzepatide shortage era. Product presentations have narrowed over time; check DailyMed for what is currently marketed.", "typical_cost": "Byetta and Bydureon BCise list at roughly 800 to 1,000 USD per month. With commercial insurance a covered prescription is often 25 to 100 USD per month, and Medicare Part D covers exenatide for type 2 diabetes. No generic is available as of the last verified date, and many formularies now prefer newer GLP-1 agonists.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail or specialty pharmacy as Byetta or Bydureon BCise.", "Not available through compounding pharmacies or telehealth peptide clinics as a compounded product.", "Products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "Is exenatide FDA approved and what is it for?", "a": "Yes. Exenatide was the first GLP-1 receptor agonist (a drug that mimics the gut hormone GLP-1) approved by FDA, as twice daily Byetta in April 2005, followed by once weekly Bydureon in 2012 and Bydureon BCise in 2017. It is approved only to improve blood sugar in type 2 diabetes (Bydureon BCise also in children 10 and older). It is not approved for weight loss and has no obesity trial.", "source_ids": [ "fda-byetta-label", "fda-bydureon-label" ] }, { "q": "Does exenatide work for weight loss?", "a": "Only modestly, and it is not approved for it. In the 30 week trial of twice daily exenatide with metformin, weight fell 2.8 kg at 10 ug and 1.6 kg at 5 ug versus placebo. In DURATION-1 the weekly form produced more than 4 kg of loss at 52 weeks. These effects are far below semaglutide 2.4 mg or tirzepatide, which is why exenatide is rarely chosen when weight is the goal.", "source_ids": [ "defronzo-2005", "duration-1-52wk" ] }, { "q": "What are the side effects of exenatide?", "a": "Nausea is the most common, affecting a large share of patients early and easing over weeks; vomiting and diarrhea also occur. The weekly form causes injection site nodules from its microspheres. Hypoglycemia is a risk with sulfonylureas or insulin. Rare reports include pancreatitis and acute kidney injury after dehydration from vomiting. Only the extended release form carries the boxed thyroid C cell warning. In EXSCEL, pancreatitis, pancreatic cancer, and medullary thyroid carcinoma rates did not differ from placebo.", "source_ids": [ "exscel", "fda-bydureon-label", "defronzo-2005" ] }, { "q": "How is exenatide taken and what is the dose?", "a": "Byetta is injected under the skin twice daily within an hour before the morning and evening meals, starting at 5 ug and increasing to 10 ug after 4 weeks. Bydureon BCise is injected once weekly at 2 mg, at any time of day, using an autoinjector that must be shaken and used immediately. Neither should be injected after a meal.", "source_ids": [ "fda-byetta-label", "fda-bydureon-label", "duration-1" ] }, { "q": "How much does exenatide cost?", "a": "Byetta and Bydureon BCise list at roughly 800 to 1,000 USD per month. Insured patients usually pay far less, often 25 to 100 USD with commercial coverage, and Medicare Part D covers it for type 2 diabetes. No generic exists as of the last verified date. Many insurers now steer patients to newer weekly GLP-1 agonists instead. Prices change often.", "source_ids": [ "fda-byetta-label" ] }, { "q": "Is exenatide banned by WADA?", "a": "No. GLP-1 receptor agonists including exenatide are not on the 2026 WADA Prohibited List or the 2027 list published in September 2026. Athletes should confirm any documentation requirements with their anti-doping organization.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "Exenatide vs liraglutide: which is better?", "a": "Liraglutide. In the DURATION-6 head to head trial of 912 adults, liraglutide 1.8 mg daily lowered HbA1c by 1.48 points versus 1.28 for weekly exenatide, and weekly exenatide failed its noninferiority test. Liraglutide also reduced cardiovascular events in LEADER, while exenatide did not reach significance in EXSCEL (hazard ratio 0.91). Exenatide's weekly form does have less nausea than daily liraglutide.", "source_ids": [ "duration-6", "exscel" ] }, { "q": "Does exenatide protect the heart?", "a": "It is safe but the benefit was not proven. EXSCEL followed 14,752 people with type 2 diabetes for a median 3.2 years; major adverse cardiovascular events occurred in 11.4% on weekly exenatide versus 12.2% on placebo (hazard ratio 0.91, 95% CI 0.83 to 1.00). That met noninferiority but missed superiority (P = 0.06), so unlike liraglutide, dulaglutide, and semaglutide, exenatide carries no cardiovascular risk reduction indication.", "source_ids": [ "exscel" ] } ], "studies": [ { "pmid": "15855572", "title": "Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes", "year": 2005, "design": "Randomized, triple blind, placebo controlled trial, 30 weeks", "n": 336, "population": "Adults with type 2 diabetes inadequately controlled on maximal metformin", "outcome": "HbA1c change minus 0.78 points (10 ug twice daily) and minus 0.40 (5 ug) versus plus 0.08 placebo; weight minus 2.8 kg and minus 1.6 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/15855572/" }, { "pmid": "18782641", "title": "Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study (DURATION-1)", "year": 2008, "design": "Randomized, open label, noninferiority trial, 30 weeks", "n": 295, "population": "Adults with type 2 diabetes, drug naive or on oral agents", "outcome": "HbA1c change minus 1.9 points with 2 mg weekly versus minus 1.5 with 10 ug twice daily; 77% versus 61% reached HbA1c 7% or less", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18782641/" }, { "pmid": "20215461", "title": "DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks", "year": 2010, "design": "Open label extension of a randomized trial, 52 weeks total", "n": 258, "population": "Adults with type 2 diabetes continuing or switching to weekly exenatide", "outcome": "HbA1c reduction of 2.0 points maintained at 52 weeks; body weight reduced by more than 4 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/20215461/" }, { "pmid": "23141817", "title": "Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6)", "year": 2013, "design": "Randomized, open label, parallel group trial, 26 weeks", "n": 912, "population": "Adults with type 2 diabetes on lifestyle and oral agents", "outcome": "HbA1c change minus 1.48 points with liraglutide 1.8 mg versus minus 1.28 with weekly exenatide; exenatide did not meet noninferiority", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23141817/" }, { "pmid": "28910237", "title": "Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes (EXSCEL)", "year": 2017, "design": "Randomized, double blind, placebo controlled cardiovascular outcomes trial, median 3.2 years", "n": 14752, "population": "Adults with type 2 diabetes with or without prior cardiovascular disease", "outcome": "Major adverse cardiovascular events 11.4% versus 12.2% (hazard ratio 0.91, 95% CI 0.83 to 1.00); noninferior, not superior", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/28910237/" } ], "sources": [ { "id": "defronzo-2005", "type": "pubmed", "title": "DeFronzo RA et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15855572/", "pmid": "15855572", "year": 2005 }, { "id": "duration-1", "type": "pubmed", "title": "Drucker DJ et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes (DURATION-1). Lancet 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18782641/", "pmid": "18782641", "year": 2008 }, { "id": "duration-1-52wk", "type": "pubmed", "title": "Buse JB et al. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care 2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20215461/", "pmid": "20215461", "year": 2010 }, { "id": "duration-6", "type": "pubmed", "title": "Buse JB et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6). Lancet 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23141817/", "pmid": "23141817", "year": 2013 }, { "id": "exscel", "type": "pubmed", "title": "Holman RR et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017 (EXSCEL)", "url": "https://pubmed.ncbi.nlm.nih.gov/28910237/", "pmid": "28910237", "year": 2017 }, { "id": "fda-byetta-label", "type": "fda", "title": "FDA prescribing information for Byetta (exenatide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=byetta", "year": 2025 }, { "id": "fda-bydureon-label", "type": "fda", "title": "FDA prescribing information for Bydureon BCise (exenatide extended-release) injectable suspension, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=bydureon", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 } ], "related": [ "liraglutide", "dulaglutide", "semaglutide", "pramlintide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 2 }, { "slug": "survodutide", "name": "Survodutide", "aliases": [ "BI 456906", "glucagon/GLP-1 dual agonist", "survodutide (BI 456906)" ], "class": "Investigational dual agonist of the glucagon and GLP-1 receptors (acylated peptide, once weekly)", "one_liner": "Investigational glucagon/GLP-1 dual agonist: 13% weight loss at 76 weeks in phase 3 and strong liver (MASH) data, but not FDA approved.", "summary": "Survodutide is an investigational once weekly peptide that activates both the glucagon and GLP-1 receptors, developed for obesity and metabolic dysfunction associated steatohepatitis (MASH). In the 76 week phase 3 SYNCHRONIZE-1 trial (n = 725) it produced 12.2% to 13.0% weight loss versus 5.4% on placebo, and in a 48 week phase 2 MASH trial (n = 293) up to 62% of participants had histologic MASH improvement versus 14% on placebo. As of September 2026 it is not FDA approved, cannot lawfully be compounded, and is prohibited in sport under WADA section S0.", "mechanism": "Survodutide is a glucagon analog engineered to also activate the GLP-1 receptor. GLP-1 receptor activation reduces appetite, slows gastric emptying, and increases glucose dependent insulin release. Glucagon receptor activation increases energy expenditure and hepatic fat oxidation, which is the rationale for its liver disease program, but also raises glucose output, which the GLP-1 component is designed to offset. It is acylated for once weekly dosing.", "evidence_grade": "human_rct", "evidence_summary": "One published phase 3 obesity trial (SYNCHRONIZE-1, n = 725, 76 weeks), one phase 3 trial in obesity with MASLD (n = 216), a phase 2 MASH trial (n = 293, 48 weeks), and phase 1 and 2 dose finding studies. Weight loss in phase 3 was 12.2% (3.6 mg) and 13.0% (6.0 mg) versus 5.4% on placebo, a smaller placebo adjusted effect than tirzepatide or retatrutide in their trials. Those are treatment regimen estimand figures; under the efficacy estimand, which assumes participants stayed on treatment, the manufacturer reported up to 16.6% versus 3.2% on placebo. Histologic MASH improvement without worsening fibrosis occurred in 43% to 62% versus 14% on placebo in phase 2. A cardiovascular outcomes trial (SYNCHRONIZE-CVOT) is ongoing.", "human_evidence": "SYNCHRONIZE-1 (2026): 725 adults with BMI 30 or higher (or 27 with a complication) without diabetes, once weekly survodutide up to 3.6 mg or 6.0 mg or placebo for 76 weeks; mean weight change minus 12.2% (3.6 mg), minus 13.0% (6.0 mg), minus 5.4% (placebo) by treatment regimen estimand; 72.6%, 71.9%, and 46.3% lost at least 5%. Phase 2 MASH (2024): 293 adults with biopsy confirmed MASH and F1 to F3 fibrosis, 48 weeks; improvement in MASH without worsening fibrosis in 47% (2.4 mg), 62% (4.8 mg), and 43% (6.0 mg) versus 14% placebo; liver fat reduction of at least 30% in 63% to 67% of treated participants. SYNCHRONIZE-MASLD (2026): 216 adults with obesity and MASLD, phase 3, placebo controlled. Phase 1 (2023): 36 Japanese men with overweight or obesity, 16 weeks; placebo corrected weight change up to minus 12.4% at 4.8 mg weekly, with 37% withdrawing from escalation because of adverse events.", "animal_evidence": "Preclinical rodent studies established the dual receptor pharmacology, the additive weight effect of glucagon receptor agonism, and reductions in liver fat. Thyroid C cell findings are expected to be evaluated as with other GLP-1 based agonists; no label exists because the drug is not approved.", "conditions": [ "obesity" ], "literature_dosing": "SYNCHRONIZE-1: once weekly subcutaneous injection escalated over a prolonged period to a maintenance dose of 3.6 mg or 6.0 mg with dose flexibility permitted. Phase 2 MASH: 2.4, 4.8, or 6.0 mg weekly after a 24 week rapid escalation. No approved label exists; these are trial regimens only.", "routes": [ "Subcutaneous injection once weekly (clinical trials only)" ], "side_effects": [ "Gastrointestinal symptoms in 80.9% (3.6 mg) and 89.7% (6.0 mg) versus 47.9% placebo in SYNCHRONIZE-1, mostly mild to moderate", "Nausea, vomiting, diarrhea, and constipation", "Decreased appetite, which drove most withdrawals during dose escalation in phase 1", "Increased heart rate (glucagon receptor class effect)", "Transient delayed gastric emptying", "Long term safety and cardiovascular outcomes not yet reported" ], "interactions": [ "No approved label, so no formal interaction studies are published", "Delayed gastric emptying shown to reduce paracetamol absorption in phase 1; other oral drugs may be affected", "Hypoglycemia risk when combined with insulin or sulfonylureas is a class precaution", "Should not be combined with other GLP-1 based agonists (not studied)" ], "contraindications": [ "Not approved for any use; only available inside registered clinical trials", "Personal or family history of medullary thyroid carcinoma or MEN2 (class precaution, trial exclusion)", "Pregnancy and breastfeeding (excluded from trials)", "Competitive athletes subject to WADA testing (prohibited under S0)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved and not approved by any other regulator as of the last verification date. Because survodutide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded by 503A pharmacies or 503B outsourcing facilities. Any product sold as survodutide outside a clinical trial is an unapproved drug that has not been evaluated for identity, purity, or dose.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B while investigational.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is survodutide FDA approved or legal to buy?", "a": "No. Survodutide is investigational and has no approval from FDA or any other regulator as of September 2026. It cannot be compounded because it is not a component of an approved drug and is not on any FDA bulks list, so the only lawful access is a registered clinical trial. Products sold online as survodutide are unapproved drugs with no verification of what is in the vial.", "source_ids": [ "fda-glp1-compounding", "fda-503a-bulks", "synchronize-design" ] }, { "q": "How much weight do people lose on survodutide?", "a": "In the phase 3 SYNCHRONIZE-1 trial of 725 adults with obesity, mean weight loss at 76 weeks was 12.2% at 3.6 mg and 13.0% at 6.0 mg versus 5.4% on placebo, with about 72% of treated participants losing at least 5%. The placebo adjusted effect (about 7 to 8 percentage points) is smaller than semaglutide, tirzepatide, or retatrutide achieved in their trials, although the estimand and trial designs differ. A phase 1 study had shown placebo corrected losses up to 12.4% after only 16 weeks at 4.8 mg.", "source_ids": [ "synchronize-1", "survodutide-phase1" ] }, { "q": "What are the side effects of survodutide?", "a": "Gastrointestinal effects are very common: in SYNCHRONIZE-1 they affected 81% of the 3.6 mg group and 90% of the 6.0 mg group versus 48% on placebo, mostly mild to moderate. Nausea, vomiting, diarrhea, constipation, and loss of appetite lead the list, and in the phase 1 study 37% of participants stopped escalating because of adverse events, mainly decreased appetite. Heart rate rises as with other glucagon receptor agonists. No deaths were reported in phase 3. Long term safety is not established.", "source_ids": [ "synchronize-1", "survodutide-phase1" ] }, { "q": "How is survodutide taken?", "a": "In trials it is a once weekly subcutaneous injection. SYNCHRONIZE-1 escalated slowly to 3.6 mg or 6.0 mg weekly with dose flexibility, and the phase 2 MASH trial used 2.4, 4.8, or 6.0 mg weekly after a 24 week escalation. No approved dosing exists outside these protocols.", "source_ids": [ "synchronize-1", "survodutide-mash-phase2" ] }, { "q": "How much does survodutide cost?", "a": "It has no price because it is not on the market; trial participants receive it free. A list price will exist only if FDA approves it. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-glp1-compounding" ] }, { "q": "Is survodutide banned by WADA?", "a": "Yes. Survodutide has no approval from any government health authority, so it is prohibited at all times under section S0 (non-approved substances) of the WADA Prohibited List. Approved GLP-1 agonists are not prohibited, but that does not extend to investigational molecules.", "source_ids": [ "wada-list" ] }, { "q": "Survodutide vs tirzepatide: what is the difference?", "a": "Tirzepatide activates GIP and GLP-1 receptors and is FDA approved; survodutide activates glucagon and GLP-1 receptors and is investigational. On weight, tirzepatide 15 mg produced 20.9% loss at 72 weeks in SURMOUNT-1 versus survodutide's 13.0% at 76 weeks in SYNCHRONIZE-1, so tirzepatide is the more powerful weight drug. Survodutide's distinguishing data are in the liver: phase 2 MASH improvement in up to 62% of participants versus 14% on placebo, with fibrosis endpoints under study in phase 3.", "source_ids": [ "synchronize-1", "survodutide-mash-phase2" ] }, { "q": "Does survodutide help fatty liver disease (MASH)?", "a": "The phase 2 data are strong. In a 48 week trial of 293 adults with biopsy confirmed MASH and F1 to F3 fibrosis, MASH improved without worsening of fibrosis in 47%, 62%, and 43% of the 2.4, 4.8, and 6.0 mg groups versus 14% on placebo, and 63% to 67% had at least a 30% drop in liver fat. Phase 3 trials in MASH and in obesity with MASLD (216 participants) are the confirmatory step. No approval exists yet.", "source_ids": [ "survodutide-mash-phase2", "synchronize-masld" ] } ], "studies": [ { "pmid": "42253238", "title": "Survodutide once weekly for the treatment of adults with obesity (SYNCHRONIZE-1)", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 3 trial, 76 weeks", "n": 725, "population": "Adults with BMI 30 or higher, or 27 or higher with a complication, without diabetes", "outcome": "Mean weight change minus 12.2% (3.6 mg), minus 13.0% (6.0 mg), minus 5.4% (placebo); at least 5% loss in 72.6%, 71.9%, and 46.3%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/" }, { "pmid": "38847460", "title": "A phase 2 randomized trial of survodutide in MASH and fibrosis", "year": 2024, "design": "Randomized, double blind, placebo controlled phase 2 trial, 48 weeks", "n": 293, "population": "Adults with biopsy confirmed MASH and fibrosis stage F1 to F3", "outcome": "MASH improvement without worsening fibrosis in 47% (2.4 mg), 62% (4.8 mg), 43% (6.0 mg) versus 14% placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/38847460/" }, { "pmid": "42252333", "title": "Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD phase 3 trial", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 3 trial", "n": 216, "population": "Adults with obesity and MASLD", "outcome": "Phase 3 evaluation of weight and liver endpoints in obesity with MASLD", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42252333/" }, { "pmid": "36974349", "title": "A randomized phase 1 study of BI 456906, a dual glucagon receptor/GLP-1 receptor agonist, in healthy Japanese men with overweight/obesity", "year": 2023, "design": "Randomized, placebo controlled multiple rising dose phase 1 study, 16 weeks", "n": 36, "population": "Japanese men with BMI 23 to 40", "outcome": "Placebo corrected weight change minus 5.6% (1.8 mg weekly), minus 12.4% (4.8 mg weekly), minus 9.6% (2.4 mg twice weekly); 37% withdrew from escalation for adverse events", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36974349/" } ], "sources": [ { "id": "synchronize-1", "type": "pubmed", "title": "le Roux CW et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med 2026 (SYNCHRONIZE-1)", "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/", "pmid": "42253238", "year": 2026 }, { "id": "survodutide-mash-phase2", "type": "pubmed", "title": "Sanyal AJ et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38847460/", "pmid": "38847460", "year": 2024 }, { "id": "synchronize-masld", "type": "pubmed", "title": "Kaplan LM et al. Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD phase 3 trial. Nat Med 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42252333/", "pmid": "42252333", "year": 2026 }, { "id": "survodutide-phase1", "type": "pubmed", "title": "A randomized phase 1 study of BI 456906 in healthy Japanese men with overweight/obesity. Diabetes Obes Metab 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36974349/", "pmid": "36974349", "year": 2023 }, { "id": "synchronize-design", "type": "pubmed", "title": "Wharton S et al. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE-1 and -2). Obesity 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39495965/", "pmid": "39495965", "year": 2025 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "synchronize-1-topline", "type": "other", "title": "Manufacturer press release: SYNCHRONIZE-1 topline results (April 28, 2026)", "url": "https://www.boehringer-ingelheim.com/us/human-health/metabolic-diseases/results-phase-iii-synchronize-1-obesity-trial", "year": 2026 } ], "related": [ "mazdutide", "retatrutide", "tirzepatide", "semaglutide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 2 }, { "slug": "mazdutide", "name": "Mazdutide", "aliases": [ "IBI362", "LY3305677", "GLP-1/glucagon dual agonist", "mazdutide (IBI362)" ], "class": "Dual agonist of the GLP-1 and glucagon receptors (oxyntomodulin analog, acylated, once weekly)", "one_liner": "GLP-1/glucagon dual agonist with 14% weight loss at 48 weeks in a Chinese phase 3 trial and 18% at 16 mg in a US phase 2; not FDA approved.", "summary": "Mazdutide is a once weekly oxyntomodulin analog that activates both the GLP-1 and glucagon receptors, developed primarily in China with a parallel US program. In the 48 week GLORY-1 phase 3 trial of 610 Chinese adults, the 6 mg dose produced 14.0% weight loss versus 0.3% on placebo, and in a 32 week US phase 2 trial (n = 179) the 16 mg dose produced 18.1% versus 0.9%. As of September 2026 it is not FDA approved and cannot lawfully be compounded or sold in the United States; China's drug regulator approved it for chronic weight management in adults in June 2025 and for glycemic control in adults with type 2 diabetes in September 2025, which has no bearing on US legality.", "mechanism": "Mazdutide is an analog of oxyntomodulin, a gut hormone that naturally activates both the GLP-1 and glucagon receptors. GLP-1 receptor activation reduces appetite, slows gastric emptying, and increases glucose dependent insulin secretion. Glucagon receptor activation raises energy expenditure and liver fat oxidation, which adds to weight loss and improves liver enzymes and lipids. A fatty acid side chain gives a once weekly half life.", "evidence_grade": "human_rct", "evidence_summary": "Multiple randomized controlled trials, mostly in China. GLORY-1 (n = 610, 48 weeks) showed 11.0% and 14.0% weight loss at 4 and 6 mg versus 0.3% placebo. A US phase 2 trial (n = 179, 32 weeks) showed 7.3%, 15.6%, and 18.1% at 3 to 6, 10, and 16 mg versus 0.9% placebo. Phase 2 and phase 3 type 2 diabetes trials showed HbA1c reductions of about 1.4 to 1.7 points and superiority to dulaglutide 1.5 mg on weight. A 2026 meta-analysis pooled 9 trials (n = 2,292). No cardiovascular outcomes trial has reported.", "human_evidence": "GLORY-1 (2025): 610 Chinese adults with BMI 28 or higher (or 24 with a comorbidity), mazdutide 4 mg, 6 mg, or placebo for 48 weeks; weight change at 32 weeks minus 10.1%, minus 12.6%, plus 0.5%, and at 48 weeks minus 11.0%, minus 14.0%, plus 0.3%; 49.5% of the 6 mg group lost at least 15% versus 2.0% on placebo. US phase 2 (2026): 179 adults without diabetes, 32 weeks; weight change minus 7.3% (3 to 6 mg), minus 15.6% (10 mg), minus 18.1% (16 mg) versus minus 0.9% placebo. Phase 2 type 2 diabetes (2024): 250 Chinese adults, 20 weeks; HbA1c change minus 1.41 to minus 1.67 points versus minus 1.35 with dulaglutide and plus 0.03 with placebo, weight up to minus 7.1%. Phase 3 type 2 diabetes trials versus placebo and versus dulaglutide were published in 2026.", "animal_evidence": "Preclinical rodent studies established the dual receptor pharmacology and additive weight and liver fat effects of glucagon receptor agonism. Thyroid C cell findings are a class expectation for long acting GLP-1 agonists; no FDA label exists.", "conditions": [ "obesity", "type-2-diabetes" ], "literature_dosing": "GLORY-1: once weekly subcutaneous injection escalated to a maintenance dose of 4 mg or 6 mg. US phase 2: escalated to 3 to 6, 10, or 16 mg weekly. Type 2 diabetes phase 2: 3, 4.5, or 6 mg weekly. No FDA approved label exists; these are trial regimens only.", "routes": [ "Subcutaneous injection once weekly" ], "side_effects": [ "Diarrhea (36% in the type 2 diabetes phase 2 trial)", "Decreased appetite (29%)", "Nausea (23%)", "Vomiting (14%)", "Hypoglycemia in people with diabetes (10% versus 8% placebo)", "Gastrointestinal events in general were mostly mild to moderate; discontinuation for adverse events was 1.5% or less in GLORY-1", "Increased heart rate (glucagon receptor class effect)", "Long term safety and cardiovascular outcomes not yet reported" ], "interactions": [ "No FDA label, so no formal US interaction studies are published", "Class precautions apply: hypoglycemia with insulin or sulfonylureas, and altered absorption of oral drugs from delayed gastric emptying", "Should not be combined with other GLP-1 based agonists (not studied)" ], "contraindications": [ "Not FDA approved; in the United States only available inside registered clinical trials", "Personal or family history of medullary thyroid carcinoma or MEN2 (class precaution, trial exclusion)", "Pregnancy and breastfeeding (excluded from trials)", "Competitive athletes should treat it as prohibited pending confirmation of its approval status with their anti-doping organization" ], "wada_status": "unclear", "fda_status": "not_eligible", "compounding_status": "Not FDA approved as of the last verification date. Because mazdutide is not a component of an FDA approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded or dispensed in the United States, and any product sold as mazdutide in the US is an unapproved drug. Its development and registration have centered on China, where the national drug regulator approved it for chronic weight management in adults (June 2025) and for type 2 diabetes (September 2025); those approvals do not make it legal to sell or compound in the US.", "typical_cost": "Not available through licensed channels in the United States. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product in the United States and not eligible for compounding under section 503A or 503B while investigational.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is mazdutide FDA approved or legal in the United States?", "a": "No. Mazdutide is not FDA approved as of September 2026, and because it is not a component of an approved drug and is not on any FDA bulks list it cannot be compounded. In the US the only lawful access is a registered clinical trial. It is approved in China for chronic weight management and type 2 diabetes, but a Chinese approval has no bearing on US legality.", "source_ids": [ "fda-glp1-compounding", "fda-503a-bulks", "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval", "mazdutide-first-approval" ] }, { "q": "How much weight do people lose on mazdutide?", "a": "In GLORY-1, a 48 week phase 3 trial of 610 Chinese adults, mean weight loss was 11.0% at 4 mg and 14.0% at 6 mg versus 0.3% on placebo, and about half of the 6 mg group lost at least 15%. In a 32 week US phase 2 trial of 179 adults, higher doses did more: 15.6% at 10 mg and 18.1% at 16 mg versus 0.9% on placebo. The higher US doses are being carried into phase 3.", "source_ids": [ "glory-1", "mazdutide-us-phase2" ] }, { "q": "What are the side effects of mazdutide?", "a": "Gastrointestinal effects dominate. In the phase 2 diabetes trial, diarrhea affected 36%, decreased appetite 29%, nausea 23%, and vomiting 14%, with hypoglycemia in 10% versus 8% on placebo. Events were mostly mild to moderate, and in GLORY-1 only 0.5% to 1.5% of treated participants stopped for adverse events. Heart rate rises as with other glucagon receptor agonists. Long term safety and cardiovascular outcomes have not been reported.", "source_ids": [ "mazdutide-t2d-phase2", "glory-1" ] }, { "q": "How is mazdutide taken?", "a": "In trials it is a once weekly subcutaneous injection escalated to a maintenance dose: 4 or 6 mg in GLORY-1, 3 to 6, 10, or 16 mg in the US phase 2 trial, and 3 to 6 mg in the diabetes trials. No FDA approved dosing exists.", "source_ids": [ "glory-1", "mazdutide-us-phase2", "mazdutide-t2d-phase2" ] }, { "q": "How much does mazdutide cost?", "a": "It has no US price because it is not on the US market; trial participants receive it free. Any pricing in other countries does not apply to US patients. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-glp1-compounding" ] }, { "q": "Is mazdutide banned by WADA?", "a": "Unclear, and athletes should treat it as prohibited. WADA section S0 bans any substance with no current approval by any government health authority for human therapeutic use. Mazdutide is not FDA approved, but China's drug regulator approved it in June 2025; whether that approval takes it outside S0 is a question for the athlete's anti-doping organization. Approved GLP-1 agonists like semaglutide are not prohibited.", "source_ids": [ "wada-list", "mazdutide-china-obesity-approval" ] }, { "q": "Mazdutide vs survodutide: what is the difference?", "a": "Both are glucagon/GLP-1 dual agonists and neither is FDA approved. Mazdutide is an oxyntomodulin analog developed mainly in China; survodutide is a glucagon analog developed for obesity and MASH. On weight, mazdutide reached 14.0% at 6 mg over 48 weeks in GLORY-1 and 18.1% at 16 mg over 32 weeks in the US, while survodutide reached 13.0% at 6.0 mg over 76 weeks in SYNCHRONIZE-1. The trials differ in populations and estimands, so this is not a head to head comparison.", "source_ids": [ "glory-1", "mazdutide-us-phase2", "synchronize-1" ] }, { "q": "Does mazdutide work for type 2 diabetes?", "a": "Yes in trials. In the 20 week phase 2 trial of 250 Chinese adults, HbA1c fell 1.41 to 1.67 points with mazdutide versus 1.35 with dulaglutide 1.5 mg and 0.03 with placebo, with up to 7.1% weight loss. Phase 3 trials versus placebo and versus dulaglutide were published in 2026, and a meta-analysis of 9 trials found mazdutide outperformed dulaglutide on both HbA1c and weight. It has no FDA diabetes indication.", "source_ids": [ "mazdutide-t2d-phase2", "mazdutide-meta-2026" ] } ], "studies": [ { "pmid": "40421736", "title": "Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1)", "year": 2025, "design": "Randomized, double blind, placebo controlled phase 3 trial, 48 weeks", "n": 610, "population": "Chinese adults with BMI 28 or higher, or 24 to 28 with a weight related condition", "outcome": "Weight change at 48 weeks minus 11.0% (4 mg), minus 14.0% (6 mg), plus 0.3% (placebo); at least 15% loss in 35.7%, 49.5%, and 2.0%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/40421736/" }, { "pmid": "42628555", "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based phase 2 randomised placebo-controlled trial", "year": 2026, "design": "Randomized, double blind, placebo controlled phase 2 trial, 32 weeks (48 week extension)", "n": 179, "population": "US adults without diabetes with BMI 30 or higher", "outcome": "Weight change minus 7.3% (3 to 6 mg), minus 15.6% (10 mg), minus 18.1% (16 mg) versus minus 0.9% placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42628555/" }, { "pmid": "37943529", "title": "Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial", "year": 2024, "design": "Randomized, double blind, placebo and open label dulaglutide controlled phase 2 trial, 20 weeks", "n": 250, "population": "Chinese adults with type 2 diabetes on diet and exercise or metformin", "outcome": "HbA1c change minus 1.41 to minus 1.67 points versus minus 1.35 dulaglutide and plus 0.03 placebo; weight up to minus 7.1%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/" }, { "pmid": "42410325", "title": "Efficacy and safety of mazdutide in predominantly Chinese adults with obesity and/or type 2 diabetes: a systematic review and meta-analysis", "year": 2026, "design": "Systematic review and meta-analysis of 9 randomized controlled trials", "n": 2292, "population": "Adults with overweight or obesity and/or type 2 diabetes, predominantly Chinese", "outcome": "Weight reduction versus placebo of 6.6% to 11.1% at 3 to 6 mg in obesity; superior to dulaglutide on weight and HbA1c in type 2 diabetes", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42410325/" } ], "sources": [ { "id": "glory-1", "type": "pubmed", "title": "Ji L et al. Once-weekly mazdutide in Chinese adults with obesity or overweight. N Engl J Med 2025 (GLORY-1)", "url": "https://pubmed.ncbi.nlm.nih.gov/40421736/", "pmid": "40421736", "year": 2025 }, { "id": "mazdutide-us-phase2", "type": "pubmed", "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based phase 2 trial. Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42628555/", "pmid": "42628555", "year": 2026 }, { "id": "mazdutide-t2d-phase2", "type": "pubmed", "title": "Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a phase 2 trial. Diabetes Care 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/", "pmid": "37943529", "year": 2024 }, { "id": "mazdutide-meta-2026", "type": "pubmed", "title": "Efficacy and safety of mazdutide in predominantly Chinese adults with obesity and/or type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42410325/", "pmid": "42410325", "year": 2026 }, { "id": "synchronize-1", "type": "pubmed", "title": "le Roux CW et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med 2026 (SYNCHRONIZE-1)", "url": "https://pubmed.ncbi.nlm.nih.gov/42253238/", "pmid": "42253238", "year": 2026 }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss", "year": 2025 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "mazdutide-first-approval", "type": "pubmed", "title": "Shirley M. Mazdutide: First Approval. Drugs 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41028652/", "pmid": "41028652", "year": 2025 }, { "id": "mazdutide-china-obesity-approval", "type": "other", "title": "Manufacturer press release: China's drug regulator (NMPA) approves mazdutide for chronic weight management (June 27, 2025)", "url": "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html", "year": 2025 }, { "id": "mazdutide-china-t2d-approval", "type": "other", "title": "Manufacturer press release: China's drug regulator (NMPA) approves mazdutide for glycemic control in type 2 diabetes (September 19, 2025)", "url": "https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-received-approval-from-chinas-nmpa-for-glycemic-control-in-adults-with-type-2-diabetes-302561434.html", "year": 2025 } ], "related": [ "survodutide", "retatrutide", "dulaglutide", "tirzepatide" ], "cluster": "glp1", "last_verified": "2026-09-27", "review_status": "draft", "version": 2 }, { "slug": "bpc-157", "name": "BPC-157", "aliases": [ "Body Protection Compound 157", "Pentadecapeptide BPC 157", "BPC 157", "BPC-157 arginate", "Bepecin", "PL 14736", "BPC157", "BPC-157 peptide" ], "class": "Synthetic gastric pentadecapeptide (15 amino acids), fragment of body protection compound", "one_liner": "A 15 amino acid peptide with strong animal healing data, no randomized human trial in PubMed, and a shifting FDA compounding status.", "summary": "BPC-157 is a lab-made chain of 15 amino acids (the building blocks of proteins) copied from part of a protein found in human gastric juice (stomach fluid). In rodents it consistently speeds tendon, ligament, muscle, and gut healing, but as of September 2026 there is no randomized human trial (one that assigns people to the drug or a placebo by chance) indexed in PubMed, so its evidence grade is animal-only. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and its advisory committee recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but a final listing has not been published.", "mechanism": "In animal and cell models BPC-157 upregulates growth factor receptors (including EGR-1 and its repressor NAB2), increases nitric oxide system activity, and promotes angiogenesis through VEGFR2 signaling. It also increases fibroblast migration and outgrowth from tendon explants. These mechanisms are documented in rodent and in vitro work and have not been confirmed in humans.", "evidence_grade": "animal_only", "evidence_summary": "Dozens of rodent studies from a small number of laboratories, mostly in Zagreb, report faster tendon, ligament, muscle, bone, and gastrointestinal healing, and a 2025 systematic review counted 35 preclinical studies and 1 clinical study in the musculoskeletal literature. Independent replication is limited. No randomized controlled trial in humans has been published as of the last verification date. The only indexed human data are three small uncontrolled pilot reports from one clinic (knee pain, interstitial cystitis, and intravenous safety), which have no comparison group; they are listed but do not raise the grade.", "human_evidence": "No randomized controlled trial identified. Three small uncontrolled pilot reports from a single clinic are indexed: a retrospective phone survey of 16 people given knee injections (12 BPC-157 alone, 4 combined with thymosin beta-4), in which 14 reported relief; a pilot in 12 women with interstitial cystitis given a single bladder wall injection, all of whom reported improvement; and a 2 person intravenous safety pilot that found no changes in heart, liver, kidney, thyroid, or glucose markers. None had a control group, blinding, or long follow-up. A 2025 narrative review described human data as extremely limited, and a 2025 systematic review found no clinical safety data.", "animal_evidence": "In rats, BPC-157 accelerated Achilles tendon healing and increased tendon fibroblast outgrowth, survival, and migration in explant models. Rodent studies also report faster healing of transected muscle, ligament, bone, and gastrointestinal lesions, and protection against NSAID induced gut injury, given by injection, orally in drinking water, or topically. In rats and endothelial cells it increased blood vessel growth and VEGFR2 expression. A pharmacokinetic study in rats and dogs found an elimination half-life under 30 minutes after intravenous or intramuscular injection, with rapid breakdown into amino acids.", "conditions": [ "tendon-injury", "muscle-recovery", "wound-healing", "inflammation" ], "literature_dosing": "Not established in human literature. Rodent studies gave BPC-157 by injection, in drinking water, or topically; animal doses do not translate to a human dose, and no human dose finding study has been published.", "routes": [ "Subcutaneous injection (as sold)", "Oral capsule (as sold)", "Intraperitoneal, oral in water, and topical (animal studies)" ], "side_effects": [ "No systematic human safety data; three small uncontrolled pilot reports (about 30 people in total) reported no adverse events", "Injection site reactions reported anecdotally", "Nausea and dizziness reported anecdotally", "Theoretical concern about promoting growth of existing tumors because it stimulates angiogenesis through VEGFR2 in animal and cell studies (not demonstrated in humans)", "Unverified identity, purity, and sterility of products sold as research chemicals" ], "interactions": [ "No formal human interaction studies exist", "Animal studies show BPC-157 modulates the nitric oxide system, so a theoretical interaction with nitrates, PDE5 inhibitors, and antihypertensives has been proposed but not tested" ], "contraindications": [ "Active cancer or history of cancer (theoretical angiogenesis concern)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "under_review", "compounding_status": "Removed from the FDA 503A Category 2 list (substances with significant safety risks) on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding BPC-157 to the 503A bulks list. As of the last verification date FDA has not published a final rule listing it, so state boards and pharmacies vary in whether they will compound it. It is not an FDA approved drug and is not eligible for 503B outsourcing.", "typical_cost": "No lawful compounded price: BPC-157 is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is BPC-157?", "a": "BPC-157 is a synthetic peptide of 15 amino acids copied from a fragment of a protein in human gastric juice (stomach fluid). It is studied for tendon, muscle, and gut healing, almost entirely in rats. It is not an FDA approved drug, it is prohibited in sport, and PeptideAgent grades its evidence animal-only because no controlled human trial (one comparing treated people with an untreated or placebo group) has been published.", "source_ids": [ "sikiric-2011", "gwyer-2019", "vasireddi-2025" ] }, { "q": "BPC-157 benefits: what does the evidence show?", "a": "In rats, BPC-157 sped healing of cut tendons, muscles, ligaments, bone, and gut lesions, and it increased tendon cell growth and migration in lab studies (animal-only evidence). In people, the only published data are three small uncontrolled reports from one clinic: 14 of 16 people reported less knee pain after injections, and 12 women with interstitial cystitis reported improvement after one bladder injection. With no comparison group, those results cannot separate the peptide from placebo or natural recovery, so the benefits in humans are unproven.", "source_ids": [ "chang-2011", "vasireddi-2025", "lee-2021", "lee-2024" ] }, { "q": "What are the side effects of BPC-157, and is it safe?", "a": "Nobody knows how safe it is in people, because there is no systematic human safety data. The three small pilot reports (about 30 people) reported no adverse events, and rodent studies did not report toxicity, but that is far too little data to rule out uncommon or long term harms. Anecdotal reports mention injection site irritation, nausea, and dizziness. Products sold as research chemicals add their own risk, because their identity, purity, and sterility are not verified.", "source_ids": [ "vasireddi-2025", "mcguire-2025", "lee-2025", "sikiric-2016" ] }, { "q": "Does BPC-157 cause cancer?", "a": "There is no evidence that it does, and no study has tested the question. The concern is theoretical: in rats and in human blood vessel cells BPC-157 increased new blood vessel growth and VEGFR2 signaling, and tumors depend on new blood vessels. Human follow-up is limited to a few dozen people over short periods, which could not detect a cancer signal. People with active or past cancer are the group the theoretical concern applies to most, and reviewers advise treating it as investigational.", "source_ids": [ "hsieh-2017", "mcguire-2025" ] }, { "q": "Oral BPC-157 vs injection: what did studies use?", "a": "Rodent studies gave BPC-157 by injection, in drinking water, and on the skin, and reported activity by mouth in animals. The human pilot reports all used injections (into the knee, the bladder wall, or a vein). No study has measured how much oral BPC-157, including the arginate salt form, is absorbed in people. In rats and dogs, injected BPC-157 had a half-life under 30 minutes and was quickly broken down into amino acids.", "source_ids": [ "sikiric-2011", "he-2022", "mcguire-2025" ] }, { "q": "Is BPC-157 FDA approved?", "a": "No. BPC-157 is not FDA approved for any use. FDA removed it from the 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list on July 23 to 24, 2026, but that vote is advisory. Until FDA publishes a final rule, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. Products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does BPC-157 help muscle growth?", "a": "No study shows that it does. The rodent muscle studies are about healing injured muscle, not building new muscle in healthy animals, and no human study has measured muscle size or strength. A 2025 systematic review noted increased growth hormone receptor expression in lab studies, which is often cited online, but that is a cell finding, not a measured gain in muscle. It is also prohibited at all times for tested athletes.", "source_ids": [ "vasireddi-2025", "wada-list" ] }, { "q": "Is BPC-157 banned by WADA?", "a": "Yes. BPC-157 is prohibited at all times under section S0 (non-approved substances) of the WADA Prohibited List, because it has no current approval by any government health authority for human use. Athletes subject to testing should not use it.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "21030672", "title": "The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration", "year": 2011, "design": "Rat Achilles tendon transection model plus tendon explant and fibroblast culture", "population": "Rats and rat tendon fibroblasts", "outcome": "BPC-157 increased tendon explant outgrowth, fibroblast survival under stress, and cell migration; healing was faster in treated rats", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/21030672/" }, { "pmid": "30915550", "title": "Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing", "year": 2019, "design": "Narrative review of animal and available human data", "population": "Rodent studies of tendon, ligament, and muscle healing", "outcome": "Consistent acceleration of soft tissue healing in rodents; human evidence limited to unpublished pilot work; authors call for human trials", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/30915550/" }, { "pmid": "27138887", "title": "Brain-gut axis and pentadecapeptide BPC 157: theoretical and practical implications", "year": 2016, "design": "Narrative review", "population": "Rodent models of gut, brain, and vascular injury", "outcome": "Summarizes proposed nitric oxide and growth factor mechanisms and cytoprotective effects across organ systems in animals", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/27138887/" }, { "pmid": "21548867", "title": "Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract", "year": 2011, "design": "Narrative review", "population": "Rodent models of gastrointestinal lesions and fistulas", "outcome": "Reports healing of NSAID induced ulcers, fistulas, and anastomoses in rodents; notes oral and parenteral activity", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/21548867/" }, { "pmid": "40756949", "title": "Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review", "year": 2025, "design": "Systematic review (36 studies: 35 preclinical, 1 clinical)", "population": "Animal models of muscle, tendon, ligament, and bone injury", "outcome": "Preclinical studies reported better functional, structural, and biomechanical healing; half-life under 30 minutes; no clinical safety data found", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/40756949/" }, { "pmid": "36588717", "title": "Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157 in rats and dogs", "year": 2022, "design": "Pharmacokinetic study after intravenous and intramuscular dosing", "population": "Rats and beagle dogs", "outcome": "Elimination half-life under 30 minutes; rapid metabolism into small peptide fragments and amino acids; excreted in urine and bile", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/36588717/" }, { "pmid": "34324435", "title": "Intra-articular injection of BPC 157 for multiple types of knee pain", "year": 2021, "design": "Retrospective chart review with phone survey, no control group", "n": 16, "population": "Adults with knee pain at one clinic", "outcome": "14 of 16 reported relief (11 of 12 given BPC-157 alone, 3 of 4 given it with thymosin beta-4); no validated outcome measures", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/34324435/" }, { "pmid": "39325560", "title": "Effect of BPC-157 on symptoms in patients with interstitial cystitis: a pilot study", "year": 2024, "design": "Uncontrolled single arm pilot", "n": 12, "population": "Women with interstitial cystitis unresponsive to pentosan polysulfate", "outcome": "All 12 reported symptom improvement after a single bladder wall injection; no adverse events reported; no control group", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/39325560/" }, { "pmid": "40131143", "title": "Safety of intravenous infusion of BPC157 in humans: a pilot study", "year": 2025, "design": "Uncontrolled safety pilot", "n": 2, "population": "Two healthy adults who had received the peptide before", "outcome": "No measurable change in heart, liver, kidney, thyroid, or glucose markers and no side effects reported over 3 days", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/40131143/" } ], "sources": [ { "id": "chang-2011", "type": "pubmed", "title": "The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration (J Appl Physiol 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21030672/", "pmid": "21030672", "year": 2011 }, { "id": "gwyer-2019", "type": "pubmed", "title": "Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing (Cell Tissue Res 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30915550/", "pmid": "30915550", "year": 2019 }, { "id": "sikiric-2016", "type": "pubmed", "title": "Brain-gut axis and pentadecapeptide BPC 157: theoretical and practical implications (Curr Neuropharmacol 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27138887/", "pmid": "27138887", "year": 2016 }, { "id": "sikiric-2011", "type": "pubmed", "title": "Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract (Curr Pharm Des 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21548867/", "pmid": "21548867", "year": 2011 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "lee-2021", "type": "pubmed", "title": "Lee E, Padgett B. Intra-articular injection of BPC 157 for multiple types of knee pain. Altern Ther Health Med 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34324435/", "pmid": "34324435", "year": 2021 }, { "id": "lee-2024", "type": "pubmed", "title": "Lee E, Walker C, Ayadi B. Effect of BPC-157 on symptoms in patients with interstitial cystitis: a pilot study. Altern Ther Health Med 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39325560/", "pmid": "39325560", "year": 2024 }, { "id": "lee-2025", "type": "pubmed", "title": "Lee E, Burgess K. Safety of intravenous infusion of BPC157 in humans: a pilot study. Altern Ther Health Med 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40131143/", "pmid": "40131143", "year": 2025 }, { "id": "he-2022", "type": "pubmed", "title": "He L et al. Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs. Front Pharmacol 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36588717/", "pmid": "36588717", "year": 2022 }, { "id": "hsieh-2017", "type": "pubmed", "title": "Hsieh MJ et al. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/27847966/", "pmid": "27847966", "year": 2017 }, { "id": "vasireddi-2025", "type": "pubmed", "title": "Vasireddi N et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review. HSS J 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40756949/", "pmid": "40756949", "year": 2025 }, { "id": "mcguire-2025", "type": "pubmed", "title": "McGuire FP et al. Regeneration or risk? A narrative review of BPC-157 for musculoskeletal healing. Curr Rev Musculoskelet Med 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40789979/", "pmid": "40789979", "year": 2025 } ], "related": [ "tb-500", "ghk-cu", "kpv", "peg-mgf" ], "cluster": "healing", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "BPC-157 benefits, side effects, and FDA status", "description": "BPC-157 benefits and side effects: what rodent studies and three small human reports show, the cancer question, oral vs injected forms, and 2026 FDA status.", "h1": "BPC-157 peptide", "headings": { "evidence": "BPC-157 benefits: what the evidence shows", "safety": "BPC-157 side effects" } } }, { "slug": "tb-500", "name": "TB-500 (thymosin beta-4)", "aliases": [ "Thymosin beta-4", "Tβ4", "Tbeta4", "TB4", "TB 500", "thymosin beta 4 fragment 17-23 (LKKTETQ)", "RGN-259 (ophthalmic thymosin beta-4)", "TB500", "TB-500 peptide", "Thymosin beta 4" ], "class": "Synthetic version or fragment of thymosin beta-4, a 43 amino acid actin sequestering peptide present in nearly all human cells", "one_liner": "Copy or fragment of the repair protein thymosin beta-4: strong animal data, small human trials of the full protein, no trial of injected TB-500; WADA banned.", "summary": "TB-500 is the name under which synthetic thymosin beta-4, a repair protein found in nearly all human cells, or its 7 amino acid active fragment, is sold for injection. Thymosin beta-4 itself has solid animal data for wound healing and cardiac repair and has small phase 1 and phase 2 human trials, which are early stage studies (IV safety, eye drops for dry eye, topical gel for skin ulcers), none of which tested injected TB-500 for injury healing. A 72 person dry eye trial missed its primary endpoints (its main goals), and two intravenous (into a vein) phase 1 studies in healthy volunteers found it well tolerated. No human trial of injected TB-500 exists, so PeptideAgent grades the injectable product animal-only. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and its advisory committee recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but no final rule has been published, and it is prohibited by WADA under section S2.", "mechanism": "Thymosin beta-4 is the main actin sequestering protein in mammalian cells, binding monomeric G-actin and regulating cytoskeletal assembly needed for cell migration. In animal models it promotes keratinocyte, endothelial, and cardiomyocyte migration, reduces inflammation and myofibroblast driven scarring, and forms a complex with PINCH and integrin linked kinase (ILK) that activates the survival kinase Akt. The 7 amino acid fragment LKKTETQ (residues 17 to 23) contains the actin binding motif and is what some TB-500 products claim to contain. These mechanisms are documented in rodent and cell work, not in humans receiving the injectable product.", "evidence_grade": "animal_only", "evidence_summary": "Rodent studies show thymosin beta-4 accelerates full thickness wound closure (reepithelialization up 42% at 4 days and 61% at 7 days in rats) and improves cardiac function after coronary ligation in mice. Human efficacy data come from small phase 2 trials of full-length thymosin beta-4: a 0.1% eye drop in 72 people with dry eye, where neither primary endpoint reached significance though some secondary endpoints did, and a topical gel in venous stasis and pressure ulcers, where a review of two trials reported faster healing in patients who healed. Two phase 1 studies of intravenous full length thymosin beta-4 in healthy volunteers found it well tolerated but did not test healing. No human trial of subcutaneous or intramuscular TB-500 for musculoskeletal injury has been published, and the identity of what is sold as TB-500 (full length peptide versus fragment) is not verified. The eye drop and intravenous studies used different formulations and purposes from injected TB-500; they are listed but do not raise the grade.", "human_evidence": "No indexed human trial of injected TB-500 products identified. The closest efficacy evidence is a single center, double masked, placebo controlled phase 2 trial of 0.1% thymosin beta-4 ophthalmic solution in 72 adults with moderate to severe dry eye for 28 days: the primary endpoints (ocular discomfort and inferior corneal staining) were not significantly different from placebo, while discomfort in the adverse environment challenge fell 27% relative to placebo and several other secondary endpoints improved. Two randomized, placebo controlled phase 1 studies gave intravenous full length thymosin beta-4 to healthy volunteers (40 people for 14 days in 2010, and 54 single dose plus 30 multiple dose participants in 2021) and reported only mild to moderate adverse events with no dose limiting toxicity; both were safety studies for heart attack drug development, not tests of healing. A review of two phase 2 trials of a topical thymosin beta-4 gel in venous stasis and pressure ulcers reported faster healing, by almost a month, in patients who healed. None of these studies tested injected TB-500 for muscle, tendon, or joint injury.", "animal_evidence": "In a rat full thickness wound model, thymosin beta-4 given topically or intraperitoneally increased reepithelialization by 42% at day 4 and up to 61% at day 7, increased wound contraction, collagen deposition, and angiogenesis, and stimulated keratinocyte migration 2 to 3 fold in vitro at picogram amounts. In mice with coronary artery ligation, thymosin beta-4 upregulated ILK and Akt activity, enhanced early cardiomyocyte survival, and improved cardiac function. Additional rodent and cell studies summarized in reviews report reduced scarring and fibrosis, and effects in corneal injury and brain injury models.", "conditions": [ "tendon-injury", "muscle-recovery", "wound-healing" ], "literature_dosing": "Not established in human literature for the injectable. Human studies tested thymosin beta-4 only as eye drops for dry eye and as intravenous infusions in phase 1 safety studies, and rodent wound studies used topical application or intraperitoneal injection; none of these translate to a human injectable dose, and no human dose finding study for TB-500 has been published.", "routes": [ "Subcutaneous or intramuscular injection (as sold)", "Topical eye drops (human dry eye trial, investigational)", "Topical to wound or intraperitoneal (animal studies)" ], "side_effects": [ "No human safety data for injected TB-500 products", "Two phase 1 intravenous studies of full length thymosin beta-4 in healthy volunteers: mild to moderate adverse events, no serious adverse events or dose limiting toxicity", "Eye drop trial: no significant safety findings over 28 days", "Injection site reactions, headache, and lethargy reported anecdotally", "Theoretical cancer concern: thymosin beta-4 drives cell migration and angiogenesis, and higher tumor levels are associated with invasion and metastasis in colorectal cancer studies (not shown to be caused by taking it)" ], "interactions": [ "No formal human interaction studies exist", "No specific drug interactions have been described in animal work" ], "contraindications": [ "Active cancer or history of cancer (theoretical cell migration and angiogenesis concern)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "under_review", "compounding_status": "Removed from the FDA 503A Category 2 list (substances nominated for compounding that raise significant safety risks) on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding TB-500 to the 503A bulks list. As of the last verification date FDA has not published a final rule listing it, so it is not on the 503A bulks list and a 503A pharmacy has no federal basis to compound it from bulk; state boards cannot authorize what federal law does not. It is not an FDA approved drug and is not eligible for 503B outsourcing. Products sold as research chemicals are not lawful for human use.", "typical_cost": "No lawful compounded price: TB-500 is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is TB-500?", "a": "TB-500 is the name used for synthetic thymosin beta-4, a 43 amino acid repair protein found in nearly all human cells, or for a short fragment of it. It is promoted for tendon, muscle, and wound healing on the strength of animal studies. It is not an FDA approved drug, it is named on the WADA Prohibited List (the World Anti-Doping Agency's banned list), and PeptideAgent grades the injectable product animal-only.", "source_ids": [ "goldstein-2012", "mendias-2026", "wada-list" ] }, { "q": "TB-500 benefits: what does the evidence show?", "a": "In animals, thymosin beta-4 clearly speeds wound closure (42% more reepithelialization at day 4 in rats) and improves heart function after injury in mice (animal-only evidence). In humans, full-length thymosin beta-4 has small phase 1 and phase 2 trials (IV safety, eye drops for dry eye, topical gel for skin ulcers): the 72 person dry eye trial missed its primary endpoints, and a review of two skin ulcer trials reported faster healing in patients who healed. No human trial of injected TB-500 for tendon, muscle, or ligament injury has been published, so the benefits people seek it for are unproven.", "source_ids": [ "malinda-1999", "bock-marquette-2004", "sosne-2015", "treadwell-2012" ] }, { "q": "What are the side effects of TB-500?", "a": "There is no human safety data for injected TB-500 products. The closest data come from two phase 1 studies of intravenous full length thymosin beta-4 in healthy volunteers, which reported mild to moderate adverse events and no serious ones, and a 28 day eye drop trial that raised no safety concerns. Anecdotal reports mention injection site irritation, headache, and lethargy. Unverified research chemical products add contamination and identity risks.", "source_ids": [ "ruff-2010", "wang-2021", "sosne-2015", "mendias-2026" ] }, { "q": "Does TB-500 cause cancer?", "a": "No study shows that taking it causes cancer, but the question has not been tested. The concern comes from tumor biology: thymosin beta-4 drives cell migration and blood vessel growth, and in colorectal cancer research higher thymosin beta-4 made cancer cells more invasive and was found at higher levels in liver metastases. That is an association in tumors, not proof that an injected dose causes harm, and the phase 1 studies were too short to detect a cancer signal. People with active or past cancer are the group the concern applies to most.", "source_ids": [ "wang-2004", "goldstein-2012", "ruff-2010" ] }, { "q": "TB-500 vs thymosin beta-4: are they the same?", "a": "Not necessarily. Thymosin beta-4 is a natural 43 amino acid protein. TB-500 is a trade style name used both for synthetic full length thymosin beta-4 and for a 7 amino acid fragment (LKKTETQ, residues 17 to 23) that contains its actin binding site. Sellers are inconsistent about which they supply, and the animal and human research used the full length peptide, so its results may not apply to fragment products.", "source_ids": [ "goldstein-2012", "mendias-2026" ] }, { "q": "Are there TB-500 capsules or nasal sprays?", "a": "Oral and nasal TB-500 products are marketed, but no human study has tested thymosin beta-4 by mouth or by nasal spray. The human studies used intravenous infusion, eye drops, and a topical gel on skin ulcers, and the animal wound and heart studies applied it to wounds or injected it. There is no evidence that a capsule or spray delivers the peptide to injured muscle, tendon, or skin.", "source_ids": [ "ruff-2010", "sosne-2015", "malinda-1999", "treadwell-2012" ] }, { "q": "Is TB-500 FDA approved?", "a": "No. TB-500 is not FDA approved for any use. FDA removed it from the 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026, but that vote is advisory. Until FDA publishes a final rule, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. Products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Is TB-500 banned by WADA?", "a": "Yes. The WADA Prohibited List names thymosin beta-4 and its derivatives, including TB-500, under section S2 (peptide hormones, growth factors, related substances and mimetics), prohibited at all times. Athletes subject to testing should not use it.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "10469335", "title": "Thymosin beta4 accelerates wound healing", "year": 1999, "design": "Rat full thickness wound model plus keratinocyte migration assay", "population": "Rats and cultured keratinocytes", "outcome": "Reepithelialization increased 42% at day 4 and up to 61% at day 7 versus saline; more contraction, collagen, and angiogenesis; keratinocyte migration up 2 to 3 fold", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/10469335/" }, { "pmid": "15565145", "title": "Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair", "year": 2004, "design": "Mouse coronary artery ligation model plus embryonic and postnatal cardiomyocyte culture", "population": "Mice and cultured cardiomyocytes", "outcome": "Thymosin beta-4 formed a complex with PINCH and ILK, activated Akt, enhanced early myocyte survival, and improved cardiac function after infarction", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/15565145/" }, { "pmid": "26056426", "title": "Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, phase II clinical trial", "year": 2015, "design": "Single center, double masked, placebo controlled phase 2 trial, 28 days of treatment", "n": 72, "population": "Adults with moderate to severe dry eye", "outcome": "Neither primary endpoint (ocular discomfort, inferior corneal staining) significantly different from placebo; several secondary endpoints improved, including 27% lower discomfort in the adverse environment challenge", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26056426/" }, { "pmid": "22074294", "title": "Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications", "year": 2012, "design": "Narrative review", "population": "Animal models of skin, eye, heart, and brain injury and early clinical programs", "outcome": "Summarizes actin binding, cell migration, anti-inflammatory, and anti-fibrotic mechanisms and the rationale for clinical trials in wounds, cornea, heart, and CNS", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/22074294/" }, { "pmid": "20536472", "title": "A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers", "year": 2010, "design": "Randomized, placebo controlled phase 1 ascending dose study, single dose then 14 daily doses", "n": 40, "population": "Healthy adult volunteers", "outcome": "Adverse events infrequent and mild to moderate; no dose limiting toxicity or serious adverse events; safety study only, healing not tested", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/20536472/" }, { "pmid": "34346165", "title": "A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin beta4 in healthy Chinese volunteers", "year": 2021, "design": "Randomized, double blind phase 1 study, single and multiple intravenous doses", "n": 84, "population": "Healthy adult volunteers (54 single dose, 30 multiple dose)", "outcome": "Adverse events mild to moderate; no dose limiting toxicity or serious adverse events; no accumulation with daily dosing; safety study only", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34346165/" } ], "sources": [ { "id": "malinda-1999", "type": "pubmed", "title": "Malinda KM et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10469335/", "pmid": "10469335", "year": 1999 }, { "id": "bock-marquette-2004", "type": "pubmed", "title": "Bock-Marquette I et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15565145/", "pmid": "15565145", "year": 2004 }, { "id": "sosne-2015", "type": "pubmed", "title": "Sosne G et al. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, phase II clinical trial. Clin Ophthalmol 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26056426/", "pmid": "26056426", "year": 2015 }, { "id": "goldstein-2012", "type": "pubmed", "title": "Goldstein AL et al. Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22074294/", "pmid": "22074294", "year": 2012 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics (names thymosin beta-4 and TB-500)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "ruff-2010", "type": "pubmed", "title": "Ruff D et al. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci 2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20536472/", "pmid": "20536472", "year": 2010 }, { "id": "wang-2021", "type": "pubmed", "title": "Wang X et al. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin beta4 in healthy Chinese volunteers. J Cell Mol Med 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34346165/", "pmid": "34346165", "year": 2021 }, { "id": "wang-2004", "type": "pubmed", "title": "Wang WS et al. Overexpression of the thymosin beta-4 gene is associated with increased invasion of SW480 colon carcinoma cells and the distant metastasis of human colorectal carcinoma. Oncogene 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15235586/", "pmid": "15235586", "year": 2004 }, { "id": "mendias-2026", "type": "pubmed", "title": "Mendias CL, Awan TM. Safety and efficacy of approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance. Sports Med 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41966639/", "pmid": "41966639", "year": 2026 }, { "id": "treadwell-2012", "type": "pubmed", "title": "Treadwell T et al. The regenerative peptide thymosin beta 4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23050815/", "pmid": "23050815", "year": 2012 } ], "related": [ "bpc-157", "ghk-cu", "peg-mgf", "kpv" ], "cluster": "healing", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "TB-500 peptide: evidence, side effects, legal status", "description": "TB-500 peptide explained: how it differs from thymosin beta-4, what the evidence shows, side effects, the cancer question, and its 2026 FDA status.", "h1": "TB-500 peptide (thymosin beta-4)", "headings": { "evidence": "TB-500 benefits: what the evidence shows", "safety": "TB-500 side effects" } } }, { "slug": "ghk-cu", "name": "GHK-Cu", "aliases": [ "Copper peptide", "GHK copper", "Glycyl-L-histidyl-L-lysine copper", "Gly-His-Lys-Cu", "copper tripeptide-1", "Prezatide copper", "GHK-Cu peptide", "GHK Cu", "GHKCu" ], "class": "Naturally occurring tripeptide (glycyl-histidyl-lysine) complexed with copper(II); found in human plasma, saliva, and urine", "one_liner": "Copper binding three amino acid peptide with decades of skin and wound data: lawful and well studied in skin cosmetics, unapproved and untested as an injection.", "summary": "GHK-Cu is a copper complex of a tripeptide (a chain of three amino acids) found naturally in human plasma (the liquid part of blood), discovered in 1973 and used in cosmetics since the 1990s. Applied to the skin it has animal wound healing data and small human cosmetic studies showing improved skin elasticity, firmness, and fine lines, mostly industry associated and summarized in reviews by its discoverer. It is lawful as a cosmetic ingredient, but the injectable form sold online is an unapproved drug with no human trial; FDA lists injectable GHK-Cu as a withdrawn 503A nomination, so it is off Category 2 (FDA's list of compounding ingredients with significant safety risks) but not on the bulks list of ingredients pharmacies may use.", "mechanism": "GHK binds copper(II) with an affinity similar to albumin's copper transport site and delivers it to cells. In cell and animal models GHK-Cu attracts macrophages, mast cells, and endothelial cells to injury sites, increases synthesis of collagen, elastin, glycosaminoglycans, and decorin, modulates matrix metalloproteinases and their inhibitors, and suppresses inflammatory signals including NF-kB and TNF-alpha. Gene expression studies suggest it shifts expression of a large number of human genes toward a repair profile. These mechanisms come from in vitro and animal work; human data are limited to skin outcomes.", "evidence_grade": "human_observational", "evidence_summary": "Animal studies show accelerated wound healing in rats, mice, pigs, and dogs. Human evidence consists of small controlled cosmetic studies of topical GHK-Cu creams reporting tighter skin, improved elasticity and density, fewer fine lines, and reduced photodamage, plus older reports in chronic wounds; these are summarized in reviews largely authored by the peptide's discoverer, and independent large randomized trials are lacking. The one small independent randomized trial identified (13 patients after laser resurfacing) found no objective benefit, only higher patient satisfaction; it tested a narrow use and does not raise the grade. There is no human trial of injected GHK-Cu for any indication.", "human_evidence": "Reviews report controlled studies in aged skin in which topical GHK-Cu creams tightened loose skin, improved elasticity, skin density, and firmness, reduced fine lines and wrinkles, and reduced photodamage and hyperpigmentation, and describe wound healing activity in humans. These studies are small, mostly cosmetic industry studies, and are cited through review articles rather than as independently indexed randomized trials. An independent randomized trial of GHK-Cu skin care after CO2 laser resurfacing (13 patients completed) found no difference in redness, wrinkles, or overall skin quality by blinded or computer assessment, though patients using GHK-Cu rated their skin higher. No indexed human trial of subcutaneous GHK-Cu identified.", "animal_evidence": "GHK-Cu accelerated healing of skin wounds, hair follicles, gastrointestinal tract, and bone in rodent and pig models, induced systemic wound healing in rats, mice, and pigs, and improved healing of foot pads in dogs. In vitro it increased fibroblast and keratinocyte proliferation, restored replicative vitality to fibroblasts after radiation, stimulated nerve outgrowth and angiogenesis, and increased hair follicle size.", "conditions": [ "skin-aging", "wound-healing" ], "literature_dosing": "Not established in human literature for injection. Human cosmetic studies applied topical creams and serums over 8 to 12 weeks according to the reviews; no human dose finding study for injected GHK-Cu exists.", "routes": [ "Topical cream or serum (cosmetic use, the only form with human data)", "Subcutaneous injection (as sold; no human data)", "Topical, intraperitoneal, and systemic (animal studies)" ], "side_effects": [ "Topical: generally well tolerated in cosmetic studies; occasional irritation or contact sensitivity", "Injectable: no systematic human safety data", "Injection site pain and irritation reported anecdotally", "Theoretical copper toxicity with large repeated injected doses (not documented)", "Theoretical concern that a peptide that stimulates angiogenesis and cell proliferation could affect existing tumors (reviews also report anti-cancer activity in vitro; unresolved)" ], "interactions": [ "No formal human interaction studies exist", "Topical vitamin C and strong acids may destabilize the copper complex in a formulation (formulation issue, not a drug interaction)" ], "contraindications": [ "Known copper metabolism disorder such as Wilson disease (theoretical, injected form)", "Pregnancy and breastfeeding for the injectable (no data)", "Competitive athletes should avoid the injectable pending clarification of WADA status" ], "wada_status": "unclear", "fda_status": "category_2_removed", "compounding_status": "GHK-Cu has two regulatory tracks. As a cosmetic ingredient in topical products it is lawfully marketed without FDA premarket approval, provided no drug claims are made. As an injectable drug it is not FDA approved and is not a component of any approved drug. GHK-Cu for injectable routes was nominated for the 503A bulks list and placed in 503A Category 2; the FDA Category 2 page current as of April 22, 2026 now lists it under bulk drug substances nominated but withdrawn, so it is no longer in Category 2 but is not on the bulks list and was not reviewed by the Pharmacy Compounding Advisory Committee in July 2026. Because it is not on the bulks list, a 503A pharmacy has no federal basis to compound injectable GHK-Cu from bulk, and state boards cannot authorize what federal law does not. Injectable products sold as research chemicals are not lawful for human use.", "typical_cost": "Topical cosmetic serums and creams roughly 20 to 100 USD per bottle. There is no lawful compounded price for injectable GHK-Cu: it is off 503A Category 2 but is not on the 503A bulks list and was not recommended by PCAC in July 2026. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Topical cosmetic products containing GHK-Cu are sold over the counter without a prescription, as long as they make only cosmetic claims.", "No lawful compounded path for injectable GHK-Cu today: FDA lists it as a withdrawn 503A nomination, so it is off Category 2 but not on the 503A bulks list, and a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved drug; injectable products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "What does GHK-Cu do?", "a": "GHK-Cu is a small peptide from human plasma (the liquid part of blood) that binds copper and delivers it to cells. In cell and animal studies it draws repair cells to wounds, increases production of collagen, elastin, and glycosaminoglycans (the proteins and gel-like molecules that give skin its structure), and dampens inflammatory signals, and animal wounds heal faster with it. In people, the evidence is limited to skin products applied to the surface, where small cosmetic studies report firmer, more elastic skin and fewer fine lines.", "source_ids": [ "pickart-2008", "pickart-2015", "pickart-2018" ] }, { "q": "Are copper peptides the same as GHK-Cu?", "a": "Mostly, but not always. Copper peptide is a skin care label for ingredients that pair copper with a short peptide, and GHK-Cu (listed on labels as copper tripeptide-1) is the one the research is about. A product sold as copper peptides may contain GHK-Cu at an unstated strength or a different copper complex, and results from GHK-Cu studies apply only to GHK-Cu.", "source_ids": [ "pickart-2015", "pickart-2008" ] }, { "q": "Topical vs injected GHK-Cu: what do studies cover?", "a": "Every human study is topical. Reviews summarize small cosmetic studies of creams and serums in aged or sun damaged skin, and one independent randomized trial after laser resurfacing found no objective improvement over skin care without GHK-Cu, only higher patient satisfaction. Injected GHK-Cu has animal data from systemic dosing but no human study of any kind, so its effects and safety in people are unknown. Topical products are lawful cosmetics; the injectable has no lawful compounded path.", "source_ids": [ "pickart-2015", "miller-2006", "pickart-2018", "fda-503a-bulks" ] }, { "q": "What are the side effects of GHK-Cu, and is it safe?", "a": "Topical GHK-Cu is generally well tolerated in cosmetic studies, with occasional irritation. The injectable has no systematic human safety data; anecdotal reports mention injection site pain, and copper overload from repeated large injected doses is a theoretical concern. Reviews report both pro-repair and anti-cancer activity in cell studies, so the effect on existing tumors is unresolved. Unapproved injectable products also carry identity and purity risks.", "source_ids": [ "pickart-2018", "pickart-2015", "mendias-2026" ] }, { "q": "Is GHK-Cu FDA approved?", "a": "No. GHK-Cu is not an FDA approved drug and not a component of one. As a cosmetic ingredient in creams and serums it is lawfully sold without FDA approval as long as the products make only cosmetic claims. Injectable GHK-Cu is a withdrawn 503A nomination: it is off Category 2 but not on the 503A bulks list and was not reviewed by the advisory committee in July 2026, so a 503A pharmacy has no federal basis to compound it from bulk. Injectable vials sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-cosmetics-vs-drugs" ] }, { "q": "Does GHK-Cu work for skin aging and wrinkles?", "a": "The topical evidence is encouraging but thin. Reviews describe controlled cosmetic studies in which GHK-Cu creams tightened loose skin, improved elasticity, firmness, and density, and reduced fine lines, wrinkles, and photodamage over 8 to 12 weeks. Those studies are small, industry associated, and cited through reviews written by the peptide's discoverer, and the one independent randomized trial identified found no objective benefit after laser resurfacing. PeptideAgent grades the evidence human-observational.", "source_ids": [ "pickart-2015", "pickart-2008", "miller-2006" ] }, { "q": "Does GHK-Cu help hair growth?", "a": "Reviews report that GHK-Cu increases hair follicle size in animal and ex vivo models, which is the basis for copper peptide hair products. No indexed randomized human trial of GHK-Cu for hair loss was identified, so the human claim is unproven.", "source_ids": [ "pickart-2008", "pickart-2015" ] }, { "q": "Is GHK-Cu banned by WADA?", "a": "It is not named on the WADA Prohibited List, and a topical cosmetic is not a doping concern. Injected GHK-Cu is a pharmacological substance with no approval by any health authority for therapeutic use, which is the definition WADA uses for section S0 (non-approved substances), so athletes should treat the injectable as prohibited and check with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "29986520", "title": "Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data", "year": 2018, "design": "Narrative review", "population": "Cell, animal, and human skin studies", "outcome": "Summarizes wound healing across skin, lung, bone, liver, and stomach in animals, and gene expression data suggesting broad regulation of repair and inflammation pathways", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/29986520/" }, { "pmid": "26236730", "title": "GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration", "year": 2015, "design": "Narrative review", "population": "Animal wound models and human cosmetic studies of topical GHK-Cu", "outcome": "Reports accelerated wound healing in rats, mice, pigs, and dogs and cosmetic study findings of tighter skin, improved elasticity and density, and fewer fine lines and wrinkles", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26236730/" }, { "pmid": "18644225", "title": "The human tri-peptide GHK and tissue remodeling", "year": 2008, "design": "Narrative review", "population": "Cell, animal, and human studies of GHK and GHK-Cu", "outcome": "Describes chemoattraction of repair cells, anti-inflammatory effects, increased collagen and elastin synthesis, and controlled studies in aged skin showing improved firmness and fewer wrinkles", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/18644225/" }, { "pmid": "16847171", "title": "Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin", "year": 2006, "design": "Randomized trial with blinded evaluators, 12 weeks", "n": 13, "population": "Adults after circumoral CO2 laser resurfacing", "outcome": "No significant difference in redness, wrinkles, or overall skin quality by blinded or computer assessment; higher patient rated skin quality with GHK-Cu", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16847171/" } ], "sources": [ { "id": "pickart-2018", "type": "pubmed", "title": "Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. Int J Mol Sci 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29986520/", "pmid": "29986520", "year": 2018 }, { "id": "pickart-2015", "type": "pubmed", "title": "Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. Biomed Res Int 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26236730/", "pmid": "26236730", "year": 2015 }, { "id": "pickart-2008", "type": "pubmed", "title": "Pickart L. The human tri-peptide GHK and tissue remodeling. J Biomater Sci Polym Ed 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18644225/", "pmid": "18644225", "year": 2008 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-cosmetics-vs-drugs", "type": "fda", "title": "FDA: Is it a cosmetic, a drug, or both? (or is it soap?)", "url": "https://www.fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-drug-or-both-or-it-soap", "year": 2024 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "miller-2006", "type": "pubmed", "title": "Miller TR et al. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16847171/", "pmid": "16847171", "year": 2006 }, { "id": "mendias-2026", "type": "pubmed", "title": "Mendias CL, Awan TM. Safety and efficacy of approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance. Sports Med 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41966639/", "pmid": "41966639", "year": 2026 } ], "related": [ "bpc-157", "tb-500", "kpv", "epitalon" ], "cluster": "healing", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "GHK-Cu (copper peptide): evidence and legal status", "description": "What GHK-Cu copper peptide does, topical vs injected evidence, side effects, and FDA status. Topical creams are lawful cosmetics; injectable GHK-Cu is not.", "h1": "GHK-Cu (copper peptide)", "headings": { "evidence": "GHK-Cu benefits: topical vs injected, what studies cover", "safety": "GHK-Cu side effects" } } }, { "slug": "kpv", "name": "KPV", "aliases": [ "Lys-Pro-Val", "alpha-MSH (11-13)", "alpha-MSH C-terminal tripeptide", "lysine-proline-valine", "KPV peptide", "KPV tripeptide" ], "class": "Synthetic tripeptide (lysine-proline-valine), the C-terminal fragment of alpha-melanocyte stimulating hormone (alpha-MSH)", "one_liner": "Anti-inflammatory fragment of the hormone alpha-MSH; mouse colitis data, no human trial; recommended for FDA's compounding list in July 2026, rule pending.", "summary": "KPV is the three amino acid tail fragment of alpha-MSH, a natural skin darkening hormone, that keeps the parent hormone's anti-inflammatory activity without its pigmentation effects. In mouse models of colitis (an inflamed colon), oral KPV reduced inflammation, weight loss, and tissue damage seen under the microscope, and in cell studies very low (nanomolar) concentrations block NF-kB signaling, a main switch for inflammation. No human trial exists, so its evidence grade is animal-only. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but no final rule has been published.", "mechanism": "KPV is taken into intestinal epithelial and immune cells by the PepT1 di/tripeptide transporter, which is induced in the colon during inflammatory bowel disease. Inside cells it inhibits activation of NF-kB and MAP kinase pathways and reduces secretion of pro-inflammatory cytokines. Unlike full length alpha-MSH, KPV does not require the melanocortin-1 receptor for its anti-inflammatory effect (it worked in mice lacking a functional MC1 receptor) and does not stimulate pigmentation. These mechanisms are from cell and mouse studies.", "evidence_grade": "animal_only", "evidence_summary": "Two independent 2008 mouse studies showed that KPV reduces intestinal inflammation. Oral KPV in drinking water reduced the incidence and severity of DSS and TNBS induced colitis with lower pro-inflammatory cytokine expression, and in DSS and T cell transfer colitis KPV led to earlier recovery, regained body weight, reduced inflammatory infiltrates, and lower myeloperoxidase activity. Later mouse work from one of the same groups found that KPV reduced colitis associated tumor formation and that KPV packaged in targeted nanoparticles eased colitis. No indexed human trial of KPV for any indication has been published.", "human_evidence": "No indexed human trial identified. KPV is sold for inflammatory bowel symptoms, skin inflammation, and general anti-inflammatory use on the strength of mouse data and the known biology of alpha-MSH; no human dose finding, safety, or efficacy study has been published.", "animal_evidence": "In mice, KPV added to drinking water reduced DSS and TNBS induced colitis, with lower histologic damage and pro-inflammatory cytokine mRNA; the effect was mediated by PepT1 uptake. In a second laboratory, KPV in DSS colitis produced earlier recovery and significantly stronger regain of body weight, reduced inflammatory infiltrates and myeloperoxidase activity, and also produced recovery in CD45RB(hi) T cell transfer colitis; it rescued all animals in the treatment group of mice lacking a functional MC1 receptor, showing the effect is independent of that receptor. In a mouse model of colitis associated cancer, KPV prevented tumor formation in normal mice but not in mice lacking PepT1, and oral KPV delivered in hyaluronic acid coated nanoparticles reduced mucosal damage and TNF-alpha in mouse ulcerative colitis.", "conditions": [ "inflammation" ], "literature_dosing": "Not established in human literature. Mouse colitis studies gave KPV orally in drinking water, in nanoparticles, or by injection; animal doses do not translate to a human dose, and no human study has been published.", "routes": [ "Oral capsule (as sold)", "Subcutaneous injection (as sold)", "Topical cream and nasal spray (as sold)", "Oral in drinking water and intraperitoneal (mouse studies)" ], "side_effects": [ "No systematic human safety data", "No toxicity reported at the doses used in mouse studies", "Injection site reactions reported anecdotally", "Because it dampens NF-kB driven immune signaling, a theoretical concern about impaired response to infection exists (not demonstrated)" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive immune suppression with corticosteroids, biologics, or other immunosuppressants (not studied)" ], "contraindications": [ "Active serious infection (theoretical, given immune dampening)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited under S0)" ], "wada_status": "prohibited", "fda_status": "under_review", "compounding_status": "Removed from the FDA 503A Category 2 list on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding KPV to the 503A bulks list. As of the last verification date FDA has not published a final rule listing it, so it is not on the 503A bulks list and a 503A pharmacy has no federal basis to compound it from bulk; state boards cannot authorize what federal law does not. It is not an FDA approved drug and is not eligible for 503B outsourcing. Products sold as research chemicals or as dietary supplements are not lawful for human drug use.", "typical_cost": "No lawful compounded price: KPV is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is KPV peptide?", "a": "KPV is a three amino acid peptide (lysine, proline, valine) cut from the end of alpha-MSH, a natural hormone. It keeps the hormone's anti-inflammatory activity without darkening skin, and it is studied mainly for gut inflammation. It is not an FDA approved drug, and PeptideAgent grades its evidence animal-only because no human trial has been published.", "source_ids": [ "kannengiesser-2008", "dalmasso-2008" ] }, { "q": "KPV peptide benefits: what does the evidence show?", "a": "In mice, oral KPV reduced chemically induced and T cell driven colitis in two independent 2008 studies, with less weight loss, less tissue damage, and lower inflammatory cytokines. Later mouse work found it prevented colitis associated tumors and that targeted KPV nanoparticles eased colitis. All of this is animal-only evidence: no human trial of KPV for gut, skin, or any other condition has been published, so its benefits in people are unproven.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008", "viennois-2016", "xiao-2017" ] }, { "q": "What are the side effects of KPV?", "a": "There is no systematic human safety data. Mouse studies did not report toxicity. Anecdotal reports mention injection site irritation for the injectable form. Because KPV suppresses NF-kB driven inflammatory signaling, a theoretical concern about blunted responses to infection exists but has not been studied. Unlike full length alpha-MSH or melanotan peptides, it does not darken skin.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008" ] }, { "q": "Oral KPV vs injection: what did studies use?", "a": "The mouse colitis studies mostly gave KPV by mouth, in drinking water or in nanoparticles designed to reach the colon, because gut cells take it up through the PepT1 transporter that inflammation switches on. Products are also sold as injections, creams, and nasal sprays, none of which has been studied in people. No human dose has been established for any route.", "source_ids": [ "dalmasso-2008", "xiao-2017" ] }, { "q": "Is KPV FDA approved?", "a": "No. KPV is not FDA approved for any use. FDA removed it from the 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026, but that vote is advisory. Until FDA publishes a final rule, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. Products sold as research chemicals or supplements are not lawful for human drug use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Is KPV banned by WADA?", "a": "Yes, by default. KPV is not named on the WADA Prohibited List, but it has no approval from any government health authority for human use, so it falls under section S0 (non-approved substances) and is prohibited at all times. Athletes subject to testing should not use it.", "source_ids": [ "wada-list" ] }, { "q": "KPV vs BPC-157: which is better for gut healing?", "a": "Neither has human trial data. BPC-157 has a larger rodent literature covering ulcers, fistulas, and NSAID injury, while KPV has two mouse colitis studies focused on immune driven inflammation rather than tissue repair. Both were removed from the FDA Category 2 list in April 2026 and recommended for the 503A bulks list in July 2026. They are often sold together, a combination never tested in humans.", "source_ids": [ "dalmasso-2008", "fda-pcac-2026" ] }, { "q": "Is KPV the same as alpha-MSH or melanotan?", "a": "No. KPV is only the last three amino acids of alpha-MSH. It keeps the anti-inflammatory activity but, in mice, works without the melanocortin-1 receptor, so it does not cause the tanning that alpha-MSH and the melanotan peptides do. It is a different compound with a different (and much smaller) evidence base.", "source_ids": [ "kannengiesser-2008" ] } ], "studies": [ { "pmid": "18061177", "title": "PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation", "year": 2008, "design": "In vitro epithelial and T cell assays plus DSS and TNBS induced colitis in mice", "population": "Human intestinal epithelial and T cell lines; mice with chemically induced colitis", "outcome": "Nanomolar KPV inhibited NF-kB and MAP kinase signaling and cytokine secretion via PepT1 uptake; oral KPV reduced incidence and severity of colitis with lower pro-inflammatory cytokine expression", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/18061177/" }, { "pmid": "18092346", "title": "Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease", "year": 2008, "design": "DSS colitis and CD45RB(hi) T cell transfer colitis in mice, including MC1 receptor deficient mice", "population": "Mice with induced colitis", "outcome": "KPV led to earlier recovery, stronger regain of body weight, reduced inflammatory infiltrates and myeloperoxidase activity; effect independent of the MC1 receptor", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/18092346/" }, { "pmid": "27458604", "title": "Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model", "year": 2016, "design": "AOM/DSS colitis associated cancer model in wild type, PepT1 overexpressing, and PepT1 knockout mice", "population": "Mice", "outcome": "KPV prevented colitis associated tumor formation in wild type mice but had no effect in PepT1 knockout mice", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/27458604/" }, { "pmid": "28143741", "title": "Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis", "year": 2017, "design": "Nanoparticle formulation study plus mouse ulcerative colitis model", "population": "Mice with induced colitis and cultured colon and immune cells", "outcome": "Oral KPV nanoparticles in a hydrogel reduced mucosal damage and TNF-alpha and outperformed a non targeted KPV nanoparticle system", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/28143741/" } ], "sources": [ { "id": "dalmasso-2008", "type": "pubmed", "title": "Dalmasso G et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18061177/", "pmid": "18061177", "year": 2008 }, { "id": "kannengiesser-2008", "type": "pubmed", "title": "Kannengiesser K et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18092346/", "pmid": "18092346", "year": 2008 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "viennois-2016", "type": "pubmed", "title": "Viennois E et al. Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model. Cell Mol Gastroenterol Hepatol 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27458604/", "pmid": "27458604", "year": 2016 }, { "id": "xiao-2017", "type": "pubmed", "title": "Xiao B et al. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Mol Ther 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28143741/", "pmid": "28143741", "year": 2017 } ], "related": [ "bpc-157", "tb-500", "thymosin-alpha-1", "melanotan-ii" ], "cluster": "healing", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "KPV peptide: benefits, evidence, and legal status", "description": "What KPV peptide is, what the mouse colitis studies show about its benefits, known side effects, and why there is no lawful compounded KPV in 2026.", "h1": "KPV peptide", "headings": { "evidence": "KPV peptide benefits: what the evidence shows", "safety": "KPV side effects" } } }, { "slug": "peg-mgf", "name": "PEG-MGF", "aliases": [ "Pegylated mechano growth factor", "MGF", "Mechano growth factor", "IGF-1Ec E-domain peptide", "IGF-1Eb (rodent MGF)", "MGF E-peptide" ], "class": "Pegylated synthetic 24 amino acid peptide copying the E domain of mechano growth factor, a splice variant of IGF-1 (IGF-1Ec in humans) expressed in muscle after mechanical loading or damage", "one_liner": "PEG-coated fragment of a muscle form of the growth factor IGF-1: cell and mouse data only, no human trial of the peptide, and named on WADA's banned list.", "summary": "PEG-MGF is a synthetic copy of the E domain (end section) of mechano growth factor, an alternate form of the growth factor IGF-1 that human muscle makes briefly after resistance exercise or injury, with PEG attached (pegylated) so it lasts longer in the body. In cell studies the E domain peptide increases myoblast (muscle precursor cell) proliferation and delays their maturation, and in mice it preserved heart function after infarction (a heart attack), but no human trial of the synthetic peptide exists, so its evidence grade is animal-only. It has never been approved by FDA, its 503A nomination was withdrawn so it is off Category 2 (FDA's list of compounding ingredients with significant safety risks) but not on the bulks list of ingredients pharmacies may use, it cannot lawfully be compounded, and mechano growth factors are named on the WADA Prohibited List under section S2.", "mechanism": "Mechanical loading or damage of muscle shifts IGF-1 gene splicing toward the MGF isoform for roughly a day, after which splicing returns to the systemic IGF-1Ea form. The MGF E domain is thought to activate muscle satellite (stem) cells and increase myoblast proliferation while inhibiting terminal differentiation, acting through a receptor other than the IGF-1 receptor (blocking the IGF-1 receptor with an antibody did not remove the effect). Pegylation extends the half life of the otherwise rapidly cleared peptide. Whether an injected synthetic E domain peptide reproduces the effects of locally spliced MGF in humans has never been tested.", "evidence_grade": "animal_only", "evidence_summary": "Evidence is limited to in vitro myoblast studies, rodent muscle expression studies, one mouse myocardial infarction study of a synthetic E domain peptide, and human biopsy studies showing that MGF mRNA rises after resistance exercise in young but not elderly subjects. No human study has given PEG-MGF or any synthetic MGF peptide to people, and the pegylated product sold online has no published pharmacology at all. The human biopsy studies measured endogenous MGF expression and did not administer the peptide; they are listed but do not raise the grade.", "human_evidence": "No indexed human trial of PEG-MGF or any synthetic MGF peptide identified. The only human data are on the natural gene product: in 15 subjects (8 young, 7 elderly), MGF mRNA in quadriceps biopsies rose significantly 2.5 hours after high resistance exercise in the young group but not in the elderly, and resting MGF levels were about 100 fold lower than the IGF-1Ea isoform.", "animal_evidence": "In cultured myoblasts the MGF E domain increased proliferation and inhibited terminal differentiation, unlike mature IGF-1, and the effect persisted when the IGF-1 receptor was blocked. In mice, a synthetic MGF E domain peptide given at the time of myocardial infarction inhibited apoptosis, prevented pathologic hypertrophy, and preserved systolic and diastolic function at 2 weeks. Reviews describe MGF as a local muscle growth and repair factor whose expression falls with age and in dystrophic muscle.", "conditions": [ "muscle-recovery" ], "literature_dosing": "Not established in human literature. No human study has administered PEG-MGF or any synthetic MGF peptide. The mouse cardiac study used a synthetic E domain peptide at doses reported per animal that do not translate to humans.", "routes": [ "Subcutaneous or intramuscular injection (as sold)", "Intraperitoneal or intravenous (mouse study)" ], "side_effects": [ "No human safety data of any kind", "Injection site pain and swelling reported anecdotally", "Theoretical concern about promoting growth of existing tumors, shared with IGF-1 family peptides (not studied)", "Hypoglycemia is a class concern for IGF-1 related peptides, though the E domain acts through a different receptor and this has not been assessed" ], "interactions": [ "No formal human interaction studies exist", "Often stacked with IGF-1 LR3 or growth hormone secretagogues in gray market use; no combination has been studied" ], "contraindications": [ "Active cancer or history of cancer (theoretical growth factor concern)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Never reviewed or approved by FDA for any use. PEG-MGF (mechano growth factor, pegylated) was nominated for the 503A bulks list and placed in 503A Category 2; the FDA Category 2 page current as of April 22, 2026 now lists it under bulk drug substances nominated but withdrawn, so it is no longer in Category 2 but is not on the bulks list and has no active nomination. It is not a component of an approved drug and has no USP monograph, so a 503A pharmacy has no lawful basis to compound it, and it is not eligible for 503B outsourcing. It is available only as a research chemical, which is not lawful for human use.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date; the 503A nomination was withdrawn and it is not on the bulks list.", "Not available as an FDA approved product and not eligible for 503B outsourcing.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is PEG-MGF legal?", "a": "It is not an FDA approved drug. It was nominated for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) and placed in Category 2 (ingredients flagged for significant safety risks), and FDA now lists it as a withdrawn nomination; it cannot be compounded because it is not a component of an approved drug and is not on the 503A bulks list. The only products on the market are research chemicals, which are not lawful for human use. Possession is not a crime, but no licensed channel can lawfully supply it for injection.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Does PEG-MGF build muscle?", "a": "Nobody knows in humans. The natural MGF splice variant rises in muscle for about a day after heavy exercise and, in cell studies, its E domain makes muscle precursor cells multiply. But no human has been given synthetic PEG-MGF in a published study, and the elderly muscle that would benefit most did not even raise its own MGF after exercise in the one human biopsy study. PeptideAgent grades the evidence animal-only.", "source_ids": [ "yang-2002", "hameed-2003", "goldspink-2005" ] }, { "q": "What are the side effects of PEG-MGF?", "a": "There are no human safety data at all. Anecdotal reports mention injection site pain and swelling. Because it belongs to the IGF-1 family, theoretical concerns include stimulating existing tumors and, less likely given its separate receptor, hypoglycemia. None of this has been studied.", "source_ids": [ "yang-2002", "carpenter-2013" ] }, { "q": "How is PEG-MGF taken?", "a": "Products sold online are lyophilized vials for subcutaneous or intramuscular injection, and the pegylation is claimed to extend the half life from minutes to hours or days. No human dosing study exists, so any regimen is invented rather than measured. The one animal study of a synthetic E domain peptide was in mice after heart attack, not in muscle building.", "source_ids": [ "carpenter-2013" ] }, { "q": "How much does PEG-MGF cost?", "a": "There is no licensed source and therefore no legitimate price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is PEG-MGF banned by WADA?", "a": "Yes, explicitly. The WADA Prohibited List names mechano growth factors (MGFs) under section S2 (peptide hormones, growth factors, related substances and mimetics), prohibited at all times in and out of competition. Athletes subject to testing should not use it.", "source_ids": [ "wada-list" ] }, { "q": "PEG-MGF vs IGF-1 LR3: what is the difference?", "a": "Both are IGF-1 family research peptides with no human trials and both are WADA prohibited. IGF-1 LR3 is a full length IGF-1 analog that binds the IGF-1 receptor and has strong anabolic effects in rats; PEG-MGF is only the E domain of the MGF splice variant, acts through a different, unidentified receptor, and is thought to expand muscle precursor cells rather than drive growth directly. Neither is lawfully available for human use.", "source_ids": [ "yang-2002", "wada-list" ] } ], "studies": [ { "pmid": "12095637", "title": "Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation", "year": 2002, "design": "In vitro myoblast culture", "population": "Cultured muscle cells", "outcome": "The MGF E domain increased myoblast proliferation and inhibited terminal differentiation, unlike mature IGF-1, through a receptor other than the IGF-1 receptor", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/12095637/" }, { "pmid": "12562960", "title": "Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise", "year": 2003, "design": "Human muscle biopsy study before and after a single bout of resistance exercise", "n": 15, "population": "8 young (25 to 36 years) and 7 elderly (70 to 82 years) subjects", "outcome": "MGF mRNA rose significantly 2.5 hours after exercise in young but not elderly subjects; resting MGF was about 100 fold lower than IGF-1Ea", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/12562960/" }, { "pmid": "23712705", "title": "The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction", "year": 2013, "design": "Cell stress assays plus mouse myocardial infarction model", "population": "H9c2 cardiac cells and mice after coronary ligation", "outcome": "Synthetic E domain peptide inhibited apoptosis in vitro and, given at infarction, preserved systolic and diastolic function and reduced apoptotic nuclei at 2 weeks", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/23712705/" }, { "pmid": "16024511", "title": "Mechanical signals, IGF-I gene splicing, and muscle adaptation", "year": 2005, "design": "Narrative review", "population": "Animal and human studies of IGF-1 splicing in muscle", "outcome": "Describes MGF as a local growth and repair factor that kick starts hypertrophy after resistance exercise and whose expression is impaired in old age and disease", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/16024511/" } ], "sources": [ { "id": "yang-2002", "type": "pubmed", "title": "Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett 2002", "url": "https://pubmed.ncbi.nlm.nih.gov/12095637/", "pmid": "12095637", "year": 2002 }, { "id": "hameed-2003", "type": "pubmed", "title": "Hameed M et al. Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise. J Physiol 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12562960/", "pmid": "12562960", "year": 2003 }, { "id": "carpenter-2013", "type": "pubmed", "title": "The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction. Mol Cell Biochem 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23712705/", "pmid": "23712705", "year": 2013 }, { "id": "goldspink-2005", "type": "pubmed", "title": "Goldspink G. Mechanical signals, IGF-I gene splicing, and muscle adaptation. Physiology (Bethesda) 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/16024511/", "pmid": "16024511", "year": 2005 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (names mechano growth factors)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "igf-1-lr3", "follistatin-344", "bpc-157", "tb-500" ], "cluster": "healing", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "ara-290", "name": "ARA-290 (cibinetide)", "aliases": [ "Cibinetide", "ARA 290", "ARA290", "pyroglutamate helix B surface peptide", "pHBSP", "innate repair receptor agonist" ], "class": "Investigational 11 amino acid peptide derived from the helix B surface of erythropoietin, engineered to activate the innate repair receptor without stimulating red blood cell production", "one_liner": "Erythropoietin derived peptide with small placebo controlled trials in sarcoidosis and diabetic neuropathy; investigational, not approved, WADA prohibited.", "summary": "ARA-290 (cibinetide) is an investigational peptide copied from a surface region of erythropoietin that activates a tissue protective receptor without raising hemoglobin. In small randomized placebo controlled trials in sarcoidosis associated small fiber neuropathy (n = 22 and n = 64) and in type 2 diabetes with neuropathy, 28 days of daily injections improved neuropathic symptoms and increased corneal nerve fiber density. It is not approved by FDA or any other regulator, so it cannot be compounded and is prohibited in sport under WADA section S0.", "mechanism": "Erythropoietin has two receptor systems: the classic homodimeric receptor that drives red cell production, and a heteromeric innate repair receptor (erythropoietin receptor plus the beta common receptor) expressed on injured tissue that mediates anti-inflammatory and tissue protective effects. ARA-290 copies helix B of erythropoietin and binds only the repair receptor, so it protects and repairs tissue in animal models without the thrombosis and hypertension risks of erythropoietin. It has a plasma half life of only minutes but a sustained biological effect.", "evidence_grade": "human_rct", "evidence_summary": "Several small phase 2 randomized controlled trials from a single development program. In 22 sarcoidosis patients with small fiber neuropathy, 4 weeks of intravenous ARA-290 improved the small fiber neuropathy screening list score more than placebo (minus 11.5 versus minus 2.9 points). A second placebo controlled trial of 28 days of subcutaneous dosing improved symptoms and increased corneal nerve fiber density. A phase 2b trial of 64 patients found a significant increase in corneal nerve fiber area at 4 mg per day. In type 2 diabetes with neuropathy, 28 days of 4 mg daily improved HbA1c, lipids, and PainDetect scores. All trials were short, small, and sponsored by the developer; no phase 3 trial has reported.", "human_evidence": "Heij 2012: 22 sarcoidosis patients with small fiber neuropathy symptoms, double blind, ARA-290 2 mg intravenously three times weekly (n = 12) or placebo (n = 10) for 4 weeks; screening list score improved minus 11.5 versus minus 2.9, with improvements in SF-36 pain and physical functioning, and no safety concerns. Dahan 2013: blinded placebo controlled trial of 28 days of daily subcutaneous ARA-290 in sarcoidosis small fiber neuropathy; improved neuropathic symptoms, increased corneal nerve fiber density, improved temperature sensitivity and 6 minute walk. Culver 2017: 64 patients, phase 2b, cibinetide 1, 4, or 8 mg daily versus placebo for 28 days; placebo corrected corneal nerve fiber area increased 697 square micrometers at 4 mg (P = 0.012) with more regenerating skin fibers. Brines 2015: type 2 diabetes with painful neuropathy, 4 mg daily subcutaneously versus placebo for 28 days; improved HbA1c, lipids, and PainDetect score, and increased corneal nerve fiber density in those with low baseline density.", "animal_evidence": "ARA-290 reduced allodynia in preclinical neuropathy models and showed tissue protection in rodent models of ischemia, inflammation, and metabolic injury, without increasing hematocrit. These findings underpinned the human program.", "conditions": [ "inflammation" ], "literature_dosing": "Trial regimens only: 2 mg intravenously three times weekly for 4 weeks (Heij 2012); 4 mg subcutaneously once daily for 28 days (Brines 2015); 1, 4, or 8 mg subcutaneously once daily for 28 days (Culver 2017), with 4 mg the most effective dose. No approved label exists.", "routes": [ "Subcutaneous injection once daily (phase 2 trials)", "Intravenous infusion (early pilot trial)" ], "side_effects": [ "No safety concerns raised by clinical or laboratory assessments in the 28 day trials", "Does not raise hemoglobin or hematocrit, by design", "Injection site reactions", "Long term safety unknown; no trial exceeded a few weeks of dosing", "Products sold online as ARA-290 are unverified and carry the usual risks of unregulated injectables" ], "interactions": [ "No formal interaction studies published", "Theoretical additive effect with erythropoiesis stimulating agents on the shared receptor subunit (not studied)" ], "contraindications": [ "Not approved for any use; only available inside registered clinical trials", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited under S0; erythropoietin derived)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Investigational drug that has completed phase 2 trials but is not approved by FDA or any other regulator as of the last verification date. Because cibinetide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded by 503A pharmacies or 503B outsourcing facilities. Products sold online as ARA-290 are unapproved drugs not lawful for human use.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is ARA-290 legal or FDA approved?", "a": "No. Cibinetide (ARA-290) is an investigational drug that has been through phase 2 trials but has no approval from FDA or any other regulator. It cannot be compounded because it is not a component of an approved product and is not on the 503A bulks list. The only lawful access is a registered clinical trial. Vials sold online are unapproved drugs not lawful for human use.", "source_ids": [ "fda-503a-bulks", "dahan-2014-review" ] }, { "q": "Does ARA-290 work for small fiber neuropathy?", "a": "Small trials say it helps. In 22 sarcoidosis patients, 4 weeks of ARA-290 improved the neuropathy symptom score by 11.5 points versus 2.9 on placebo. A 28 day subcutaneous trial improved symptoms and increased corneal nerve fiber density, and a 64 patient phase 2b trial found a significant increase in corneal nerve fiber area at 4 mg per day, consistent with actual nerve regrowth. The trials are short, small, and from a single sponsor, and no phase 3 has reported, so the evidence is promising rather than conclusive.", "source_ids": [ "heij-2012", "dahan-2013", "culver-2017" ] }, { "q": "What are the side effects of ARA-290?", "a": "In the 28 day trials no safety concerns emerged from clinical or laboratory monitoring, and by design it does not raise hemoglobin the way erythropoietin does. Injection site reactions are the main reported effect. Long term safety is unknown because no trial lasted more than a few weeks, and unregulated products sold online carry the added risks of unverified contents.", "source_ids": [ "heij-2012", "brines-2015" ] }, { "q": "How is ARA-290 taken and what doses were studied?", "a": "In trials it was a once daily subcutaneous injection of 1, 4, or 8 mg for 28 days, with 4 mg the most effective dose, or in the earliest pilot 2 mg intravenously three times a week for 4 weeks. No approved dosing exists outside these protocols, and the drug's plasma half life is only minutes despite a longer biological effect.", "source_ids": [ "culver-2017", "brines-2015", "heij-2012" ] }, { "q": "How much does ARA-290 cost?", "a": "It has no licensed price because it is not on the market; trial participants receive it free. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is ARA-290 banned by WADA?", "a": "Yes. Cibinetide has no approval from any government health authority, so it is prohibited at all times under section S0 (non-approved substances) of the WADA Prohibited List. Because it is derived from erythropoietin, athletes should also expect it to be treated under the S2 erythropoietin receptor agonist provisions.", "source_ids": [ "wada-list" ] }, { "q": "Does ARA-290 help diabetic neuropathy?", "a": "One small phase 2 trial suggests it might. In adults with type 2 diabetes and painful neuropathy, 28 days of 4 mg daily ARA-290 improved HbA1c and lipid profiles over 56 days of observation, improved PainDetect neuropathy scores, and increased corneal nerve fiber density in those with low baseline density. It is a single short study, not a basis for treatment.", "source_ids": [ "brines-2015" ] }, { "q": "ARA-290 vs BPC-157 for nerve repair: which has better evidence?", "a": "ARA-290, by a wide margin, even though neither is approved. ARA-290 has several placebo controlled human trials showing symptom improvement and measurable nerve fiber regrowth over 28 days. BPC-157 has only rodent data for nerve or tissue repair. The trade off is access: BPC-157 may be compounded in some states after the 2026 FDA advisory vote, while ARA-290 is available only in clinical trials.", "source_ids": [ "culver-2017", "dahan-2014-review" ] } ], "studies": [ { "pmid": "23168581", "title": "Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study", "year": 2012, "design": "Randomized, double blind, placebo controlled pilot trial, 4 weeks", "n": 22, "population": "Sarcoidosis patients with small fiber neuropathy symptoms and pain score 5 or more", "outcome": "Small fiber neuropathy screening list score improved minus 11.5 versus minus 2.9 with placebo; SF-36 pain and physical functioning improved; no safety concerns", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23168581/" }, { "pmid": "24136731", "title": "ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density", "year": 2013, "design": "Blinded, placebo controlled trial of 28 days of daily subcutaneous dosing", "population": "Sarcoidosis patients with documented small nerve fiber loss", "outcome": "Improved neuropathic symptoms, increased corneal small nerve fiber density, improved temperature sensitivity and 6 minute walk distance", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/24136731/" }, { "pmid": "28475703", "title": "Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain", "year": 2017, "design": "Randomized, placebo controlled phase 2b trial, 28 days", "n": 64, "population": "Sarcoidosis patients with small nerve fiber loss and neuropathic pain", "outcome": "Placebo corrected corneal nerve fiber area increased 697 square micrometers at 4 mg per day (P = 0.012); regenerating intraepidermal fibers increased", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/28475703/" }, { "pmid": "25387363", "title": "ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes", "year": 2015, "design": "Randomized, placebo controlled phase 2 trial, 28 days of dosing with 56 days of follow up", "population": "Adults with type 2 diabetes and painful neuropathy", "outcome": "Improved HbA1c and lipids, improved PainDetect neuropathy score, increased corneal nerve fiber density in those with low baseline density; no safety issues", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25387363/" } ], "sources": [ { "id": "heij-2012", "type": "pubmed", "title": "Heij L et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23168581/", "pmid": "23168581", "year": 2012 }, { "id": "dahan-2013", "type": "pubmed", "title": "Dahan A et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/24136731/", "pmid": "24136731", "year": 2013 }, { "id": "culver-2017", "type": "pubmed", "title": "Culver DA et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain. Invest Ophthalmol Vis Sci 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28475703/", "pmid": "28475703", "year": 2017 }, { "id": "brines-2015", "type": "pubmed", "title": "Brines M et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25387363/", "pmid": "25387363", "year": 2015 }, { "id": "dahan-2014-review", "type": "pubmed", "title": "Dahan A et al. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24555851/", "pmid": "24555851", "year": 2014 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, sections S0 non-approved substances and S2 peptide hormones", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "bpc-157", "tb-500", "thymosin-alpha-1", "kpv" ], "cluster": "healing", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "igf-1-lr3", "name": "IGF-1 LR3", "aliases": [ "Long R3 IGF-1", "Long [Arg3]-IGF-I", "LR3IGF-I", "LR3-IGF-1", "Long arginine 3 insulin-like growth factor 1" ], "class": "Recombinant 83 amino acid analog of human IGF-1 with a 13 amino acid N-terminal extension and arginine substituted for glutamate at position 3, engineered in 1992 to escape IGF binding proteins", "one_liner": "Lab research version of the growth factor IGF-1, 2 to 3 times more potent than IGF-1 in rats; no human study, not FDA approved, banned by WADA under S2.", "summary": "IGF-1 LR3 is an engineered version of insulin-like growth factor 1 (IGF-1, a growth factor the liver makes in response to growth hormone) designed for cell culture and animal research, with modifications that stop it binding to IGF binding proteins (blood proteins that normally hold IGF-1 in check) so more of it reaches the receptor. In rats it was about 2.5 times more anabolic (tissue building) than native IGF-1, but no human has received it in a published study, so its evidence grade is animal-only. It has never been reviewed by FDA, cannot be compounded (custom-made by a pharmacy), and IGF-1 and its analogs are prohibited by WADA under section S2, the anti-doping class for growth factors. The approved human IGF-1 product, mecasermin, is a different molecule with a narrow pediatric indication (a rare growth disorder in children).", "mechanism": "IGF-1 activates the IGF-1 receptor to stimulate protein synthesis, cell proliferation, and glucose uptake, and inhibits protein breakdown. In blood, most native IGF-1 is bound to IGF binding proteins, which limit its free concentration and half life. LR3 IGF-1 binds those proteins very poorly, so despite binding the IGF-1 receptor about 3 fold less well than IGF-1, it is more potent in vivo because more of it is free to act. It also binds the insulin receptor, which is one basis for its hypoglycemia risk.", "evidence_grade": "animal_only", "evidence_summary": "The evidence is 1990s in vitro and rat work from the group that engineered the analog. In rat myoblasts and hepatoma cells LR3 IGF-1 was more potent than IGF-1 at stimulating protein and DNA synthesis, and in dexamethasone treated catabolic rats it was about 2.5 fold more anabolic than IGF-1 on body weight and nitrogen retention, with increased gut weight. No human study of LR3 IGF-1 exists. Human data on IGF-1 itself come from mecasermin, the FDA approved recombinant IGF-1 for severe primary IGF-1 deficiency in children, whose label documents hypoglycemia, tonsillar hypertrophy, intracranial hypertension, and a contraindication in active or suspected cancer.", "human_evidence": "No indexed human study of IGF-1 LR3 identified. The nearest human evidence is the labeling for mecasermin (Increlex), a recombinant native IGF-1 approved in 2005 for children with severe primary IGF-1 deficiency, which lists hypoglycemia as the most common adverse reaction and contraindicates use in active or suspected malignancy; those findings concern a different, approved molecule and a pediatric population.", "animal_evidence": "In L6 rat myoblasts, Long [Arg3]-IGF-1 and other N-terminal analogs were more potent than IGF-1 at stimulating protein and DNA synthesis and inhibiting protein breakdown, with the greatest advantage in cells that secrete IGF binding proteins. In dexamethasone treated rats, LR3 IGF-1 and des(1-3) IGF-1 were about 2.5 fold more potent than IGF-1 at restoring body weight and nitrogen retention, decreased muscle protein breakdown, and increased gut weight by up to 45%, despite LR3 IGF-1 binding the type 1 IGF receptor 3 fold less well.", "conditions": [ "muscle-recovery" ], "literature_dosing": "Not established in human literature. Rat studies used continuous subcutaneous infusion by osmotic pump at microgram per day doses scaled to 150 g animals; these do not translate to a human dose. Mecasermin, the approved native IGF-1, is dosed in children at 0.04 to 0.12 mg/kg twice daily with meals under specialist supervision, and that regimen does not apply to LR3 IGF-1.", "routes": [ "Subcutaneous or intramuscular injection (as sold)", "Continuous subcutaneous infusion (rat studies)", "Cell culture reagent (its intended use)" ], "side_effects": [ "No human safety data for LR3 IGF-1", "Hypoglycemia, the most common adverse effect of IGF-1 (mecasermin label), expected to be more pronounced because LR3 escapes binding proteins", "Class effects documented for IGF-1: tonsillar hypertrophy, intracranial hypertension, slipped capital femoral epiphysis in children, injection site lipohypertrophy", "Theoretical promotion of tumor growth (IGF-1 signaling is mitogenic; mecasermin is contraindicated in cancer)", "Anecdotal reports of jaw and hand growth and organ enlargement with prolonged use (not documented in studies)" ], "interactions": [ "No formal human interaction studies exist", "Insulin and other glucose lowering drugs: additive hypoglycemia (IGF-1 class effect)", "Growth hormone and growth hormone secretagogues: additive IGF-1 axis activity (not studied)", "Corticosteroids blunt IGF-1 effects (animal data)" ], "contraindications": [ "Active or suspected cancer (mecasermin label contraindication applied by class)", "Closed epiphyses for growth promotion (mecasermin label)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Never submitted to or reviewed by FDA for human use. IGF-1 LR3 is not a component of an approved drug (mecasermin is native IGF-1, a different molecule), has no USP monograph, and has not been placed on the 503A bulks list, so it cannot lawfully be compounded by 503A pharmacies or 503B outsourcing facilities. It is sold as a cell culture reagent and research chemical, which is not lawful for human use.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product, not nominated for the 503A bulks list, and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "What is IGF-1 LR3?", "a": "IGF-1 LR3 (long arginine 3 IGF-1) is a lab-made version of insulin-like growth factor 1, a growth factor the body makes in response to growth hormone, with a 13 amino acid extension at one end and an arginine swapped in at position 3. Those changes reduce binding to IGF binding proteins (blood proteins that normally hold IGF-1 in check), and it was 2 to 3 times more anabolic (tissue building) than native IGF-1 in rats. It was built as a research reagent, a lab tool; no human study has been published, and it is not the approved IGF-1 drug mecasermin.", "source_ids": [ "francis-1992", "tomas-1992", "fda-increlex-label" ] }, { "q": "Is IGF-1 LR3 legal?", "a": "It is not an FDA approved drug and has never been reviewed by FDA. It cannot be compounded because it is not a component of an approved drug and is not on the 503A bulks list. The only products on the market are research reagents, which are not lawful for human use. Possession is not a crime, but no licensed channel can lawfully supply it for injection. The approved human IGF-1, mecasermin, is a different molecule restricted to children with severe IGF-1 deficiency.", "source_ids": [ "fda-503a-bulks", "fda-increlex-label" ] }, { "q": "Does IGF-1 LR3 build muscle?", "a": "In rats, it is strongly anabolic: about 2.5 times more potent than native IGF-1 at restoring body weight and nitrogen balance in a catabolic model, with reduced muscle protein breakdown. In humans nobody knows, because no study has ever given LR3 IGF-1 to people. The rat data also showed that it enlarged the gut by up to 45%, which hints at effects beyond skeletal muscle. PeptideAgent grades the evidence animal-only.", "source_ids": [ "tomas-1992", "francis-1992" ] }, { "q": "What are the side effects of IGF-1 LR3?", "a": "There are no human safety data for LR3 itself. The approved native IGF-1 (mecasermin) label lists hypoglycemia as the most common adverse effect, plus tonsillar enlargement, intracranial hypertension, and injection site fat growth, and it is contraindicated in cancer because IGF-1 signaling drives cell growth. LR3 is designed to have more free activity than IGF-1, so hypoglycemia is expected to be worse. Reports of jaw growth and organ enlargement with prolonged use are anecdotal.", "source_ids": [ "fda-increlex-label", "tomas-1992" ] }, { "q": "How much does IGF-1 LR3 cost?", "a": "There is no licensed source and therefore no legitimate price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is IGF-1 LR3 banned by WADA?", "a": "Yes. The WADA Prohibited List names insulin-like growth factor 1 (IGF-1) and its analogues under section S2 (peptide hormones, growth factors, related substances and mimetics), prohibited at all times. LR3 IGF-1 is an IGF-1 analog by definition.", "source_ids": [ "wada-list" ] }, { "q": "IGF-1 LR3 vs mecasermin (Increlex): what is the difference?", "a": "Mecasermin is native recombinant human IGF-1, FDA approved in 2005 for children with severe primary IGF-1 deficiency, dosed under specialist care with a known safety profile. IGF-1 LR3 is an engineered analog with an N-terminal extension and an arginine substitution that stop it binding IGF binding proteins, made for cell culture and never tested in humans. They are not interchangeable, and mecasermin's approval provides no legal cover for LR3.", "source_ids": [ "fda-increlex-label", "francis-1992" ] } ], "studies": [ { "pmid": "1378742", "title": "Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency", "year": 1992, "design": "In vitro cell culture (rat myoblasts, hepatoma cells, chicken fibroblasts) with receptor and binding protein assays", "population": "Cultured cell lines", "outcome": "Long [Arg3]-IGF-1 was more potent than IGF-1 at stimulating protein and DNA synthesis in cells that secrete IGF binding proteins, but less potent in cells that do not", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/1378742/" }, { "pmid": "1371669", "title": "Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats", "year": 1992, "design": "Rat catabolic model with continuous subcutaneous infusion for 7 days", "population": "Dexamethasone treated 150 g male rats", "outcome": "LR3 IGF-1 and des(1-3) IGF-1 were about 2.5 fold more potent than IGF-1 on body weight and nitrogen retention; muscle protein breakdown fell and gut weight rose up to 45%", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/1371669/" } ], "sources": [ { "id": "francis-1992", "type": "pubmed", "title": "Francis GL et al. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. J Mol Endocrinol 1992", "url": "https://pubmed.ncbi.nlm.nih.gov/1378742/", "pmid": "1378742", "year": 1992 }, { "id": "tomas-1992", "type": "pubmed", "title": "Tomas FM et al. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem J 1992", "url": "https://pubmed.ncbi.nlm.nih.gov/1371669/", "pmid": "1371669", "year": 1992 }, { "id": "fda-increlex-label", "type": "fda", "title": "FDA prescribing information for Increlex (mecasermin) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=increlex", "year": 2024 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (names IGF-1 and its analogues)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "peg-mgf", "follistatin-344", "mk-677", "cjc-1295" ], "cluster": "healing", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "IGF-1 LR3: evidence, risks, and legal status", "description": "IGF-1 LR3 is a lab reagent analog of IGF-1 with no human studies: what rat data show, expected risks, WADA status, and why it is not lawful.", "headings": { "safety": "IGF-1 LR3 risks and side effects" } } }, { "slug": "follistatin-344", "name": "Follistatin-344", "aliases": [ "FST-344", "FS344", "Follistatin 344", "FST", "Activin binding protein", "AAV1-FS344 (gene therapy form)" ], "class": "Recombinant form of the 344 amino acid precursor isoform of human follistatin, a secreted glycoprotein that binds and neutralizes myostatin, activins, and related TGF-beta family ligands", "one_liner": "Protein that blocks myostatin, the body's muscle growth brake: big gains in mice and monkeys; human data only from gene therapy, not injections; WADA banned.", "summary": "Follistatin-344 is a recombinant (lab-produced) version of the full length form of follistatin, a natural protein that binds myostatin and activin and so removes the main brake on skeletal muscle growth. Transgenic mice (bred to overproduce follistatin) roughly doubled to tripled muscle mass, and a single gene therapy injection (which delivers the follistatin gene so the body makes the protein) increased muscle size and strength in macaques, but the only human data come from small open label gene therapy trials (AAV1-FS344, with no placebo group) in muscular dystrophy and inclusion body myositis, both muscle wasting diseases, not from injecting the peptide. Injected follistatin-344 has no published human trial, is not FDA approved, is not on any FDA compounding list, and is prohibited at all times by WADA.", "mechanism": "Follistatin binds myostatin (GDF-8) and activin A and B with high affinity and blocks them from activating the activin type II receptors (ActRIIB and ActRIIA) on muscle cells. Loss of that signal reduces SMAD2/3 activity, releases satellite cells and protein synthesis from myostatin restraint, and produces both fiber hypertrophy and, during development, hyperplasia. The 344 isoform is the secreted precursor that is processed to the 315 (circulating) and 288 (tissue bound) forms; the 315 form is the one used in the AAV gene therapy trials because it binds heparan sulfate less and stays in the circulation. Follistatin also binds bone morphogenetic proteins and activins involved in reproduction and inflammation, which is the basis for concern about off target effects.", "evidence_grade": "animal_only", "evidence_summary": "Strong animal evidence that raising follistatin increases muscle mass: transgenic mice gained 194% to 327% in individual muscle weights, and a single intramuscular AAV1 gene therapy injection in cynomolgus macaques increased quadriceps size and strength for at least 15 months without measurable systemic toxicity. Human evidence is limited to two open label phase 1/2a gene therapy trials of 6 patients each (Becker muscular dystrophy and sporadic inclusion body myositis) that reported improved 6 minute walk distance without a placebo group. No published trial of injected recombinant follistatin-344 in humans was identified, so the evidence grade for the peptide as sold is animal-only. The human gene therapy trials used AAV1-FS344, not the injected peptide as sold; they are listed but do not raise the grade.", "human_evidence": "No indexed human trial of injected follistatin-344 peptide identified. The human data are for AAV1-FS344 gene therapy delivered into the quadriceps: in Becker muscular dystrophy (n = 6, 2015) 4 of 6 patients improved 6 minute walk distance by 58 to 125 meters over 1 year with no serious adverse events; in sporadic inclusion body myositis (n = 6, 2017) treated patients improved 6 minute walk distance by a mean of 56 meters at 1 year while untreated comparators declined. Both trials were open label, unblinded, and too small to establish efficacy; the therapy has not advanced to approval.", "animal_evidence": "Lee and McPherron (2001) showed that transgenic mice overexpressing follistatin had muscle weights 194% to 327% above wild type, exceeding the gain seen in myostatin knockout mice, which implicated additional ligands beyond myostatin. Kota et al. (2009) gave a single bilateral quadriceps injection of AAV1-FS344 to cynomolgus macaques and measured increased muscle circumference, fiber size, and strength persisting 15 months, with normal reproductive hormones and organ histology. Rodent models of muscular dystrophy and cachexia treated with follistatin gene delivery or recombinant follistatin also show increased muscle mass and strength.", "conditions": [ "muscle-recovery" ], "literature_dosing": "Not established in human literature for the injected peptide. The only human dosing data are for AAV1-FS344 gene therapy, given as a single intramuscular series of 6 x 10^11 to 1.2 x 10^12 vector genomes per kg into the quadriceps, which does not translate to any peptide dose. Products sold as follistatin-344 for injection have no dose finding data of any kind.", "routes": [ "Subcutaneous or intramuscular injection (as sold, no human data)", "Intramuscular AAV1 gene therapy (clinical trials only)", "Transgenic overexpression and intramuscular viral vector (animal studies)" ], "side_effects": [ "No human safety data for injected follistatin-344", "Follistatin binds activins that regulate FSH release, so suppression of fertility hormones is a theoretical concern (not seen in the 15 month macaque study)", "Activin and follistatin regulate wound healing, inflammation, and liver regeneration, so off target effects are plausible and untested", "Products sold as research chemicals are unverified for identity, purity, and endotoxin" ], "interactions": [ "No human interaction studies exist", "Theoretical additive muscle growth and hormonal effects when combined with other myostatin pathway agents, growth hormone secretagogues, or IGF-1 analogs; none tested" ], "contraindications": [ "Competitive athletes subject to WADA testing (prohibited at all times as a myostatin inhibitor)", "Pregnancy, planned conception, and breastfeeding (activin signaling is essential for reproduction; no data)", "Active cancer (activin and follistatin signaling affect tumor growth in both directions; no data)", "Anyone: no lawful human product exists" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Follistatin-344 has never been submitted to or reviewed by FDA as a drug and does not appear on the 503A bulk drug substance Category 1, 2, or 3 lists or the 503B bulks list as of the last verification date. It is a biologic sized protein rather than a small peptide, so even a nomination would face the biologics compounding limits. There is no approved product and no lawful compounding pathway; products sold online are labeled for research use only.", "typical_cost": "Not available through licensed channels. Research chemical listings for 1 mg vials are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available for human use in the United States.", "Gene therapy form (AAV1-FS344) was available only inside registered clinical trials.", "Products labeled research use only are not lawful for human use and are not verified." ], "faqs": [ { "q": "Is follistatin-344 legal in the United States?", "a": "It is not an FDA approved drug, it is not on any FDA compounding bulks list (the lists of raw ingredients pharmacies may use to custom-make drugs), and there is no lawful way to obtain it for human use. Possessing it is not itself a crime, but selling it for human use is unlawful, and products labeled research use only are not tested for identity or purity. The only human exposure to follistatin has been inside registered gene therapy trials, which deliver the follistatin gene rather than the protein.", "source_ids": [ "fda-503a-bulks", "mendell-2015" ] }, { "q": "Does follistatin-344 build muscle in humans?", "a": "Unknown. The dramatic muscle gains come from mice (194% to 327% larger muscles when follistatin was overexpressed) and macaques (larger, stronger quadriceps for 15 months after a gene therapy injection). In people, two open label gene therapy trials of 6 patients each reported better 6 minute walk distances in muscular dystrophy and inclusion body myositis, but there was no placebo group and no muscle mass endpoint that would settle the question. Injected follistatin-344 peptide has never been tested in a published human trial.", "source_ids": [ "lee-2001", "kota-2009", "mendell-2015", "mendell-2017" ] }, { "q": "What are the side effects of follistatin-344?", "a": "There is no human safety data for the injected peptide. The concerns are mechanistic: follistatin also neutralizes activins, which control FSH release and fertility, wound healing, inflammation, and liver regeneration. The 15 month macaque gene therapy study found no change in reproductive hormones or organ histology, and the two small human gene therapy trials reported no serious adverse events, but those were local muscle injections of a vector, not systemic peptide. Unverified research chemical products add contamination and endotoxin risk.", "source_ids": [ "kota-2009", "mendell-2015", "mendell-2017" ] }, { "q": "How is follistatin-344 taken?", "a": "In the only human studies it was not injected as a peptide at all: patients received a one time series of AAV1 vector injections into the quadriceps that made muscle cells produce follistatin. Products sold as follistatin-344 are lyophilized protein for subcutaneous or intramuscular injection, and no human dose finding, pharmacokinetic, or safety study exists for that route. A 344 amino acid glycoprotein is also large and fragile enough that purity and folding of unregulated products is a real question.", "source_ids": [ "mendell-2015", "kota-2009" ] }, { "q": "How much does follistatin-344 cost?", "a": "There is no licensed product and no compounding pathway, so there is no legitimate price. Research chemical sellers list 1 mg vials, but those products are not lawful for human use and are not verified for identity, purity, or biological activity, which for a folded 344 amino acid protein is not guaranteed. PeptideAgent does not track gray market pricing.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is follistatin-344 banned by WADA?", "a": "Yes. The WADA Prohibited List names follistatin explicitly under section S4 (hormone and metabolic modulators) as a myostatin binding protein among agents preventing activin receptor IIB activation. It is prohibited at all times, in and out of competition, for every athlete subject to the Code.", "source_ids": [ "wada-list" ] }, { "q": "Follistatin-344 vs ACE-031: what is the difference?", "a": "Both block the myostatin and activin pathway but from different sides. Follistatin is the natural binding protein that soaks up myostatin and activins; ACE-031 is a soluble copy of the receptor (ActRIIB) fused to an antibody fragment that does the same job. ACE-031 has published placebo controlled human trials and known bleeding and vascular side effects that halted its development; follistatin has only animal data and open label gene therapy pilots. Neither is approved or lawfully available, and both are WADA prohibited.", "source_ids": [ "lee-2001", "mendell-2017", "wada-list" ] }, { "q": "Is follistatin gene therapy the same as injecting follistatin-344?", "a": "No. The gene therapy trials injected an AAV1 vector carrying the FS344 gene into thigh muscle so the muscle would produce the 315 isoform of follistatin locally for years. Injecting the protein itself gives a short lived systemic exposure with a different distribution, and there is no human evidence that it produces any of the effects seen with gene delivery. Marketing that cites the gene therapy trials to sell injectable peptide is comparing two different things.", "source_ids": [ "mendell-2015", "kota-2009" ] } ], "studies": [ { "pmid": "11459935", "title": "Regulation of myostatin activity and muscle growth", "year": 2001, "design": "Transgenic mouse study", "population": "Mice overexpressing follistatin, myostatin propeptide, or dominant negative ActRIIB in skeletal muscle", "outcome": "Follistatin transgenic mice had individual muscle weights 194% to 327% above wild type, exceeding myostatin knockout, implying follistatin blocks additional growth inhibiting ligands", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/11459935/" }, { "pmid": "20368179", "title": "Follistatin gene delivery enhances muscle growth and strength in nonhuman primates", "year": 2009, "design": "Nonhuman primate gene therapy study with 15 month follow up", "population": "Cynomolgus macaques given bilateral quadriceps injections of AAV1-FS344", "outcome": "Increased muscle size, fiber diameter, and strength maintained for 15 months with no change in reproductive hormones or organ histology", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/20368179/" }, { "pmid": "25322757", "title": "A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy", "year": 2015, "design": "Open label, dose escalation phase 1/2a gene therapy trial, 1 year follow up", "n": 6, "population": "Ambulatory adult men with Becker muscular dystrophy", "outcome": "4 of 6 patients improved 6 minute walk distance by 58 to 125 meters; no serious adverse events; no placebo group", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/25322757/" }, { "pmid": "28279643", "title": "Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes", "year": 2017, "design": "Open label phase 1/2a gene therapy trial with untreated comparator group, 1 year follow up", "n": 6, "population": "Adults with sporadic inclusion body myositis", "outcome": "Treated patients improved 6 minute walk distance by a mean 56 meters at 1 year while untreated comparators declined; unblinded, small sample", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/28279643/" } ], "sources": [ { "id": "lee-2001", "type": "pubmed", "title": "Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11459935/", "pmid": "11459935", "year": 2001 }, { "id": "kota-2009", "type": "pubmed", "title": "Kota J et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/20368179/", "pmid": "20368179", "year": 2009 }, { "id": "mendell-2015", "type": "pubmed", "title": "Mendell JR et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Mol Ther 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25322757/", "pmid": "25322757", "year": 2015 }, { "id": "mendell-2017", "type": "pubmed", "title": "Mendell JR et al. Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Mol Ther 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28279643/", "pmid": "28279643", "year": 2017 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S4 hormone and metabolic modulators (names follistatin as a myostatin binding protein)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ace-031", "peg-mgf", "igf-1-lr3", "mk-677" ], "cluster": "healing", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "ace-031", "name": "ACE-031 (ramatercept)", "aliases": [ "Ramatercept", "ActRIIB-IgG1", "Soluble activin receptor type IIB", "ACE 031" ], "class": "Recombinant fusion protein (extracellular domain of activin receptor type IIB fused to human IgG1 Fc), a myostatin and activin ligand trap", "one_liner": "A myostatin blocking fusion protein that grew lean mass in a small human trial but was abandoned after bleeding side effects in boys with DMD.", "summary": "ACE-031 (ramatercept) is a recombinant decoy receptor that binds myostatin and related ligands so they cannot signal muscle to stop growing. In a 48 person single dose trial it increased lean mass and thigh muscle volume within a month, but a randomized trial in boys with Duchenne muscular dystrophy was stopped early because of nosebleeds, dilated skin vessels, and no significant walking benefit, and development ended in 2011. It was never approved by any regulator, is prohibited by WADA at all times, and is not available through any lawful channel.", "mechanism": "ACE-031 is the extracellular part of activin receptor type IIB (ActRIIB) fused to an antibody Fc fragment. Circulating in the blood, it soaks up myostatin, activin A, GDF-11, and other TGF-beta family ligands before they can bind ActRIIB on muscle cells. Blocking that signal releases the brake on muscle protein synthesis and satellite cell activity. Because ActRIIB ligands also act on blood vessels, bone, and red blood cell production, the same trap produced vascular and hematologic side effects in trials.", "evidence_grade": "human_rct", "evidence_summary": "Two published human trials. A single ascending dose study in 48 healthy postmenopausal women (2013) showed dose dependent increases in total body lean mass (about 3% at the highest dose after 29 days), thigh muscle volume, and bone formation markers, with a drop in fat mass. A randomized placebo controlled trial in ambulatory boys with Duchenne muscular dystrophy (published 2017) was halted after 24 participants because of epistaxis, telangiectasia, and gum bleeding; lean mass rose but the 6 minute walk distance did not improve significantly. No trial has tested it in adults for performance or aging, and the program was discontinued.", "human_evidence": "Attie et al. 2013: 48 healthy postmenopausal women received a single subcutaneous dose of ACE-031 (0.02 to 3 mg/kg) or placebo. At 1 mg/kg and above, total body lean mass increased by roughly 1 kg and thigh muscle volume by about 5% at day 29; fat mass and leptin fell and bone specific alkaline phosphatase rose. Campbell et al. 2017: 24 ambulatory boys with Duchenne muscular dystrophy were randomized to ACE-031 (0.5 or 1 mg/kg every 2 to 4 weeks) or placebo for 12 weeks. Lean mass and bone density increased, 6 minute walk distance showed a nonsignificant trend, and the trial was stopped early for nosebleeds, telangiectasia, and erythema.", "animal_evidence": "In mice, soluble ActRIIB decoy receptors produce rapid, large increases in skeletal muscle mass (often 30% to 60% within two weeks) across many muscle groups and in models of muscular dystrophy, cancer cachexia, and disuse. Bone mass also increases. These preclinical effects motivated the human program and are summarized in the 2013 human trial report.", "conditions": [ "muscle-recovery" ], "literature_dosing": "Human trials used single subcutaneous doses of 0.02 to 3 mg/kg in healthy women (Attie 2013) and 0.5 or 1 mg/kg subcutaneously every 2 to 4 weeks for 12 weeks in boys with Duchenne muscular dystrophy (Campbell 2017). Development stopped after these trials, so no dose was ever established for any indication.", "routes": [ "Subcutaneous injection (clinical trials)" ], "side_effects": [ "Nosebleeds (epistaxis), reported in most treated boys in the DMD trial", "Telangiectasia (dilated small skin vessels) and gum bleeding", "Skin erythema and injection site reactions", "Rise in hemoglobin and hematocrit (ActRIIB ligands regulate red cell production)", "Decrease in serum FSH observed in the single dose study", "Long term safety unknown; program discontinued in 2011" ], "interactions": [ "No formal interaction studies exist", "Theoretical additive bleeding or vascular risk with anticoagulants and antiplatelet drugs, based on the telangiectasia and epistaxis seen in trials", "Theoretical additive erythrocytosis with erythropoiesis stimulating agents or testosterone" ], "contraindications": [ "Any use outside a clinical trial; no approved indication exists", "Bleeding disorders or hereditary hemorrhagic telangiectasia (based on trial adverse events)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (myostatin inhibitors are prohibited at all times)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "ACE-031 is an investigational biologic that was never submitted for FDA approval; its sponsor ended development in 2011 after the Duchenne trial was halted. It is not on the FDA 503A bulks list, has not been nominated or reviewed by the Pharmacy Compounding Advisory Committee, and as a recombinant fusion protein it is not a candidate for 503A compounding. Products sold under this name are not lawful for human use and their identity cannot be verified.", "typical_cost": "Not available through licensed channels. Research chemical listings for material labeled ACE-031 exist, but the products are unverified and are not lawful for human use.", "access_path": [ "Not legally available: no approved product, no active clinical trials, and not eligible for compounding.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is ACE-031 legal or FDA approved?", "a": "No. ACE-031 was an investigational drug studied in a single dose trial in healthy volunteers and one randomized trial in boys with Duchenne muscular dystrophy. Development stopped in 2011 and it was never approved anywhere. It is not eligible for compounding and there is no lawful way to obtain it for human use in the United States.", "source_ids": [ "campbell-2017", "fda-503a-bulks" ] }, { "q": "Does ACE-031 build muscle in humans?", "a": "In the only healthy volunteer trial, a single dose of 1 mg/kg or more increased total lean mass by about 1 kg and thigh muscle volume by about 5% within 29 days in 48 postmenopausal women. In boys with Duchenne muscular dystrophy, lean mass also rose over 12 weeks, but walking distance did not improve significantly and the trial was stopped for safety. No study has tested it for strength or performance in healthy adults.", "source_ids": [ "attie-2013", "campbell-2017" ] }, { "q": "What are the side effects of ACE-031?", "a": "The Duchenne trial was halted because of nosebleeds, telangiectasia (dilated skin blood vessels), gum bleeding, and skin redness. Hemoglobin also rose, which is expected because the same receptor pathway regulates red blood cell production. Long term safety was never studied because the program ended.", "source_ids": [ "campbell-2017", "attie-2013" ] }, { "q": "How was ACE-031 taken in trials?", "a": "By subcutaneous injection. Healthy volunteers received a single dose of 0.02 to 3 mg/kg. Boys with Duchenne muscular dystrophy received 0.5 or 1 mg/kg every 2 to 4 weeks for 12 weeks. No maintenance regimen was ever defined because development stopped.", "source_ids": [ "attie-2013", "campbell-2017" ] }, { "q": "Is ACE-031 banned by WADA?", "a": "Yes. Myostatin inhibitors, including agents that reduce or block myostatin signaling such as ActRIIB decoy receptors, are listed under section S4 of the WADA Prohibited List and are prohibited at all times, in and out of competition.", "source_ids": [ "wada-list" ] }, { "q": "How much does ACE-031 cost?", "a": "There is no lawful price because it is not sold through any licensed channel. Listings on research chemical sites cannot be verified as genuine ACE-031, which is a complex recombinant protein that is difficult to manufacture, and those products are not lawful for human use.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "ACE-031 vs follistatin: what is the difference?", "a": "Both block myostatin, but by different means. ACE-031 is a soluble copy of the myostatin receptor (ActRIIB) fused to an antibody fragment, so it traps myostatin, activins, and GDF-11 in the blood. Follistatin is a natural binding protein for the same ligands. ACE-031 has two published human trials and known vascular side effects; follistatin-344 has no published human trial data. Neither is approved or lawfully available.", "source_ids": [ "attie-2013", "campbell-2017" ] } ], "studies": [ { "pmid": "23169607", "title": "A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers", "year": 2013, "design": "Randomized, double blind, placebo controlled single ascending dose trial", "n": 48, "population": "Healthy postmenopausal women", "outcome": "Dose dependent increases in total lean mass and thigh muscle volume at day 29 at 1 mg/kg and above; decreased fat mass and leptin; increased bone formation markers", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23169607/" }, { "pmid": "27462804", "title": "Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial", "year": 2017, "design": "Randomized, double blind, placebo controlled trial, 12 weeks, stopped early", "n": 24, "population": "Ambulatory boys with Duchenne muscular dystrophy", "outcome": "Increased lean mass and bone mineral density; nonsignificant trend in 6 minute walk distance; trial halted for epistaxis, telangiectasia, and erythema", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27462804/" } ], "sources": [ { "id": "attie-2013", "type": "pubmed", "title": "Attie KM et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23169607/", "pmid": "23169607", "year": 2013 }, { "id": "campbell-2017", "type": "pubmed", "title": "Campbell C et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle Nerve 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/27462804/", "pmid": "27462804", "year": 2017 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S4 (hormone and metabolic modulators, including myostatin inhibitors)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "follistatin-344", "igf-1-lr3", "peg-mgf" ], "cluster": "healing", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "epitalon", "name": "Epitalon", "aliases": [ "Epithalon", "Epithalone", "Ala-Glu-Asp-Gly", "AEDG peptide", "Epithalamin (pineal extract it was derived from)", "Epitalon peptide", "Epithalon peptide", "Epitalone" ], "class": "Synthetic tetrapeptide (Ala-Glu-Asp-Gly) modeled on the bovine pineal extract Epithalamin", "one_liner": "4 amino acid peptide from a pineal gland extract: telomere and lifespan data in cells and mice, small non-randomized Russian human reports, not FDA approved.", "summary": "Epitalon is a four amino acid synthetic peptide developed in St. Petersburg as a defined version of Epithalamin, an extract of the pineal gland (a small hormone gland in the brain). In cultured human cells it activates telomerase, the enzyme that rebuilds telomeres (the protective caps on chromosome ends), and lengthens telomeres, and in mice it modestly extended life span and reduced spontaneous tumors, but the only human data are small, non-randomized reports (no chance assignment to a comparison group) from the group that invented it. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and its advisory committee recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but no final rule has been published.", "mechanism": "In human fibroblast and other cell lines, epitalon induces expression of the telomerase catalytic subunit (hTERT), increases telomerase activity, and lengthens telomeres; a 2025 study found telomere elongation through telomerase upregulation or the alternative lengthening pathway depending on the cell line. The developers also propose that it binds DNA and regulates gene expression epigenetically and that it normalizes melatonin rhythms through the pineal gland. These mechanisms are documented in cell culture and rodents and have not been confirmed in humans.", "evidence_grade": "animal_only", "evidence_summary": "Cell culture studies show telomerase activation and telomere elongation in human somatic cells. In female SHR mice given epitalon monthly for life, mean life span of the last 10% of survivors increased and spontaneous tumor incidence fell, while overall mean life span did not change significantly. Human data consist of open, non-randomized reports from the developer's institute in elderly patients, mostly using the pineal extract Epithalamin rather than the synthetic peptide, with reported reductions in mortality and cardiovascular events over 6 to 12 years. No independent randomized human trial has been published, so the grade is animal-only. The human observational reports are non-randomized institutional series, mostly of the pineal extract rather than the synthetic peptide; they are listed but do not raise the grade.", "human_evidence": "No independent randomized controlled trial identified. Khavinson and Morozov (2003) reported that elderly patients treated with pineal peptide preparations (Epithalamin, with Thymalin) in open, non-randomized follow up over 6 to 12 years had lower mortality and fewer cardiovascular and respiratory events than untreated controls; this work comes from the developing institute and used the extract rather than synthetic epitalon in most arms. Cell studies used human fibroblasts and other human cell lines, not people.", "animal_evidence": "Anisimov et al. (2003) gave female Swiss-derived SHR mice epitalon 0.1 ug subcutaneously five times a week, monthly courses, from age 3 months until death: the peptide slowed some aging biomarkers, increased the life span of the longest lived 10% of mice, and reduced spontaneous tumor incidence, but did not significantly change mean life span. Rat studies from the same group report protective effects against light-induced pineal aging and retinal changes.", "conditions": [ "longevity", "sleep", "skin-aging" ], "literature_dosing": "Not established in human literature. Mouse life span studies used 0.1 ug per mouse subcutaneously in monthly 5 day courses. Human reports from the developer's institute describe 10 mg intramuscular courses of the related extract Epithalamin, not a dose finding study of epitalon. No human pharmacokinetic or dose ranging study has been published.", "routes": [ "Subcutaneous injection (as sold)", "Intramuscular injection (Russian Epithalamin reports)", "Intranasal and oral products exist without absorption data" ], "side_effects": [ "No systematic human safety data published", "Injection site reactions reported anecdotally", "Theoretical concern that telomerase activation could support growth of existing tumors, although mouse studies reported fewer spontaneous tumors", "Effects on melatonin rhythm are proposed and could alter sleep timing" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive effects with melatonin or sedatives given proposed pineal effects (not tested)" ], "contraindications": [ "Active cancer or history of cancer (theoretical telomerase concern, untested in humans)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "under_review", "compounding_status": "Epitalon was placed on the FDA 503A Category 2 list (substances with significant safety risks) in 2023 and removed from it on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding epitalon to the 503A bulks list. As of the last verification date FDA has not published a final rule, so compounding pharmacies and state boards vary in whether they will fill it. It is not an FDA approved drug and is not eligible for 503B outsourcing.", "typical_cost": "No lawful compounded price: Epitalon is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is epitalon peptide, and is epithalon the same thing?", "a": "Yes, they are the same. Epitalon, epithalon, and epithalone are spellings of one synthetic four amino acid peptide, Ala-Glu-Asp-Gly (AEDG). It was made in St. Petersburg as a defined version of Epithalamin, an extract of bovine (cow) pineal gland, a small hormone gland in the brain, and is marketed for longevity. It is not FDA approved; the FDA advisory committee recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but no final rule has been published.", "source_ids": [ "araj-2025", "fda-pcac-2026" ] }, { "q": "Is epitalon legal in the United States?", "a": "It is not an FDA approved drug, but possessing it is not a crime. FDA removed epitalon from its 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee voted in July 2026 to recommend it for the 503A bulks list. Until FDA publishes a final rule it is not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. Research chemical products are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Epitalon benefits: what does the evidence show?", "a": "The claimed benefits come from cell and animal work. In cultured human cells it switched on telomerase and lengthened telomeres. In female mice given monthly courses for life, the longest lived tenth lived longer and fewer spontaneous tumors developed, although average life span did not change. Cell and rodent studies also report effects on melatonin production. In people, the only reports are small non-randomized series from the developing institute, mostly of the pineal extract rather than epitalon, so human benefits are unproven. PeptideAgent grades the evidence animal-only.", "source_ids": [ "khavinson-2003-telomerase", "anisimov-2003", "araj-2025", "khavinson-2003-human" ] }, { "q": "Does epitalon actually lengthen telomeres or extend life?", "a": "In cultured human cells, yes: epitalon increased telomerase activity and telomere length in a 2003 study and again in a 2025 study across several cell lines. In mice, monthly courses increased the life span of the longest lived 10% and reduced tumors but did not change mean life span. No human study has measured telomere length or life span after epitalon, so the human claim is untested.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025", "anisimov-2003" ] }, { "q": "How does epitalon work?", "a": "The proposed mechanisms come from cell and animal studies. Epitalon increases expression and activity of telomerase, the enzyme that rebuilds the protective ends of chromosomes, and a 2025 study found telomere lengthening in several human cell lines through telomerase or an alternative pathway. A 2025 review also summarizes effects on melatonin synthesis, antioxidant enzymes, and gene expression. None of this has been measured in people, and no human pharmacokinetic study has been published, so its half-life in people is unknown.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025", "araj-2025" ] }, { "q": "What are the side effects of epitalon?", "a": "No systematic human safety study exists. Anecdotal reports mention injection site irritation. The main theoretical concern is that a telomerase activator could help existing cancer cells keep dividing, though treated mice actually developed fewer spontaneous tumors. That question has never been studied in people.", "source_ids": [ "anisimov-2003", "khavinson-2003-telomerase" ] }, { "q": "How is epitalon taken?", "a": "In mouse studies it was injected subcutaneously in monthly 5 day courses. Russian human reports used intramuscular courses of the related pineal extract Epithalamin. Products sold to people are usually injection vials, with some intranasal and oral versions that have no absorption data. There is no human dose finding study.", "source_ids": [ "anisimov-2003", "khavinson-2003-human" ] }, { "q": "How much does epitalon cost?", "a": "There is no lawful compounded price: it is not on the 503A bulks list, and advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is epitalon banned by WADA?", "a": "Yes. Epitalon has no current approval from any government health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "Epitalon vs thymalin: what is the difference?", "a": "Both come from the same St. Petersburg institute. Epitalon is a defined 4 amino acid synthetic peptide modeled on the pineal extract Epithalamin; thymalin is a thymus extract used as an immune modulator. The 2003 human report that is often cited for epitalon actually studied Epithalamin and Thymalin together in elderly patients without randomization. Neither has an independent randomized trial or FDA approval.", "source_ids": [ "khavinson-2003-human" ] } ], "studies": [ { "pmid": "12937682", "title": "Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells", "year": 2003, "design": "In vitro study of human fetal fibroblast cultures", "population": "Human somatic cell cultures", "outcome": "Epitalon induced telomerase catalytic subunit expression, increased telomerase activity, and lengthened telomeres in cultured cells", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/12937682/" }, { "pmid": "14501183", "title": "Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice", "year": 2003, "design": "Lifelong controlled mouse study, monthly subcutaneous courses from 3 months of age", "population": "Female Swiss-derived SHR mice", "outcome": "Slowed several aging biomarkers, increased life span of the last 10% of survivors, and reduced spontaneous tumor incidence; mean life span not significantly changed", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/14501183/" }, { "pmid": "14523363", "title": "Peptides of pineal gland and thymus prolong human life", "year": 2003, "design": "Open, non-randomized long term follow up of elderly patients treated with pineal and thymus peptide preparations", "population": "Elderly patients in Russia treated with Epithalamin and Thymalin", "outcome": "Authors report lower mortality and fewer cardiovascular and respiratory events over 6 to 12 years versus untreated controls; not randomized and from the developing institute", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/14523363/" }, { "pmid": "40908429", "title": "Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity", "year": 2025, "design": "In vitro study of multiple human cell lines", "population": "Human cell lines", "outcome": "Telomere elongation via telomerase upregulation in some lines and alternative lengthening of telomeres in others", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/40908429/" } ], "sources": [ { "id": "khavinson-2003-telomerase", "type": "pubmed", "title": "Khavinson VK, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12937682/", "pmid": "12937682", "year": 2003 }, { "id": "anisimov-2003", "type": "pubmed", "title": "Anisimov VN et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/14501183/", "pmid": "14501183", "year": 2003 }, { "id": "khavinson-2003-human", "type": "pubmed", "title": "Khavinson VK, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/14523363/", "pmid": "14523363", "year": 2003 }, { "id": "al-dulaimi-2025", "type": "pubmed", "title": "Al-Dulaimi S et al. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40908429/", "pmid": "40908429", "year": 2025 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "araj-2025", "type": "pubmed", "title": "Araj SK et al. Overview of Epitalon, highly bioactive pineal tetrapeptide with promising properties. Int J Mol Sci 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40141333/", "pmid": "40141333", "year": 2025 } ], "related": [ "thymalin", "mots-c", "pinealon", "dsip" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Epitalon (epithalon) peptide: benefits and legal status", "description": "Epitalon, also spelled epithalon: what telomere and mouse life span studies show, side effects, how it works, and its 2026 FDA status.", "h1": "Epitalon (epithalon) peptide", "headings": { "evidence": "Epitalon benefits: what the evidence shows", "safety": "Epitalon side effects" } } }, { "slug": "mots-c", "name": "MOTS-c", "aliases": [ "Mitochondrial open reading frame of the 12S rRNA type-c", "MOTS c", "Mitochondrial derived peptide MOTS-c", "MOTS-c peptide", "MOTSc", "MOTS c peptide" ], "class": "Mitochondrial derived peptide (16 amino acids) encoded in the 12S rRNA region of mitochondrial DNA", "one_liner": "A 16 amino acid peptide coded by mitochondrial DNA that improves metabolism and exercise capacity in mice; human data limited to blood levels and genetics.", "summary": "MOTS-c is a 16 amino acid peptide encoded by mitochondrial DNA (the separate genetic code inside the cell's energy-producing mitochondria) that acts as a metabolic signal. In mice it activates AMPK, the cell's energy sensor, prevents diet induced obesity and insulin resistance, and improves exercise capacity and physical decline with age, but human evidence is limited to circulating levels that rise with exercise and a genetic variant linked to diabetes risk, with no published human treatment trial. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026; no final rule has been published.", "mechanism": "MOTS-c is translated from a short open reading frame inside the mitochondrial 12S rRNA gene. In cells and mice it inhibits the folate cycle and de novo purine synthesis, which raises AICAR and activates AMPK, increasing glucose uptake and fatty acid oxidation in skeletal muscle. Under metabolic stress it moves into the nucleus and regulates stress response genes. Circulating levels in people rise acutely with exercise and fall with age. All mechanistic work is in cells and rodents.", "evidence_grade": "animal_only", "evidence_summary": "The foundational 2015 mouse study showed that MOTS-c injection prevented high fat diet induced obesity and insulin resistance and improved glucose handling in aged mice. A 2021 study showed that circulating MOTS-c rises with exercise in young men and that treating mice, including old mice, improved running capacity and physical performance. Human data are observational: an East Asian mitochondrial DNA variant that changes the MOTS-c sequence is associated with type 2 diabetes in men. No human interventional trial of MOTS-c has been published, and a phase 1 study of a related analog by a former sponsor was never published in a peer reviewed journal. The human study is a genetic association study, not an intervention with the peptide; it is listed but does not raise the grade.", "human_evidence": "No indexed human treatment trial identified. Reynolds et al. 2021 measured MOTS-c in skeletal muscle and plasma of 10 healthy young men before and after exercise and found it rose acutely. Zempo et al. 2021 reported that the m.1382A>C mitochondrial DNA variant, which substitutes lysine 14 with glutamine in MOTS-c, was associated with type 2 diabetes in Japanese men and reduced the peptide's metabolic activity in cells. These are correlational findings, not treatment effects.", "animal_evidence": "Lee et al. 2015: daily intraperitoneal MOTS-c (0.5 mg/kg) prevented weight gain and insulin resistance in mice on a high fat diet and improved insulin sensitivity in aged mice, working through AMPK activation in skeletal muscle. Reynolds et al. 2021: MOTS-c treatment (15 mg/kg) improved treadmill running in young, middle aged, and old mice, and late life treatment improved physical capacity and some healthspan measures.", "conditions": [ "longevity", "obesity", "type-2-diabetes" ], "literature_dosing": "Not established in human literature. Mouse studies used 0.5 mg/kg per day intraperitoneally (metabolic studies) and up to 15 mg/kg (exercise studies). No human dose finding or pharmacokinetic study has been published.", "routes": [ "Subcutaneous injection (as sold)", "Intraperitoneal injection (animal studies)" ], "side_effects": [ "No systematic human safety data published", "Injection site reactions reported anecdotally", "Theoretical risk of hypoglycemia given AMPK activation and improved glucose uptake in mice (not demonstrated in humans)" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive glucose lowering with insulin, sulfonylureas, metformin, or GLP-1 agonists, based on mouse AMPK data (not tested)" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "History of hypoglycemia or insulin treated diabetes without medical supervision (theoretical)", "Competitive athletes subject to WADA testing (prohibited at all times under S4.4)" ], "wada_status": "prohibited", "fda_status": "under_review", "compounding_status": "MOTS-c was placed on the FDA 503A Category 2 list (substances with significant safety risks) in 2023 and removed from it on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding MOTS-c to the 503A bulks list. As of the last verification date FDA has not published a final rule, so compounding pharmacies and state boards vary in whether they will fill it. It is not an FDA approved drug and is not eligible for 503B outsourcing.", "typical_cost": "No lawful compounded price: MOTS-c is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is MOTS-c peptide?", "a": "MOTS-c is a 16 amino acid peptide encoded by mitochondrial DNA, the separate genes inside the cell's energy-producing mitochondria, rather than the cell nucleus. It acts as a metabolic signal: in mice it activates AMPK, the cell's energy sensor, improves insulin sensitivity (how well the body responds to insulin), and rises with exercise. It is marketed for weight loss, energy, and healthy aging, but no human treatment trial has been published. It is not FDA approved; the FDA advisory committee recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026, but no final rule has been published.", "source_ids": [ "lee-2015", "reynolds-2021", "fda-pcac-2026" ] }, { "q": "Is MOTS-c legal in the United States?", "a": "It is not an FDA approved drug, but possessing it is not a crime. FDA removed MOTS-c from its 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee voted in July 2026 to recommend it for the 503A bulks list. Until FDA publishes a final rule it is not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. Research chemical products are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "MOTS-c benefits: what does the evidence show?", "a": "The benefit claims come from mice. MOTS-c injections prevented diet induced obesity and insulin resistance, improved glucose handling in older mice, and improved running capacity and physical function in young, middle aged, and old mice. In people, the evidence is only that blood and muscle levels rise with exercise and that a genetic variant in the MOTS-c sequence is linked to diabetes risk. PeptideAgent grades the evidence animal-only.", "source_ids": [ "lee-2015", "reynolds-2021", "zempo-2021" ] }, { "q": "Does MOTS-c work for weight loss or insulin resistance?", "a": "In mice, yes: daily injections prevented diet induced obesity and insulin resistance and improved glucose handling in old mice. In humans, nobody knows, because no treatment trial has been published. The human evidence is that blood levels rise with exercise and that a genetic variant in the MOTS-c sequence is linked to diabetes risk in Japanese men. PeptideAgent grades the evidence animal-only.", "source_ids": [ "lee-2015", "zempo-2021", "reynolds-2021" ] }, { "q": "Is MOTS-c an exercise mimetic?", "a": "That is the claim from mouse data. In the 2021 Nature Communications study, MOTS-c rose in muscle and plasma of young men after exercise, and injecting it improved treadmill performance in young, middle aged, and old mice. Whether injecting it improves fitness or physical function in people has not been tested.", "source_ids": [ "reynolds-2021" ] }, { "q": "What are the side effects of MOTS-c?", "a": "There is no systematic human safety data. Anecdotal reports mention injection site irritation. Because it activates AMPK and increases glucose uptake in mice, low blood sugar is a theoretical concern, especially alongside diabetes medications, but this has not been studied in people.", "source_ids": [ "lee-2015" ] }, { "q": "How is MOTS-c taken?", "a": "Mouse studies gave it by injection into the abdominal cavity. Products sold to people are subcutaneous injection vials. No human dose finding study exists, so any human regimen is extrapolated from rodent work rather than measured. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "lee-2015", "reynolds-2021" ] }, { "q": "How much does MOTS-c cost?", "a": "There is no lawful compounded price: it is not on the 503A bulks list, and advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is MOTS-c banned by WADA?", "a": "Yes. MOTS-c is named on the WADA Prohibited List under section S4.4 (metabolic modulators) as an activator of AMP-activated protein kinase, and it is prohibited at all times, in and out of competition.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "MOTS-c vs humanin: what is the difference?", "a": "Both are mitochondrial derived peptides encoded in the mitochondrial genome. MOTS-c (16 amino acids, from the 12S rRNA region) acts mainly on metabolism through AMPK. Humanin (24 amino acids, from the 16S rRNA region) was discovered as a neuroprotective factor and acts on cell survival and insulin signaling. Both have mouse data and human blood level associations only; neither has a published human treatment trial. MOTS-c was recommended for the compounding bulks list in 2026; humanin has no FDA review history.", "source_ids": [ "lee-2015", "reynolds-2021" ] } ], "studies": [ { "pmid": "25738459", "title": "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance", "year": 2015, "design": "Mouse studies with cell culture mechanism work", "population": "Mice on high fat diet and aged mice; cultured muscle cells", "outcome": "MOTS-c prevented diet induced obesity and insulin resistance and improved insulin sensitivity in aged mice through folate cycle inhibition and AMPK activation", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/25738459/" }, { "pmid": "33473109", "title": "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis", "year": 2021, "design": "Human exercise sampling study plus mouse treatment studies", "n": 10, "population": "10 healthy young men (sampling only) and young, middle aged, and old mice (treatment)", "outcome": "MOTS-c rose in human muscle and plasma after exercise; treated mice of all ages improved running capacity and late life treatment improved physical performance", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/33473109/" }, { "pmid": "33468709", "title": "A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c", "year": 2021, "design": "Genetic association study with cell and mouse functional work", "population": "Japanese adults with and without type 2 diabetes", "outcome": "The m.1382A>C variant (MOTS-c K14Q) was associated with type 2 diabetes in men and the variant peptide had reduced metabolic activity", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/33468709/" } ], "sources": [ { "id": "lee-2015", "type": "pubmed", "title": "Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25738459/", "pmid": "25738459", "year": 2015 }, { "id": "reynolds-2021", "type": "pubmed", "title": "Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33473109/", "pmid": "33473109", "year": 2021 }, { "id": "zempo-2021", "type": "pubmed", "title": "Zempo H et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY) 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33468709/", "pmid": "33468709", "year": 2021 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S4.4 metabolic modulators", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 } ], "related": [ "humanin", "ss-31", "nad-plus", "epitalon" ], "cluster": "longevity", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "MOTS-c peptide: benefits, side effects, and legal status", "description": "What MOTS-c peptide is, what the mouse metabolic and exercise studies show, side effects, and its 2026 FDA compounding status.", "h1": "MOTS-c peptide", "headings": { "evidence": "MOTS-c benefits: what the evidence shows", "safety": "MOTS-c side effects" } } }, { "slug": "humanin", "name": "Humanin", "aliases": [ "HN", "HNG (S14G-humanin analog)", "MT-RNR2 peptide", "Mitochondrial derived peptide humanin", "Humanin peptide" ], "class": "Mitochondrial derived peptide (24 amino acids) encoded in the 16S rRNA region of mitochondrial DNA", "one_liner": "A 24 amino acid peptide coded by mitochondrial DNA, protective in cells and rodents and tied to blood levels in people; no human treatment trials.", "summary": "Humanin is a 24 amino acid peptide encoded by mitochondrial DNA (the separate genetic code inside the cell's energy-producing mitochondria) that was discovered in 2001 as a factor protecting neurons from Alzheimer's disease related toxicity. In rodents it and its potent analogs (modified versions) improve insulin sensitivity, protect the heart and brain from injury, and in mice a humanin analog extended healthspan (years lived in good health); in people, circulating levels fall with age and correlate with coronary endothelial function (how well the lining of the heart arteries works), but no human treatment trial has been published. It has never been reviewed by FDA, is prohibited by WADA under section S0 (the anti-doping ban on unapproved substances), and is not available through licensed channels.", "mechanism": "Humanin is translated from a short open reading frame in the mitochondrial 16S rRNA gene (MT-RNR2). Inside cells it binds the pro-apoptotic proteins Bax and IGFBP-3 to block apoptosis. Outside cells it signals through a receptor complex of CNTFR, WSX-1, and gp130 that activates STAT3, and through the formyl peptide receptor-like 1. In rodents, central and peripheral humanin increases hypothalamic STAT3 signaling and improves hepatic insulin sensitivity. Circulating levels decline with age in humans and rodents. Mechanisms are established in cells and animals only.", "evidence_grade": "animal_only", "evidence_summary": "Cell studies show humanin protects neurons from amyloid beta and familial Alzheimer's mutations. Rodent studies show that humanin and its analog HNG improve insulin action, reduce infarct size in heart and brain injury models, and that HNG treatment of middle aged mice improved metabolic healthspan and memory. Human evidence is observational: circulating humanin declines with age, and in 40 patients undergoing coronary testing higher levels were associated with preserved endothelial function. No human intervention trial of humanin or an analog has been published. The human study is an association study of endogenous humanin levels, not an intervention with the peptide; it is listed but does not raise the grade.", "human_evidence": "No indexed human treatment trial identified. Widmer et al. 2013 measured plasma humanin in 40 patients with chest pain and non-obstructive coronary disease and found higher levels in those with normal coronary endothelial function. Yen et al. 2020 reported that circulating humanin declines with age in humans and that levels were higher in the offspring of centenarians, an association study rather than a treatment effect.", "animal_evidence": "Hashimoto et al. 2001 identified humanin as a factor that rescues cultured neurons from death caused by familial Alzheimer's disease genes and amyloid beta. Muzumdar et al. 2009 showed that central or peripheral humanin and its analog HNG improved hepatic insulin sensitivity in rats through hypothalamic STAT3. Yen et al. 2020 showed that HNG given twice weekly to middle aged mice improved metabolic healthspan and memory without extending mean life span, and that humanin overexpression in worms extended life span.", "conditions": [ "longevity", "cognitive-decline" ], "literature_dosing": "Not established in human literature. Rodent studies used humanin or HNG in the range of 0.1 to 4 mg/kg by intraperitoneal injection, and 2 to 4 mg/kg HNG twice weekly in the mouse healthspan study. No human dose finding or pharmacokinetic study has been published.", "routes": [ "Subcutaneous injection (as sold)", "Intraperitoneal and intracerebroventricular injection (animal studies)" ], "side_effects": [ "No systematic human safety data published", "Injection site reactions reported anecdotally", "Theoretical concern that an anti-apoptotic, STAT3 activating peptide could support tumor cell survival (not demonstrated in humans)" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive glucose lowering with insulin or oral diabetes drugs, based on rodent insulin sensitivity data (not tested)" ], "contraindications": [ "Active cancer or history of cancer (theoretical anti-apoptotic concern)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Humanin is not an FDA approved drug and PeptideAgent has not identified it on the FDA 503A bulks nomination lists or in any Pharmacy Compounding Advisory Committee review. Without a listing, a 503A pharmacy cannot lawfully compound it as a bulk substance. It is not eligible for 503B outsourcing. Products sold under this name are not lawful for human use.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available: no approved product and no 503A bulks listing.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is humanin legal in the United States?", "a": "It is not an FDA approved drug and is not on the FDA 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), so a compounding pharmacy cannot lawfully make it. Possessing it is not a crime, but the only products on the market are research chemicals that are not lawful for human use. Unlike MOTS-c and epitalon, humanin was not part of the 2026 advisory committee recommendations.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does humanin protect the brain or prevent Alzheimer's disease?", "a": "In cultured neurons and rodents, humanin protects against amyloid beta toxicity and improves memory in treated mice. No human trial has tested whether it prevents or treats Alzheimer's disease or cognitive decline. The human data are limited to blood levels, which fall with age. PeptideAgent grades the evidence animal-only.", "source_ids": [ "hashimoto-2001", "yen-2020" ] }, { "q": "Does humanin extend lifespan?", "a": "In worms, overexpressing humanin extended life span. In middle aged mice, the analog HNG improved metabolic health and memory but did not extend mean life span. In humans, higher humanin levels were seen in children of centenarians, which is an association, not proof that giving humanin adds years. No human longevity trial exists.", "source_ids": [ "yen-2020" ] }, { "q": "What are the side effects of humanin?", "a": "There is no systematic human safety data. Anecdotal reports mention injection site irritation. Because humanin blocks apoptosis and activates STAT3, a theoretical concern is that it could help cancer cells survive; this has not been studied in people. Rodent studies have not reported toxicity at the doses used.", "source_ids": [ "hashimoto-2001", "muzumdar-2009" ] }, { "q": "How is humanin taken?", "a": "In animal studies it was injected into the abdominal cavity, into the brain, or under the skin. Products sold to people are subcutaneous injection vials. No human dose finding or absorption study exists. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "muzumdar-2009", "yen-2020" ] }, { "q": "Is humanin banned by WADA?", "a": "Yes. Humanin has no current approval from any government health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "Humanin vs MOTS-c: which has better evidence?", "a": "Both are mitochondrial derived peptides with mouse data and human blood level associations only. MOTS-c has the stronger metabolic and exercise data in mice and was recommended for the FDA 503A bulks list in July 2026. Humanin has the older neuroprotection literature and a mouse healthspan study but no compounding pathway. Neither has a published human treatment trial.", "source_ids": [ "yen-2020", "widmer-2013", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "11371646", "title": "A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta", "year": 2001, "design": "Cell culture discovery study", "population": "Cultured neuronal cells expressing familial Alzheimer's disease mutations or exposed to amyloid beta", "outcome": "Identified humanin as a 24 amino acid peptide that abolished neuronal death caused by familial Alzheimer's disease genes and amyloid beta", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/11371646/" }, { "pmid": "19623253", "title": "Humanin: a novel central regulator of peripheral insulin action", "year": 2009, "design": "Rat clamp studies with central and peripheral peptide administration", "population": "Rats", "outcome": "Humanin and its analog HNG improved hepatic insulin sensitivity through hypothalamic STAT3 signaling", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/19623253/" }, { "pmid": "23220334", "title": "Circulating humanin levels are associated with preserved coronary endothelial function", "year": 2013, "design": "Cross sectional observational study", "n": 40, "population": "Patients with chest pain and non-obstructive coronary artery disease undergoing endothelial function testing", "outcome": "Higher plasma humanin was associated with normal coronary endothelial function", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/23220334/" }, { "pmid": "32575074", "title": "The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan", "year": 2020, "design": "Worm and mouse treatment studies plus human cohort measurements", "population": "C. elegans, middle aged mice, and human cohorts including offspring of centenarians", "outcome": "Humanin overexpression extended worm life span; HNG improved metabolic healthspan and memory in mice; circulating humanin declined with age in humans and was higher in centenarian offspring", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/32575074/" } ], "sources": [ { "id": "hashimoto-2001", "type": "pubmed", "title": "Hashimoto Y et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11371646/", "pmid": "11371646", "year": 2001 }, { "id": "muzumdar-2009", "type": "pubmed", "title": "Muzumdar RH et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19623253/", "pmid": "19623253", "year": 2009 }, { "id": "widmer-2013", "type": "pubmed", "title": "Widmer RJ et al. Circulating humanin levels are associated with preserved coronary endothelial function. Am J Physiol Heart Circ Physiol 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23220334/", "pmid": "23220334", "year": 2013 }, { "id": "yen-2020", "type": "pubmed", "title": "Yen K et al. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY) 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32575074/", "pmid": "32575074", "year": 2020 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "mots-c", "ss-31", "nad-plus" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Humanin peptide: evidence and legal status", "h1": "Humanin peptide" } }, { "slug": "ss-31", "name": "SS-31 (elamipretide)", "aliases": [ "Elamipretide", "Forzinity", "MTP-131", "Bendavia", "D-Arg-Dmt-Lys-Phe-NH2", "Szeto-Schiller peptide 31", "SS31", "SS-31 peptide", "SS31 peptide" ], "class": "Synthetic mitochondria targeted tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that binds cardiolipin on the inner mitochondrial membrane", "one_liner": "Mitochondria targeted peptide FDA approved in 2025 as Forzinity for rare Barth syndrome, after a large mitochondrial muscle disease RCT missed its main goal.", "summary": "SS-31 (elamipretide) is a four amino acid peptide that concentrates in mitochondria, the cell's energy producers, and binds cardiolipin to stabilize the electron transport chain, the machinery that makes cellular energy. It received FDA accelerated approval (an early approval that still requires confirmatory evidence) in September 2025 as Forzinity for Barth syndrome, a rare mitochondrial disease, based on a small crossover trial (each patient got drug and placebo in turn) plus open label extension data, while the 218 person MMPOWER-3 trial in primary mitochondrial myopathy (inherited muscle weakness from faulty mitochondria) did not meet its primary endpoints for walking distance or fatigue. It is available only by prescription for its approved indication, and the research chemical versions sold as SS-31 are not lawful for human use.", "mechanism": "Elamipretide is a cell permeable, aromatic cationic tetrapeptide that accumulates in the inner mitochondrial membrane and binds cardiolipin, the phospholipid that organizes respiratory chain supercomplexes. By stabilizing cardiolipin and cristae structure it improves electron transport efficiency, increases ATP production, and reduces reactive oxygen species generation during ischemia and reperfusion. These effects were shown in isolated mitochondria and rodent models and are the basis for trials in mitochondrial diseases, heart failure, and eye disease.", "evidence_grade": "human_rct", "evidence_summary": "Multiple randomized human trials with mixed results. TAZPOWER (12 boys and men with Barth syndrome, 12 week crossover) did not meet its primary endpoints, but the 168 week open label extension showed sustained improvements in 6 minute walk distance and muscle strength that supported accelerated approval. MMPOWER-3 (218 adults with primary mitochondrial myopathy, 24 weeks of 40 mg daily) showed no significant difference from placebo in 6 minute walk distance or fatigue score. Earlier phase 2 trials in heart failure and other conditions were also negative or inconclusive. Elamipretide is generally well tolerated apart from injection site reactions.", "human_evidence": "TAZPOWER (Reid Thompson 2021): 12 participants with Barth syndrome, 40 mg subcutaneously daily versus placebo in a 12 week crossover; primary endpoints (6 minute walk test and fatigue) did not differ significantly, but the open label extension showed improvement in 6 minute walk distance and knee extensor strength over 36 weeks and sustained gains at 168 weeks (Thompson 2024). MMPOWER-3 (Karaa 2023): 218 adults with genetically confirmed primary mitochondrial myopathy randomized to 40 mg daily or placebo for 24 weeks; no significant difference in 6 minute walk distance (least squares mean difference about 4 meters) or total fatigue score; injection site reactions were the main adverse events.", "animal_evidence": "In isolated mitochondria and rodent ischemia models, SS-31 binds cardiolipin, restores respiratory chain function, re-energizes ischemic mitochondria, and reduces reperfusion injury in kidney and heart. Rodent studies also report improvements in aged muscle mitochondrial function and in models of heart failure and retinal disease. These preclinical results informed the human trial program.", "conditions": [ "longevity", "muscle-recovery" ], "literature_dosing": "Clinical trials in Barth syndrome (TAZPOWER) and primary mitochondrial myopathy (MMPOWER-3) used 40 mg subcutaneously once daily. The Forzinity prescribing information on DailyMed gives the approved weight based dosing for Barth syndrome; PeptideAgent does not restate label dosing beyond the trial regimen. No dose has been established for any other use.", "routes": [ "Subcutaneous injection once daily (Forzinity label and trials)", "Intravenous infusion (earlier cardiac and kidney trials)" ], "side_effects": [ "Injection site reactions (erythema, pruritus, pain), the most common adverse event in every trial", "Headache", "Dizziness", "Eosinophilia reported in some trial participants", "Long term safety beyond the extension studies is not established" ], "interactions": [ "No clinically significant drug interactions were identified in the trial program; consult the Forzinity label for current information", "No formal interaction studies with other mitochondrial supplements such as coenzyme Q10 or NAD precursors" ], "contraindications": [ "No contraindications listed in the approved label as of the last verification date; check DailyMed for updates", "Pregnancy and breastfeeding: no adequate human data", "Use outside the approved indication should be limited to clinical trials" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA granted accelerated approval to elamipretide (Forzinity) in September 2025 for Barth syndrome, making it the first approved treatment for that disease. Because an FDA approved product exists, elamipretide is not eligible for routine 503A compounding, and it has not been listed on the 503A bulks list. Material sold online as SS-31 for research use is not the approved drug and is not lawful for human use.", "typical_cost": "Forzinity pricing for Barth syndrome is set for a rare disease and is largely covered through specialty pharmacy and manufacturer patient programs; a cash price is not publicly listed. Research chemical listings for SS-31 exist but those products are not lawful for human use.", "access_path": [ "Prescription from a specialist for Barth syndrome, dispensed through specialty pharmacy as Forzinity.", "Clinical trials for other mitochondrial and age related conditions.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is SS-31 peptide?", "a": "SS-31, now named elamipretide, is a synthetic four amino acid peptide that concentrates in mitochondria, the cell's energy producers, and binds cardiolipin, a lipid that holds the energy producing machinery together. FDA approved it as Forzinity to improve muscle strength in patients with Barth syndrome, a rare inherited mitochondrial disease, weighing at least 30 kg, under accelerated approval, an early approval that still requires confirmatory evidence. SS-31 sold online for energy or anti-aging is not the approved product and is not lawful for human use.", "source_ids": [ "birk-2013", "dailymed-forzinity" ] }, { "q": "Is SS-31 (elamipretide) FDA approved?", "a": "Yes, for one indication. FDA granted accelerated approval to elamipretide as Forzinity in September 2025 for Barth syndrome, a rare inherited mitochondrial disease. It is not approved for primary mitochondrial myopathy, heart failure, aging, or athletic performance, and it is available only by prescription.", "source_ids": [ "dailymed-forzinity", "reid-thompson-2021" ] }, { "q": "Does elamipretide work for mitochondrial disease?", "a": "The evidence is mixed. In Barth syndrome, the 12 person TAZPOWER crossover missed its primary endpoints, but the open label extension showed sustained gains in walking distance and strength over 168 weeks, which was enough for accelerated approval. In primary mitochondrial myopathy, the 218 person MMPOWER-3 trial found no significant improvement in walking distance or fatigue versus placebo.", "source_ids": [ "reid-thompson-2021", "thompson-2024", "karaa-2023" ] }, { "q": "What are the side effects of elamipretide?", "a": "Injection site reactions such as redness, itching, and pain are by far the most common adverse event and occurred in most treated participants in MMPOWER-3. Headache and dizziness were also reported. Serious adverse events were not more common than placebo in the randomized trials, but long term safety data come from small open label extensions.", "source_ids": [ "karaa-2023", "thompson-2024" ] }, { "q": "What is the elamipretide (Forzinity) dose on the FDA label?", "a": "The Forzinity label dose for Barth syndrome patients weighing at least 30 kg is 40 mg injected under the skin once daily, at the same time each day. Adults with severe kidney impairment (eGFR under 30 mL per minute and not on dialysis) take 20 mg once daily. A missed dose is skipped, not doubled. The Barth syndrome and mitochondrial myopathy trials also used 40 mg daily.", "source_ids": [ "dailymed-forzinity", "karaa-2023" ] }, { "q": "How much does elamipretide cost?", "a": "Forzinity is priced as a rare disease drug and dispensed through specialty pharmacies, usually with insurance coverage and manufacturer support for eligible Barth syndrome patients; no public cash price was verified. SS-31 sold by research chemical sellers is not the approved product and is not lawful for human use.", "source_ids": [ "dailymed-forzinity" ] }, { "q": "Is SS-31 banned by WADA?", "a": "Elamipretide is an FDA approved drug and is not named in any section of the WADA Prohibited List as of the 2026 list or the 2027 list published in September 2026, so it is not prohibited. Athletes should still confirm with their anti-doping organization, because unapproved research versions and future list changes could alter that answer.", "source_ids": [ "wada-list", "dailymed-forzinity", "wada-2027-list" ] }, { "q": "Does SS-31 work as an anti-aging or longevity peptide?", "a": "No human trial has tested elamipretide for aging. In rodents it improves mitochondrial function in aged muscle and heart, which drives the longevity marketing. The human trials are in genetic mitochondrial diseases, and the largest one was negative. There is no evidence in healthy adults.", "source_ids": [ "birk-2013", "karaa-2023" ] }, { "q": "SS-31 vs MOTS-c: what is the difference?", "a": "Both target mitochondria, but SS-31 (elamipretide) is a synthetic drug that binds cardiolipin and has an FDA approval and several randomized trials, while MOTS-c is a natural mitochondrial encoded peptide with mouse data only and no human trial. Elamipretide is a prescription product; MOTS-c is awaiting an FDA compounding rule after a 2026 advisory committee recommendation.", "source_ids": [ "dailymed-forzinity", "birk-2013" ] } ], "studies": [ { "pmid": "23813215", "title": "The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin", "year": 2013, "design": "Mechanistic study in isolated mitochondria and rat kidney ischemia model", "population": "Isolated mitochondria and rats", "outcome": "SS-31 bound cardiolipin, restored electron transport and ATP synthesis after ischemia, and reduced reperfusion injury", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/23813215/" }, { "pmid": "33077895", "title": "A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER)", "year": 2021, "design": "Randomized, double blind, placebo controlled 12 week crossover followed by open label extension", "n": 12, "population": "Boys and men with genetically confirmed Barth syndrome", "outcome": "Primary endpoints not met in the crossover; open label extension showed improved 6 minute walk distance and muscle strength at 36 weeks", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33077895/" }, { "pmid": "37268435", "title": "Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial", "year": 2023, "design": "Randomized, double blind, placebo controlled trial, 24 weeks", "n": 218, "population": "Adults with genetically confirmed primary mitochondrial myopathy", "outcome": "No significant difference from placebo in 6 minute walk distance or total fatigue score; injection site reactions were the main adverse event", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37268435/" }, { "pmid": "38602181", "title": "Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER", "year": 2024, "design": "Open label extension of a randomized trial", "n": 10, "population": "Participants with Barth syndrome who continued elamipretide", "outcome": "Sustained improvements in 6 minute walk distance, muscle strength, and cardiac stroke volume over 168 weeks; injection site reactions common", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/38602181/" } ], "sources": [ { "id": "birk-2013", "type": "pubmed", "title": "Birk AV et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23813215/", "pmid": "23813215", "year": 2013 }, { "id": "reid-thompson-2021", "type": "pubmed", "title": "Reid Thompson W et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genet Med 2021 (TAZPOWER)", "url": "https://pubmed.ncbi.nlm.nih.gov/33077895/", "pmid": "33077895", "year": 2021 }, { "id": "karaa-2023", "type": "pubmed", "title": "Karaa A et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37268435/", "pmid": "37268435", "year": 2023 }, { "id": "thompson-2024", "type": "pubmed", "title": "Thompson WR et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38602181/", "pmid": "38602181", "year": 2024 }, { "id": "dailymed-forzinity", "type": "fda", "title": "FDA prescribing information for Forzinity (elamipretide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 } ], "related": [ "mots-c", "humanin", "nad-plus" ], "cluster": "longevity", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "SS-31 (elamipretide): evidence and approval status", "description": "SS-31 peptide, now elamipretide (Forzinity): what it is, the Barth syndrome approval, trial results, side effects, and the FDA label dose.", "h1": "SS-31 peptide (elamipretide, Forzinity)", "headings": { "evidence": "SS-31 benefits: what the evidence shows", "safety": "SS-31 side effects" } } }, { "slug": "nad-plus", "name": "NAD+", "aliases": [ "Nicotinamide adenine dinucleotide", "NAD", "IV NAD+", "NAD+ injection", "Precursors: nicotinamide riboside (NR), nicotinamide mononucleotide (NMN)", "NAD injections", "NAD+ IV therapy", "NAD IV drip" ], "class": "Coenzyme (a dinucleotide, not a peptide) central to redox metabolism and sirtuin and PARP signaling; sold as intravenous or subcutaneous NAD+ and as oral precursors", "one_liner": "A coenzyme, not a peptide, whose precursors raise blood NAD+ in human RCTs; clinical benefits and IV NAD+ itself remain largely unproven.", "summary": "NAD+ is a coenzyme found in every cell that declines with age; it is not a peptide but is marketed alongside peptides as injections and infusions. Randomized trials show that oral precursors such as nicotinamide riboside and nicotinamide mononucleotide reliably raise blood NAD+ and that NMN modestly improved muscle insulin sensitivity in 25 prediabetic women, but hard clinical outcomes have not been demonstrated and intravenous NAD+ has only an 11 person pharmacokinetic pilot. NAD+ was nominated for the FDA 503A bulks list and has no final FDA determination, so compounded injections sit in a gray area, while oral precursors are sold as dietary supplements.", "mechanism": "NAD+ shuttles electrons in glycolysis, the citric acid cycle, and oxidative phosphorylation, and is consumed as a substrate by sirtuins, PARP DNA repair enzymes, and CD38. Tissue NAD+ falls with age, partly because CD38 activity rises. Oral precursors (NR, NMN, niacin) enter the salvage pathway and raise cellular NAD+. Intravenous NAD+ is largely broken down in blood to nicotinamide and other metabolites before reaching cells, which is why the pharmacology of infusions differs from oral precursors.", "evidence_grade": "human_rct", "evidence_summary": "Human randomized trials exist mainly for precursors. Martens et al. 2018 (24 healthy middle aged and older adults, crossover, 6 weeks of NR 1,000 mg per day) found NR raised blood NAD+ by about 60% and was well tolerated, with a nonsignificant trend to lower blood pressure. Yoshino et al. 2021 (25 postmenopausal prediabetic women, 10 weeks of NMN 250 mg per day) found improved muscle insulin sensitivity by about 25% without changes in body composition or other metabolic markers. A 2025 meta-analysis found no meaningful effect of NR or NMN on muscle mass or function. For intravenous NAD+ itself, the only published human study is an 11 person pilot describing plasma and urine metabolites during a 6 hour infusion. A 2018 review summarizes the in vivo evidence for NAD boosting molecules, which is mostly rodent.", "human_evidence": "Martens 2018: 24 adults aged 55 to 79, randomized crossover, NR 500 mg twice daily for 6 weeks raised blood NAD+ metabolome and was well tolerated; secondary blood pressure and arterial stiffness changes were not significant. Yoshino 2021: 25 overweight or obese postmenopausal women with prediabetes, NMN 250 mg per day for 10 weeks, muscle insulin stimulated glucose disposal improved about 25% versus no change on placebo, with no change in body weight, fat, or fasting glucose. Grant 2019: 11 healthy men received a 6 hour intravenous infusion of NAD+ at 3 umol per minute; plasma NAD+ did not rise until the second hour and metabolites accumulated in urine, with no clinical endpoints. Prokopidis 2025 meta-analysis: NR and NMN did not improve muscle mass or physical function across pooled trials.", "animal_evidence": "In mice, NR, NMN, and other NAD boosting strategies improve mitochondrial function, insulin sensitivity, and exercise capacity, and in some models extend life span or healthspan; sirtuin activation is the proposed pathway. Rajman, Chwalek, and Sinclair 2018 review the in vivo rodent evidence and note that human data lag well behind.", "conditions": [ "longevity", "type-2-diabetes" ], "literature_dosing": "Oral nicotinamide riboside 1,000 mg per day (500 mg twice daily) for 6 weeks (Martens 2018) and nicotinamide mononucleotide 250 mg per day for 10 weeks (Yoshino 2021) were the regimens used in randomized trials. The only intravenous NAD+ study infused 750 mg over 6 hours in 11 healthy men (Grant 2019). No clinical outcome based dose has been established for NAD+ infusions or injections.", "routes": [ "Oral precursors: nicotinamide riboside, nicotinamide mononucleotide (dietary supplements)", "Intravenous infusion of NAD+ (clinics, compounded)", "Subcutaneous or intramuscular NAD+ injection (compounded)", "Intranasal and transdermal products exist without absorption data" ], "side_effects": [ "Oral NR and NMN: generally well tolerated in trials; mild nausea, flushing, and fatigue reported", "IV NAD+: infusion related chest pressure, nausea, cramping, flushing, and anxiety when given quickly (reported clinically; drives slow infusion rates)", "Injection site reactions with subcutaneous NAD+", "Long term safety of chronically elevated NAD+ is unknown; theoretical concern about supporting tumor metabolism in animal models" ], "interactions": [ "No formal interaction studies for NAD+ infusions", "NAD precursors may add to the flushing of niacin containing products", "Theoretical interaction with PARP inhibitors used in oncology, since NAD+ is their substrate (not tested)" ], "contraindications": [ "Active cancer without oncologist input (theoretical, based on tumor metabolism in animal models)", "Pregnancy and breastfeeding (no data for injections or infusions)", "Rapid IV infusion in people with cardiac disease, given reported infusion reactions" ], "wada_status": "not_prohibited", "fda_status": "under_review", "compounding_status": "NAD+ (nicotinamide adenine dinucleotide) is not an FDA approved drug. It was nominated for the FDA 503A bulks list and appears on the nominated substances lists pending FDA evaluation; no final rule placing it on or excluding it from the bulks list had been published as of the last verification date, so compounded NAD+ injections and infusions are dispensed under FDA's interim enforcement policy where state boards permit. Oral NR and NMN are sold as dietary supplements, and FDA has questioned whether NMN qualifies as a dietary ingredient because of prior drug investigation.", "typical_cost": "IV NAD+ at a published clinic menu costs about 450 to 900 USD per session for 500 to 1,000 mg (member prices from 400 USD); compounded subcutaneous NAD+ through telehealth is about 79 to 199 USD per month. Oral NR or NMN supplements are sold over the counter. Prices checked 2026-09-22 on published provider and pharmacy price pages.", "access_path": [ "Over the counter dietary supplement precursors (nicotinamide riboside, nicotinamide mononucleotide), no prescription needed.", "Prescription from a licensed provider filled by a 503A compounding pharmacy for injectable NAD+, where the state board permits it.", "Clinic or telehealth programs offering NAD+ infusions or injections." ], "faqs": [ { "q": "What are NAD+ injections?", "a": "NAD+ injections are shots of nicotinamide adenine dinucleotide, a coenzyme found in every cell, usually given under the skin or into a muscle; NAD+ IV therapy infuses it into a vein over several hours. NAD+ is a coenzyme, not a peptide, though it is often sold alongside peptides. Both forms are compounded, not FDA approved: NAD+ has been nominated for the 503A bulks list without a final decision. No trial has tested NAD+ injections for a clinical outcome, and the only published IV study is an 11 person pilot.", "source_ids": [ "fda-503a-bulks", "grant-2019", "rajman-2018" ] }, { "q": "NAD+ IV therapy: what does the evidence show?", "a": "There is almost no evidence either way. The only published human study of intravenous NAD+ was an 11 person pilot that measured blood and urine metabolites during a 6 hour infusion and found much of the dose was broken down or excreted. No trial has compared IV NAD+ with oral precursors or measured clinical outcomes, so the several hundred dollar price is paid for an unproven benefit.", "source_ids": [ "grant-2019", "martens-2018", "price-iv-clinic" ] }, { "q": "What are the benefits of NAD+, and are they proven?", "a": "Not proven. Precursors reliably raise blood NAD+ in human trials, and one 25 person trial found NMN improved muscle insulin sensitivity by about 25% in prediabetic women. But no human trial has shown slower aging, longer life, or better physical function; a 2025 meta-analysis found no effect of NR or NMN on muscle mass or function. The longevity claims come from mouse studies.", "source_ids": [ "yoshino-2021", "prokopidis-2025", "rajman-2018" ] }, { "q": "What are the side effects of NAD+?", "a": "Oral NR and NMN were well tolerated in randomized trials, with occasional mild nausea, flushing, or fatigue. IV NAD+ commonly causes chest pressure, nausea, cramping, and flushing when infused quickly, which is why clinics run it over hours. Long term safety of pushing NAD+ levels up is unknown, and animal work raises a theoretical concern about feeding tumor metabolism.", "source_ids": [ "martens-2018", "grant-2019", "rajman-2018" ] }, { "q": "Is NAD+ legal, and is it FDA approved?", "a": "NAD+ is not an FDA approved drug. Oral precursors such as nicotinamide riboside are lawful dietary supplements. Injectable and intravenous NAD+ are compounded from a bulk substance that has been nominated for the FDA 503A bulks list but has no final determination, so clinics offer it under FDA's interim enforcement discretion where state boards allow. Possessing or receiving it is not a crime.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "How is NAD+ taken in studies?", "a": "Trials used oral nicotinamide riboside 1,000 mg per day for 6 weeks and oral nicotinamide mononucleotide 250 mg per day for 10 weeks. The one IV study infused 750 mg over 6 hours. Clinic infusion and subcutaneous injection doses vary widely and have not been studied for outcomes.", "source_ids": [ "martens-2018", "yoshino-2021", "grant-2019" ] }, { "q": "NAD+ vs NMN vs NR: which is better?", "a": "For raising blood NAD+, oral NR and NMN both work in randomized trials. NR has the larger safety database (Martens 2018 and others); NMN has the one trial showing a metabolic benefit (Yoshino 2021). Direct IV NAD+ has a single pharmacokinetic pilot and no outcome data. FDA has questioned NMN's status as a dietary ingredient, so its availability is less settled than NR's.", "source_ids": [ "martens-2018", "yoshino-2021", "grant-2019" ] }, { "q": "Is NAD+ banned by WADA?", "a": "No. NAD+ and its precursors are naturally occurring vitamin B3 metabolites and are not listed in any section of the WADA Prohibited List as of 2026. Athletes should still verify supplement purity, since contamination is the main doping risk with supplements.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "29599478", "title": "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults", "year": 2018, "design": "Randomized, double blind, placebo controlled crossover trial, 6 weeks per arm", "n": 24, "population": "Healthy adults aged 55 to 79", "outcome": "NR 1,000 mg per day raised blood NAD+ metabolome by about 60% and was well tolerated; nonsignificant trend toward lower blood pressure", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/29599478/" }, { "pmid": "33888596", "title": "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women", "year": 2021, "design": "Randomized, double blind, placebo controlled trial, 10 weeks", "n": 25, "population": "Overweight or obese postmenopausal women with prediabetes", "outcome": "NMN 250 mg per day improved muscle insulin stimulated glucose disposal by about 25%; no change in body composition, fasting glucose, or other metabolic markers", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33888596/" }, { "pmid": "31572171", "title": "A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+", "year": 2019, "design": "Open label pharmacokinetic pilot", "n": 11, "population": "Healthy adult men", "outcome": "Plasma NAD+ did not rise until the second hour of infusion; metabolites accumulated in urine; no clinical endpoints", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/31572171/" }, { "pmid": "40275690", "title": "The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis", "year": 2025, "design": "Systematic review and meta-analysis of randomized trials", "population": "Adults in randomized trials of NR or NMN", "outcome": "No significant effect of NR or NMN on muscle mass or physical function", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/40275690/" } ], "sources": [ { "id": "martens-2018", "type": "pubmed", "title": "Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29599478/", "pmid": "29599478", "year": 2018 }, { "id": "yoshino-2021", "type": "pubmed", "title": "Yoshino M et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33888596/", "pmid": "33888596", "year": 2021 }, { "id": "grant-2019", "type": "pubmed", "title": "Grant R et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31572171/", "pmid": "31572171", "year": 2019 }, { "id": "prokopidis-2025", "type": "pubmed", "title": "Prokopidis K et al. The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40275690/", "pmid": "40275690", "year": 2025 }, { "id": "rajman-2018", "type": "pubmed", "title": "Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29514064/", "pmid": "29514064", "year": 2018 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-iv-clinic", "type": "other", "title": "Registered nurse staffed IV clinic published price menu (NAD+ and glutathione), accessed 2026-09-22", "url": "https://hydrateivbar.com/pricing/" } ], "related": [ "mots-c", "ss-31", "glutathione", "humanin" ], "cluster": "longevity", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "NAD+ injections and IV therapy: evidence and legality", "description": "What NAD+ injections and IV drips are, what human trials show about benefits and side effects, how oral precursors compare, and where NAD+ stands legally.", "h1": "NAD+ injections and IV therapy", "headings": { "summary": "What are NAD+ injections?", "evidence": "NAD+ IV therapy: what the evidence shows", "safety": "NAD+ side effects and interactions" } } }, { "slug": "foxo4-dri", "name": "FOXO4-DRI", "aliases": [ "FOXO4 D-retro-inverso peptide", "FOXO4-DRI senolytic", "Proxofim", "FOXO4 DRI" ], "class": "Synthetic D-amino acid retro-inverso peptide (about 46 residues) that disrupts the FOXO4 to p53 interaction in senescent cells", "one_liner": "A senolytic peptide that clears senescent cells and restored fitness, fur, and kidney function in aged mice; no human data exist.", "summary": "FOXO4-DRI is a synthetic cell penetrating peptide built from D-amino acids in reverse order so it resists breakdown; it pries the transcription factor FOXO4 off p53 inside senescent cells, which releases p53 to trigger their death. In a 2017 Cell paper it selectively killed senescent cells and restored running capacity, fur density, and kidney function in fast aging and naturally old mice, and later mouse studies reported improved testosterone and sperm production in old males. There is no human trial, no FDA review, and no lawful source; it is prohibited by WADA under section S0.", "mechanism": "In senescent cells, FOXO4 binds p53 in the nucleus and keeps it from triggering apoptosis, which lets damaged cells persist and secrete inflammatory factors (the senescence associated secretory phenotype). FOXO4-DRI is a D-retro-inverso version of the FOXO4 fragment that binds p53; it competes with native FOXO4, freeing p53 to move to mitochondria and start cell death selectively in senescent cells. The D-amino acid backbone resists proteases, which gives it a longer half life than a normal peptide. All of this is shown in cell culture and mice.", "evidence_grade": "animal_only", "evidence_summary": "One high profile mouse study and a few follow ups. Baar et al. 2017 showed FOXO4-DRI (5 mg/kg intraperitoneally, 3 doses over a week or repeated cycles) selectively killed senescent cells in culture and in mice, neutralized chemotherapy induced toxicity, and in fast aging XpdTTD/TTD and naturally aged mice restored fur density, running wheel activity, and kidney function markers. Zhang et al. 2020 reported that FOXO4-DRI cleared senescent Leydig cells and raised testosterone in aged mice, and Li et al. 2024 reported improved spermatogenesis in aged mice. No human study of any kind has been published.", "human_evidence": "No indexed human study identified. No pharmacokinetic, safety, or efficacy data in humans exist.", "animal_evidence": "Baar 2017: in aged and progeroid mice, FOXO4-DRI reduced senescent cell burden and improved fur density, physical activity, and renal function within weeks; in doxorubicin treated mice it reduced chemotherapy toxicity. Zhang 2020: intraperitoneal FOXO4-DRI in aged male mice removed senescent Leydig cells and raised serum testosterone. Li 2024: in aged mice, FOXO4-DRI reduced senescence associated secretory phenotype output from Leydig cells and improved spermatogenesis.", "conditions": [ "longevity" ], "literature_dosing": "Not established in human literature. Mouse studies used 5 mg/kg intraperitoneally, given as 3 doses on alternating days, sometimes repeated in cycles. No human dose, route, or pharmacokinetic study has been published.", "routes": [ "Subcutaneous injection (as sold)", "Intraperitoneal injection (animal studies)" ], "side_effects": [ "No human safety data of any kind", "Theoretical risk that a p53 activating senolytic could harm non-senescent cells or tissues that rely on transient senescence for wound healing", "Injection site reactions reported anecdotally", "D-amino acid peptides resist degradation, so persistence and immunogenicity in humans are unknown" ], "interactions": [ "No formal interaction studies exist", "Theoretical additive effects with other senolytics (dasatinib, quercetin, fisetin) and with chemotherapy that acts through p53 (not tested)" ], "contraindications": [ "Any use outside a clinical trial; no human data exist", "Active cancer (p53 pathway manipulation without human data)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "FOXO4-DRI is not an FDA approved drug and PeptideAgent has not identified it on the FDA 503A bulks nomination lists or in any Pharmacy Compounding Advisory Committee review. Without a listing, a 503A pharmacy cannot lawfully compound it as a bulk substance. It is not eligible for 503B outsourcing. Products sold under this name are not lawful for human use and, because the peptide is long and made entirely of D-amino acids, are expensive and difficult to verify.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available: no approved product, no clinical trials open to the public, and no 503A bulks listing.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is FOXO4-DRI legal in the United States?", "a": "It is not an FDA approved drug and is not on the FDA 503A bulks list, so no compounding pharmacy can lawfully make it. Possessing it is not a crime, but the only products available are research chemicals that are not lawful for human use. It has never been reviewed by FDA's compounding advisory committee.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does FOXO4-DRI reverse aging?", "a": "In mice, it produced striking results: after a short course, aged mice regrew fur, ran more, and improved kidney function markers, and senescent cells were cleared from tissues. In humans, nothing is known, because no study has ever given it to a person. PeptideAgent grades the evidence animal-only.", "source_ids": [ "baar-2017" ] }, { "q": "Does FOXO4-DRI raise testosterone?", "a": "Only in old mice so far. A 2020 study found it removed senescent Leydig cells from aged mouse testes and raised serum testosterone, and a 2024 study reported improved sperm production. No human data exist.", "source_ids": [ "zhang-2020", "li-2024" ] }, { "q": "What are the side effects of FOXO4-DRI?", "a": "Unknown in humans. The mechanism activates p53 driven cell death in senescent cells, and senescent cells play useful roles in wound healing and tumor suppression, so off target harm is a theoretical concern. The D-amino acid design makes the peptide persist longer in the body, and its immunogenicity has never been assessed in people.", "source_ids": [ "baar-2017" ] }, { "q": "How is FOXO4-DRI taken?", "a": "In mice it was given by injection into the abdominal cavity on alternating days, sometimes in repeated cycles. Products sold to people are subcutaneous injection vials. There is no human dose, and mouse regimens do not translate to people. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "baar-2017", "zhang-2020" ] }, { "q": "Is FOXO4-DRI banned by WADA?", "a": "Yes. FOXO4-DRI has no current approval from any government health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "FOXO4-DRI vs dasatinib and quercetin: which senolytic is better studied?", "a": "Dasatinib plus quercetin has small human pilot trials in diabetic kidney disease and idiopathic pulmonary fibrosis; FOXO4-DRI has none. Both cleared senescent cells in mice. FOXO4-DRI is more selective in cell studies because it targets the FOXO4 to p53 interaction, but that selectivity has never been tested in a person.", "source_ids": [ "baar-2017" ] } ], "studies": [ { "pmid": "28340339", "title": "Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging", "year": 2017, "design": "Cell culture and mouse studies (progeroid and naturally aged mice)", "population": "Cultured senescent cells; XpdTTD/TTD fast aging mice and naturally aged mice", "outcome": "FOXO4-DRI selectively induced apoptosis in senescent cells, reduced doxorubicin toxicity, and restored fur density, running activity, and kidney function markers in aged mice", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/28340339/" }, { "pmid": "31959736", "title": "FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice", "year": 2020, "design": "Mouse study with cell culture work", "population": "Aged male mice and cultured Leydig cells", "outcome": "FOXO4-DRI cleared senescent Leydig cells and increased serum testosterone in aged mice", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/31959736/" }, { "pmid": "39025385", "title": "FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells", "year": 2024, "design": "Mouse study", "population": "Aged male mice", "outcome": "FOXO4-DRI reduced senescence associated secretory phenotype output and improved spermatogenesis", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/39025385/" } ], "sources": [ { "id": "baar-2017", "type": "pubmed", "title": "Baar MP et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28340339/", "pmid": "28340339", "year": 2017 }, { "id": "zhang-2020", "type": "pubmed", "title": "Zhang C et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY) 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31959736/", "pmid": "31959736", "year": 2020 }, { "id": "li-2024", "type": "pubmed", "title": "Li Y et al. FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Exp Gerontol 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39025385/", "pmid": "39025385", "year": 2024 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "epitalon", "mots-c", "humanin" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "FOXO4-DRI: senolytic evidence and legal status" } }, { "slug": "thymalin", "name": "Thymalin", "aliases": [ "Thymalinum", "Thymus extract peptide complex", "Timalin", "Glu-Trp dipeptide (thymogen) is its synthetic derivative" ], "class": "Polypeptide extract from calf thymus (a mixture of low molecular weight peptides), registered as a drug in Russia", "one_liner": "A Russian calf thymus peptide extract used to adjust the immune system, with decades of non-randomized Russian reports and no FDA review.", "summary": "Thymalin is a peptide mixture extracted from calf thymus, the gland where immune T cells mature, that has been registered as an immunomodulating (immune adjusting) drug in Russia since the 1980s. Russian reports describe restored T cell counts and, in the developer's long term follow up of elderly patients, lower mortality, but these studies are open and non-randomized (no chance assignment to a comparison group), come mostly from one institute, and are not independently replicated. It has never been reviewed or approved by FDA, is not on the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), and is not available through licensed channels in the United States.", "mechanism": "Thymalin contains short thymic peptides, including the dipeptide Glu-Trp, that are proposed to promote differentiation and maturation of T lymphocytes and to normalize the ratio of helper to suppressor T cells. In vitro, thymalin activated differentiation of human hematopoietic stem cells and altered expression of genes involved in immune signaling in cell lines. Mechanisms come from cell studies and Russian clinical reports rather than controlled pharmacology.", "evidence_grade": "human_observational", "evidence_summary": "Human evidence is limited to non-randomized studies. Khavinson and Morozov (2003) reported that elderly patients given courses of Thymalin, with or without the pineal preparation Epithalamin, over 6 to 12 years had lower mortality and fewer infections and cardiovascular events than untreated controls; the study was open, not randomized, and from the developing institute. Khavinson et al. (2021) reported a small open study in which thymalin added to standard care in hospitalized COVID-19 patients was associated with faster normalization of inflammatory markers. In vitro work (2020) showed activation of hematopoietic stem cell differentiation. No randomized controlled trial or independent replication has been indexed.", "human_evidence": "Khavinson 2003: open, non-randomized long term follow up of elderly patients in St. Petersburg treated with Thymalin and Epithalamin courses; authors report reduced mortality over 6 to 12 years and fewer acute respiratory infections. Khavinson 2021: open comparative study of thymalin added to standard therapy in COVID-19 patients, reporting faster reduction of C-reactive protein and lymphocyte recovery; small, not randomized or blinded. No pharmacokinetic or dose ranging study has been published in English.", "animal_evidence": "Rodent and cell studies from the same group report restoration of immune function after thymectomy, radiation, or aging and stimulation of T cell differentiation. Khavinson 2020 showed thymalin activated differentiation of human hematopoietic stem cells in culture. Independent animal work is scarce.", "conditions": [ "longevity", "inflammation" ], "literature_dosing": "Not established in indexed human literature. Russian labeling describes intramuscular courses, but no dose finding trial has been published in an indexed journal, so no dose range is reported here.", "routes": [ "Intramuscular injection (Russian labeling and reports)", "Subcutaneous injection (as sold)" ], "side_effects": [ "No systematic safety data from randomized trials", "Allergic reactions are the main risk listed for a bovine tissue extract", "Injection site pain", "Theoretical prion and adventitious agent risk with unverified bovine thymus products of unknown origin" ], "interactions": [ "No formal interaction studies exist", "Theoretical opposition to immunosuppressants (corticosteroids, calcineurin inhibitors, biologics) given proposed immune stimulating action (not tested)" ], "contraindications": [ "Known hypersensitivity to bovine proteins", "Autoimmune disease or organ transplant (theoretical immune stimulation)", "Pregnancy and breastfeeding (no data)", "Competitive athletes should confirm status with their anti-doping organization" ], "wada_status": "unclear", "fda_status": "unscheduled", "compounding_status": "Thymalin is not an FDA approved drug and PeptideAgent has not identified it on the FDA 503A bulks nomination lists or in any Pharmacy Compounding Advisory Committee review. As an animal tissue extract of undefined composition it is not a candidate for 503A bulk compounding, and it is not eligible for 503B outsourcing. It is registered as a prescription drug in Russia and some neighboring countries. Products sold in the United States under this name are not lawful for human use.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available in the United States: no approved product and no 503A bulks listing.", "Prescription drug in Russia and some neighboring countries.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is thymalin legal in the United States?", "a": "It is not an FDA approved drug and is not on the FDA 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), so no US compounding pharmacy can lawfully make it. Possessing it is not a crime, but the only products on the US market are research chemicals that are not lawful for human use. It is a registered prescription drug in Russia.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does thymalin work to boost the immune system?", "a": "Russian open label reports describe restored T cell counts and fewer infections, and an in vitro study showed it activated differentiation of human blood stem cells. But no randomized, blinded trial has been published and the human data come almost entirely from one institute, so the effect size in people is unknown. PeptideAgent grades the evidence human observational.", "source_ids": [ "khavinson-2003-human", "khavinson-2020", "khavinson-2021" ] }, { "q": "Does thymalin extend lifespan?", "a": "The claim comes from a 2003 report in which elderly patients given Thymalin and Epithalamin courses had lower mortality over 6 to 12 years than untreated controls. That study was not randomized, participants were not blinded, and it has not been replicated independently, so it cannot establish that thymalin prolongs life.", "source_ids": [ "khavinson-2003-human" ] }, { "q": "What are the side effects of thymalin?", "a": "No randomized safety data exist. As a bovine thymus extract, allergic reactions are the main labeled risk, along with injection site pain. Unverified products carry the additional concern of contamination or animal derived infectious agents, since the source and processing cannot be checked.", "source_ids": [ "khavinson-2021" ] }, { "q": "How is thymalin taken?", "a": "Not established in indexed human literature. Russian labeling describes intramuscular courses given as short repeated cycles, but no dose finding trial has been published in an indexed journal, so PeptideAgent does not report a regimen.", "source_ids": [ "khavinson-2003-human", "khavinson-2021" ] }, { "q": "Is thymalin banned by WADA?", "a": "Unclear. Thymalin is not named on the WADA Prohibited List, and because it is an approved drug in Russia it does not fall automatically under section S0 for non-approved substances. However, its composition is undefined and immune modulators can be reviewed case by case, so athletes should check with their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "Thymalin vs thymosin alpha-1: what is the difference?", "a": "Thymosin alpha-1 is a single defined 28 amino acid peptide that has been approved in several countries and studied in randomized trials for hepatitis B and as a vaccine adjuvant. Thymalin is an undefined mixture of thymus peptides with only non-randomized Russian data. Neither is FDA approved, but thymosin alpha-1 has a far larger and more rigorous evidence base.", "source_ids": [ "khavinson-2003-human", "khavinson-2020" ] } ], "studies": [ { "pmid": "14523363", "title": "Peptides of pineal gland and thymus prolong human life", "year": 2003, "design": "Open, non-randomized long term follow up of elderly patients treated with thymus and pineal peptide preparations", "population": "Elderly patients in Russia treated with Thymalin and Epithalamin", "outcome": "Authors report lower mortality and fewer infections and cardiovascular events over 6 to 12 years versus untreated controls; not randomized and from the developing institute", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/14523363/" }, { "pmid": "33237528", "title": "Thymalin: activation of differentiation of human hematopoietic stem cells", "year": 2020, "design": "In vitro study", "population": "Cultured human hematopoietic stem cells", "outcome": "Thymalin increased expression of differentiation markers in cultured hematopoietic stem cells", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/33237528/" }, { "pmid": "33575961", "title": "Results and prospects of using activator of hematopoietic stem cell differentiation in complex therapy for patients with COVID-19", "year": 2021, "design": "Open comparative clinical study", "population": "Hospitalized adults with COVID-19 receiving standard therapy with or without thymalin", "outcome": "Faster normalization of inflammatory markers and lymphocyte counts reported in the thymalin group; small, not randomized or blinded", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/33575961/" } ], "sources": [ { "id": "khavinson-2003-human", "type": "pubmed", "title": "Khavinson VK, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/14523363/", "pmid": "14523363", "year": 2003 }, { "id": "khavinson-2020", "type": "pubmed", "title": "Khavinson VK et al. Thymalin: activation of differentiation of human hematopoietic stem cells. Bull Exp Biol Med 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33237528/", "pmid": "33237528", "year": 2020 }, { "id": "khavinson-2021", "type": "pubmed", "title": "Khavinson VK et al. Results and prospects of using activator of hematopoietic stem cell differentiation in complex therapy for patients with COVID-19. Stem Cell Rev Rep 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33575961/", "pmid": "33575961", "year": 2021 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "epitalon", "thymosin-alpha-1", "thymulin" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Thymalin: evidence, side effects, and legal status" } }, { "slug": "carnosine", "name": "Carnosine", "aliases": [ "L-carnosine", "Beta-alanyl-L-histidine", "Histidine containing dipeptide", "Beta-alanine (its rate limiting precursor)" ], "class": "Naturally occurring dipeptide (beta-alanine plus histidine) concentrated in skeletal muscle and brain; sold as a dietary supplement", "one_liner": "A natural muscle dipeptide with small human RCTs showing modest glycemic and waist benefits; a lawful supplement, not a drug.", "summary": "Carnosine is a dipeptide of beta-alanine and histidine that the body makes and stores in muscle and brain, where it buffers acid, chelates metals, and quenches reactive carbonyls. Small randomized trials and a 2020 meta-analysis of histidine containing dipeptides show modest improvements in fasting glucose, HbA1c, and waist circumference, and a 2016 pilot found 2 g per day prevented worsening insulin resistance in overweight adults, but no trial shows hard clinical outcomes. It is sold lawfully as a dietary supplement in the United States, is not prohibited by WADA, and has not been reviewed as a drug by FDA.", "mechanism": "Carnosine buffers hydrogen ions inside muscle fibers during intense exercise, chelates transition metals such as copper and zinc, scavenges reactive oxygen species, and forms adducts with reactive aldehydes and sugars, which reduces advanced glycation and lipoxidation end products. It also modulates calcium handling in muscle. The enzyme carnosinase breaks it down rapidly in human blood, so oral carnosine raises tissue levels less efficiently than its precursor beta-alanine. These mechanisms are well described in the 2013 Physiological Reviews article.", "evidence_grade": "human_rct", "evidence_summary": "Several small randomized trials and meta-analyses. De Courten et al. 2016 randomized 30 overweight, non-diabetic adults to carnosine 2 g per day or placebo for 12 weeks: insulin resistance and 2 hour glucose worsened on placebo but not on carnosine, with no weight change. Menon et al. 2020 pooled randomized trials of histidine containing dipeptides and found reductions in fasting glucose, HbA1c, and waist circumference, mostly in people with metabolic disease. Saadati et al. 2024 pooled trials and found reductions in some inflammatory and oxidative stress markers. Beta-alanine supplementation raises muscle carnosine by 40% to 60% and modestly improves high intensity exercise capacity (Hill 2007). No trial has measured cardiovascular events, diabetes incidence, or mortality.", "human_evidence": "De Courten 2016: 30 overweight or obese adults without diabetes, 2 g carnosine daily versus placebo for 12 weeks; carnosine prevented the rise in fasting insulin, insulin resistance, and 2 hour glucose seen on placebo, with no change in weight or body fat. Menon 2020 meta-analysis of randomized trials of carnosine and related dipeptides: significant reductions in fasting glucose, HbA1c, and waist circumference, with no consistent effect on lipids or blood pressure. Saadati 2024 meta-analysis: reductions in tumor necrosis factor alpha and malondialdehyde across pooled trials. Hill 2007: 4 weeks of beta-alanine (up to 6.4 g per day) raised muscle carnosine by about 60% and improved total work done in a cycling capacity test.", "animal_evidence": "Rodent studies show carnosine reduces advanced glycation end products, protects against diabetic kidney and vascular changes, improves outcomes after ischemic brain injury, and, in some strains, extends life span, as reviewed by Boldyrev et al. 2013. Rodents have far less serum carnosinase than humans, so oral carnosine reaches tissues more effectively in animals than in people.", "conditions": [ "longevity", "type-2-diabetes", "obesity" ], "literature_dosing": "Randomized trials used oral carnosine 2 g per day for 12 weeks (De Courten 2016) and 0.5 to 2 g per day across pooled trials (Menon 2020). Beta-alanine trials used 3.2 to 6.4 g per day for 4 weeks to raise muscle carnosine (Hill 2007).", "routes": [ "Oral capsule or powder (dietary supplement)", "Oral beta-alanine as a precursor", "Eye drops (N-acetylcarnosine, marketed without strong evidence)" ], "side_effects": [ "Generally well tolerated in trials at 2 g per day", "Mild gastrointestinal upset reported occasionally", "Beta-alanine (the precursor) causes dose dependent tingling (paresthesia)", "Long term safety beyond several months has not been formally studied" ], "interactions": [ "No clinically significant interactions documented", "Theoretical additive glucose lowering with diabetes medications, given trial effects on glucose (monitor)", "Carnosine chelates copper and zinc; separating it from mineral supplements is a theoretical precaution" ], "contraindications": [ "Known hypersensitivity to carnosine or beta-alanine", "Pregnancy and breastfeeding (no data at supplemental doses)" ], "wada_status": "not_prohibited", "fda_status": "unscheduled", "compounding_status": "Carnosine is regulated as a dietary supplement under the Dietary Supplement Health and Education Act and is not an FDA approved drug; it has not been reviewed by FDA as a drug and has no Pharmacy Compounding Advisory Committee history. Oral products are lawfully sold over the counter. Injectable carnosine is not an approved product, and any injectable version would need a 503A bulks listing to be compounded lawfully.", "typical_cost": "Roughly 15 to 40 USD per month for oral carnosine at 1 to 2 g per day; beta-alanine is roughly 10 to 25 USD per month.", "access_path": [ "Over the counter dietary supplement, no prescription needed.", "Beta-alanine supplements as a precursor for raising muscle carnosine." ], "faqs": [ { "q": "Is carnosine legal and safe to take?", "a": "Yes. Carnosine is a naturally occurring dipeptide sold lawfully as a dietary supplement in the United States. Randomized trials at 2 g per day for 12 weeks reported no serious adverse effects, and the main complaint with its precursor beta-alanine is harmless tingling. It is not an FDA approved drug and no long term safety trial exists.", "source_ids": [ "de-courten-2016", "hill-2007" ] }, { "q": "Does carnosine help with blood sugar or diabetes?", "a": "Modestly, in small trials. In 30 overweight adults, 2 g per day for 12 weeks prevented the worsening of insulin resistance and 2 hour glucose seen on placebo. A 2020 meta-analysis of randomized trials found reductions in fasting glucose, HbA1c, and waist circumference. No trial has shown fewer diabetes diagnoses or complications, so it is not a substitute for standard treatment.", "source_ids": [ "de-courten-2016", "menon-2020" ] }, { "q": "Is carnosine an anti-aging supplement?", "a": "The rationale is that carnosine blocks glycation and oxidative damage, and rodent studies show reduced advanced glycation end products and, in some strains, longer life. In humans, trials show lower markers of inflammation and oxidative stress but no evidence of slower aging, and because human blood breaks carnosine down quickly, oral doses reach tissues less efficiently than in rodents.", "source_ids": [ "boldyrev-2013", "saadati-2024" ] }, { "q": "What are the side effects of carnosine?", "a": "Few. Trials at 2 g per day reported occasional mild stomach upset and nothing serious. Beta-alanine, which people take to raise muscle carnosine, causes dose dependent tingling of the skin that fades within an hour and is not harmful. Safety beyond a few months of use has not been formally studied.", "source_ids": [ "de-courten-2016", "hill-2007" ] }, { "q": "How is carnosine taken?", "a": "As oral capsules or powder, typically 1 to 2 g per day in trials. Because serum carnosinase degrades it quickly, athletes usually take beta-alanine (3.2 to 6.4 g per day for several weeks) instead, which raised muscle carnosine by about 60% in a 2007 study. Injectable carnosine has no established role.", "source_ids": [ "menon-2020", "hill-2007" ] }, { "q": "Is carnosine banned by WADA?", "a": "No. Carnosine and beta-alanine are not listed in any section of the WADA Prohibited List as of 2026. Beta-alanine is widely used by athletes as a lawful buffering supplement. As with all supplements, contamination is the practical doping risk, so third party tested products are advisable.", "source_ids": [ "wada-list", "hill-2007" ] }, { "q": "Carnosine vs beta-alanine: which should I take?", "a": "For raising muscle carnosine and buffering exercise acid, beta-alanine is better supported because oral carnosine is largely broken down in the blood before reaching muscle. For the glycemic and waist effects seen in metabolic trials, the studies used carnosine itself at 0.5 to 2 g per day. They are not interchangeable, and neither has outcome data beyond biomarkers and exercise tests.", "source_ids": [ "hill-2007", "menon-2020", "boldyrev-2013" ] } ], "studies": [ { "pmid": "27040154", "title": "Effects of carnosine supplementation on glucose metabolism: pilot clinical trial", "year": 2016, "design": "Randomized, double blind, placebo controlled pilot trial, 12 weeks", "n": 30, "population": "Overweight or obese adults without diabetes", "outcome": "Carnosine 2 g per day prevented the rise in fasting insulin, insulin resistance, and 2 hour glucose seen on placebo; no change in body weight", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27040154/" }, { "pmid": "31828942", "title": "Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials", "year": 2020, "design": "Systematic review and meta-analysis of randomized trials", "population": "Adults in randomized trials of carnosine, anserine, or beta-alanine", "outcome": "Significant reductions in fasting glucose, HbA1c, and waist circumference; no consistent effect on lipids or blood pressure", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31828942/" }, { "pmid": "38086332", "title": "Effects of carnosine and histidine-containing dipeptides on biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis", "year": 2024, "design": "Systematic review and meta-analysis of randomized trials", "population": "Adults in randomized trials of carnosine and related dipeptides", "outcome": "Reductions in tumor necrosis factor alpha and malondialdehyde; other markers not consistently changed", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/38086332/" }, { "pmid": "16868650", "title": "Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity", "year": 2007, "design": "Randomized, placebo controlled supplementation trial, 4 to 10 weeks", "n": 25, "population": "Physically active men", "outcome": "Beta-alanine raised muscle carnosine by about 60% at 4 weeks and 80% at 10 weeks and increased total work done in a cycling capacity test", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16868650/" } ], "sources": [ { "id": "de-courten-2016", "type": "pubmed", "title": "de Courten B et al. Effects of carnosine supplementation on glucose metabolism: pilot clinical trial. Obesity (Silver Spring) 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27040154/", "pmid": "27040154", "year": 2016 }, { "id": "menon-2020", "type": "pubmed", "title": "Menon K et al. Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials. Obes Rev 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31828942/", "pmid": "31828942", "year": 2020 }, { "id": "saadati-2024", "type": "pubmed", "title": "Saadati S et al. Effects of carnosine and histidine-containing dipeptides on biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis. Nutr Rev 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38086332/", "pmid": "38086332", "year": 2024 }, { "id": "hill-2007", "type": "pubmed", "title": "Hill CA et al. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 2007", "url": "https://pubmed.ncbi.nlm.nih.gov/16868650/", "pmid": "16868650", "year": 2007 }, { "id": "boldyrev-2013", "type": "pubmed", "title": "Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/24137022/", "pmid": "24137022", "year": 2013 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "glutathione", "nad-plus", "ghk-cu" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Carnosine supplements: benefits, evidence, and safety" } }, { "slug": "glutathione", "name": "Glutathione", "aliases": [ "GSH", "L-glutathione reduced", "Gamma-glutamyl-cysteinyl-glycine", "IV glutathione", "Liposomal glutathione" ], "class": "Naturally occurring tripeptide (glutamate, cysteine, glycine), the main intracellular antioxidant; sold as oral supplements and compounded injections", "one_liner": "The body's main antioxidant tripeptide; one RCT shows oral doses raise body stores, clinical benefit is unproven, and IV use is compounded pending an FDA rule.", "summary": "Glutathione is a tripeptide made in every cell that neutralizes reactive oxygen species and detoxifies drugs and metabolites. A 6 month randomized trial of 54 adults found oral glutathione at 250 or 1,000 mg per day raised blood and cell glutathione stores by up to about 30%, while a 4 week trial found no change in oxidative stress markers, and no trial shows a clinical benefit for skin lightening, detoxification, or aging. Intravenous glutathione is compounded and given in clinics; the substance was nominated for the FDA 503A bulks list and has no final determination, and FDA has warned about compounded glutathione products with excessive endotoxin.", "mechanism": "Glutathione donates electrons to neutralize peroxides through glutathione peroxidases, regenerates vitamins C and E, and conjugates with electrophilic toxins through glutathione S-transferases for excretion. Cysteine availability limits its synthesis, which is why N-acetylcysteine and glycine are used as precursors. Oral glutathione was long thought to be fully digested, but the 2015 trial showed body stores rise with sustained dosing. Proposed skin lightening works by shifting melanin synthesis toward lighter pheomelanin, a mechanism shown in cells with weak human support.", "evidence_grade": "human_rct", "evidence_summary": "Two randomized trials address the basic question of whether oral glutathione raises levels. Richie et al. 2015 (54 healthy adults, 250 or 1,000 mg per day for 6 months) found dose dependent increases in glutathione in blood, red cells, lymphocytes, and buccal cells (up to about 30% to 35% at the high dose) and increased natural killer cell activity, with levels returning to baseline after a 1 month washout. Allen and Bradley 2011 (40 healthy adults, 500 mg twice daily for 4 weeks) found no change in oxidative stress biomarkers. No randomized trial demonstrates a clinical outcome for intravenous glutathione, and skin lightening claims rest on small, short trials with inconsistent results.", "human_evidence": "Richie 2015: 54 healthy non-smoking adults randomized to placebo, 250 mg, or 1,000 mg oral glutathione daily for 6 months; body stores rose in a dose and time dependent manner, with whole blood glutathione up about 30% and lymphocyte glutathione up about 35% at 1,000 mg, and natural killer cytotoxicity doubled at 3 months in the high dose group. Allen 2011: 40 healthy adults randomized to 500 mg twice daily or placebo for 4 weeks; no significant change in glutathione levels or oxidative stress markers. No published randomized trial of intravenous glutathione for any common clinic indication was identified.", "animal_evidence": "Rodent studies show glutathione depletion sensitizes tissues to oxidative and drug induced injury (the basis for N-acetylcysteine in acetaminophen overdose) and that glutathione or precursor supplementation protects liver, kidney, and lung in toxicity models. Animal data do not address the aging or cosmetic uses marketed to consumers.", "conditions": [ "longevity", "skin-aging" ], "literature_dosing": "Randomized trials used oral glutathione 250 mg or 1,000 mg per day for 6 months (Richie 2015) and 500 mg twice daily for 4 weeks (Allen 2011). No randomized trial establishes an intravenous or injectable dose for any clinic indication; IV doses used in clinics vary widely and are not evidence based.", "routes": [ "Oral capsule, liposomal, or sublingual (dietary supplement)", "Intravenous infusion or push (compounded, clinics)", "Intramuscular or subcutaneous injection (compounded)", "Inhaled (nebulized, studied in cystic fibrosis)" ], "side_effects": [ "Oral: generally well tolerated; mild bloating or cramps reported occasionally", "IV: flushing, nausea, and rare allergic reactions; asthma exacerbation reported with inhaled glutathione", "Compounded injectable products have been recalled or warned about for excessive endotoxin, causing fever and chills after infusion", "Long term safety of high dose supplementation and of skin lightening use is not established" ], "interactions": [ "No clinically significant interactions documented for oral use", "Theoretical reduction in efficacy of some chemotherapy agents that act through oxidative stress; oncology patients should not use it without their oncologist's input", "May interact with the metabolism of drugs that rely on glutathione conjugation (theoretical)" ], "contraindications": [ "Active cancer treatment without oncologist approval (theoretical interference with therapy)", "Asthma for inhaled forms", "Pregnancy and breastfeeding for injectable forms (no data)", "Known hypersensitivity to glutathione or product excipients" ], "wada_status": "not_prohibited", "fda_status": "under_review", "compounding_status": "Glutathione is not an FDA approved drug. Oral glutathione is sold lawfully as a dietary supplement. Injectable glutathione is compounded from a bulk substance that was nominated for the FDA 503A bulks list and appears on the nominated substances lists pending a final determination; compounding continues under FDA's interim enforcement policy where state boards permit. FDA has issued warnings about compounded glutathione products containing high levels of endotoxin and about glutathione injections marketed for skin lightening, which is not an approved use.", "typical_cost": "Compounded injectable glutathione through licensed telehealth programs runs about 75 to 100 USD per month; a glutathione injection or IV add-on at an IV clinic is about 35 to 50 USD. Oral supplements are sold over the counter. Prices checked 2026-09-22 on published provider and pharmacy price pages.", "access_path": [ "Over the counter dietary supplement, no prescription needed.", "Prescription from a licensed provider filled by a 503A compounding pharmacy for injectable glutathione, where the state board permits it.", "Clinic or telehealth programs offering IV or injectable glutathione." ], "faqs": [ { "q": "Is glutathione legal, and is it FDA approved?", "a": "Oral glutathione is a lawful dietary supplement. Injectable glutathione is not FDA approved; it is compounded from a bulk substance that has been nominated for the FDA 503A bulks list without a final rule, so clinics offer it under interim enforcement discretion. FDA has warned about compounded products with high endotoxin and about marketing injections for skin lightening.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa" ] }, { "q": "Does oral glutathione actually get absorbed?", "a": "Yes, with sustained dosing. In a 6 month randomized trial of 54 adults, 1,000 mg per day raised whole blood glutathione by about 30% and lymphocyte glutathione by about 35%, and levels fell back after stopping. A shorter 4 week trial at 1,000 mg per day found no change, so time and dose matter.", "source_ids": [ "richie-2015", "allen-2011" ] }, { "q": "Does glutathione work for skin whitening?", "a": "The evidence is weak. The mechanism is shown in cells, and a few small short trials of oral or topical glutathione reported slight lightening that was inconsistent and not durable. No randomized trial supports intravenous glutathione for skin lightening, FDA has warned against marketing injections for that purpose, and the practice is unregulated in many clinics.", "source_ids": [ "fda-compounding-qa", "richie-2015" ] }, { "q": "What are the side effects of glutathione?", "a": "Oral glutathione was well tolerated over 6 months in the largest trial, with occasional mild stomach complaints. IV glutathione can cause flushing, nausea, and rarely allergic reactions, and compounded products contaminated with endotoxin have caused fever and chills after infusion. Inhaled glutathione can trigger bronchospasm in people with asthma.", "source_ids": [ "richie-2015", "fda-compounding-qa" ] }, { "q": "How is glutathione taken?", "a": "Trials used oral doses of 250 to 1,000 mg per day, taken daily for months. Clinics give it intravenously or by injection at doses that vary widely and have not been tested in randomized trials. Precursors such as N-acetylcysteine and glycine are another way to raise glutathione that has its own evidence base.", "source_ids": [ "richie-2015", "allen-2011" ] }, { "q": "How much does glutathione cost?", "a": "Compounded injectable glutathione through licensed telehealth programs is about 75 to 100 USD per month, and a glutathione injection or IV add-on at an IV clinic is about 35 to 50 USD. Oral supplements are sold over the counter. Prices were checked on 2026-09-22 and change often.", "source_ids": [ "price-telehealth-glutathione-a", "price-telehealth-glutathione-b", "price-iv-clinic", "fda-503a-bulks" ] }, { "q": "Is glutathione banned by WADA?", "a": "No. Glutathione is a naturally occurring antioxidant and is not listed in any section of the WADA Prohibited List as of 2026. Athletes should note that IV infusions above 100 mL in a 12 hour period are prohibited under section M2 regardless of the substance, unless given in a hospital setting or with an exemption.", "source_ids": [ "wada-list" ] }, { "q": "Glutathione vs NAC: which raises glutathione better?", "a": "Both work. N-acetylcysteine supplies cysteine, the rate limiting building block, and has decades of clinical use. Oral glutathione itself raised body stores by about 30% over 6 months in a randomized trial. Head to head comparisons are lacking, and neither has been shown to improve aging or skin outcomes in a rigorous trial.", "source_ids": [ "richie-2015", "allen-2011" ] } ], "studies": [ { "pmid": "24791752", "title": "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione", "year": 2015, "design": "Randomized, double blind, placebo controlled trial, 6 months plus 1 month washout", "n": 54, "population": "Healthy non-smoking adults", "outcome": "Dose dependent increases in glutathione in whole blood, red cells, lymphocytes, and buccal cells (up to about 30% to 35% at 1,000 mg per day); natural killer cell activity doubled at 3 months in the high dose group", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/24791752/" }, { "pmid": "21875351", "title": "Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers", "year": 2011, "design": "Randomized, double blind, placebo controlled trial, 4 weeks", "n": 40, "population": "Healthy adults", "outcome": "No significant change in glutathione levels or oxidative stress biomarkers with 500 mg twice daily", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/21875351/" } ], "sources": [ { "id": "richie-2015", "type": "pubmed", "title": "Richie JP Jr et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/24791752/", "pmid": "24791752", "year": 2015 }, { "id": "allen-2011", "type": "pubmed", "title": "Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21875351/", "pmid": "21875351", "year": 2011 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers (including risks of compounded drugs and enforcement policy for nominated bulk substances)", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (including section M2 on intravenous infusions)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-telehealth-glutathione-a", "type": "other", "title": "Licensed telehealth provider price page for compounded glutathione injections, accessed 2026-09-22", "url": "https://trynovamd.com/glutathione" }, { "id": "price-telehealth-glutathione-b", "type": "other", "title": "Second licensed telehealth provider price page for compounded glutathione injections, accessed 2026-09-22", "url": "https://joinamble.com/glutathione" }, { "id": "price-iv-clinic", "type": "other", "title": "Registered nurse staffed IV clinic published price menu (NAD+ and glutathione), accessed 2026-09-22", "url": "https://hydrateivbar.com/pricing/" } ], "related": [ "nad-plus", "carnosine", "ghk-cu" ], "cluster": "longevity", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Glutathione: oral vs IV evidence and legal status" } }, { "slug": "semax", "name": "Semax", "aliases": [ "Met-Glu-His-Phe-Pro-Gly-Pro", "ACTH(4-7)-Pro-Gly-Pro", "Semax 0.1% and 1% nasal drops", "N-acetyl Semax and NA-Semax amidate (unstudied analogs)", "Semax peptide", "Semax nasal spray", "Semax nasal drops" ], "class": "Synthetic heptapeptide analog of ACTH fragment 4-10 (Met-Glu-His-Phe-Pro-Gly-Pro), a melanocortin derived nootropic and neuroprotective peptide", "one_liner": "Nasal peptide registered in Russia; rodent brain growth factor data and open label Russian stroke trials; not FDA approved; recommended for compounding in 2026.", "summary": "Semax is a seven amino acid fragment of the stress hormone ACTH, modified to have no hormonal activity, developed in Moscow and registered in Russia as nasal drops for stroke, cognitive impairment, and optic nerve disease. Rodent studies show it raises BDNF (a protein that supports nerve cell growth) and its receptor in the hippocampus, the brain's memory center, and Russian clinical studies from the 1990s onward report better recovery after ischemic stroke (stroke from a blocked artery), but those trials are open label (everyone knew who was treated), published in Russian, and not independently replicated. FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in April 2026 and the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) recommended it for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) in July 2026; no final rule has been published.", "mechanism": "Semax is derived from ACTH(4-10) with a C-terminal Pro-Gly-Pro that protects it from breakdown. It does not stimulate cortisol release. In rat hippocampus a single intranasal dose increased BDNF protein and trkB receptor expression within hours, and rodent work also shows effects on the serotonergic and dopaminergic systems, reduced nitric oxide production after ischemia, and increased expression of neurotrophic and immune genes. Intranasal delivery is proposed to reach the brain along olfactory pathways. Human mechanistic data are limited.", "evidence_grade": "human_observational", "evidence_summary": "Human evidence consists of Russian clinical trials that are open label or poorly described, published in Russian language journals. Gusev et al. 1997 reported faster neurological recovery and lower mortality in acute hemispheric ischemic stroke patients given intranasal semax alongside standard care compared with controls. Gusev et al. 2005 reported fewer exacerbations in chronic cerebrovascular insufficiency, and Gusev et al. 2018 reported benefits at several stages of ischemic stroke. None used a placebo controlled double blind design described in an indexed English language report, and none have independent replication. Animal data on BDNF induction are more rigorous. PeptideAgent grades the evidence human observational.", "human_evidence": "Gusev 1997: patients in the acute period of hemispheric ischemic stroke received intranasal semax (12 to 18 mg per day) with standard therapy; the authors report faster regression of neurological deficit and improved EEG parameters versus standard therapy alone. Gusev 2005: patients with chronic cerebrovascular insufficiency treated with semax courses had fewer exacerbations over follow up. Gusev 2018: an analysis across stages of ischemic stroke reporting improved functional outcomes. These are open comparative studies without blinding or placebo, from the developing research group.", "animal_evidence": "Dolotov et al. 2006: intranasal semax in rats increased hippocampal BDNF protein about 1.4 fold and trkB expression within hours of a single dose. Other rodent studies from the Institute of Molecular Genetics report reduced infarct volume after focal ischemia, changes in expression of hundreds of genes involved in inflammation and neurotransmission, and improved learning in behavioral tests.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Russian stroke studies used intranasal semax 12 to 18 mg per day (1% solution) for 5 to 10 days in acute ischemic stroke, and lower doses of the 0.1% solution (roughly 0.2 to 2 mg per day) for cognitive and asthenic indications, according to Russian labeling and open label reports. No dose finding trial has been published in an indexed English language journal.", "routes": [ "Intranasal drops (Russian product and most sold forms)", "Subcutaneous injection (as sold, no published human data)" ], "side_effects": [ "No systematic safety data from blinded trials", "Nasal irritation reported with intranasal use", "Anxiety, irritability, or insomnia reported anecdotally with higher doses", "Hair loss reported anecdotally without study confirmation", "Long term safety unknown" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive effects with other serotonergic or dopaminergic agents given rodent monoamine data (not tested)" ], "contraindications": [ "Russian labeling lists acute psychosis, anxiety disorders with agitation, pregnancy, and breastfeeding", "Children (no data outside Russian pediatric reports)", "Competitive athletes should confirm status with their anti-doping organization" ], "wada_status": "unclear", "fda_status": "under_review", "compounding_status": "Semax was placed on the FDA 503A Category 2 list (substances with significant safety risks) in 2023 and removed from it on April 15, 2026. On July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee recommended adding semax to the 503A bulks list. As of the last verification date FDA has not published a final rule, so compounding pharmacies and state boards vary in whether they will fill it. It is not an FDA approved drug and is not eligible for 503B outsourcing. It is a registered prescription drug in Russia.", "typical_cost": "No lawful compounded price: Semax is not on the 503A bulks list, and PCAC's July 2026 recommendation is advisory until FDA publishes a final rule. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful compounded access path yet: PCAC recommended it for the 503A bulks list in July 2026, but until FDA publishes a final rule a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product; registered prescription drug in Russia.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is semax peptide used for?", "a": "Semax is a synthetic seven amino acid fragment of the stress hormone ACTH. In Russia it is a registered prescription drug given as nasal drops for ischemic stroke (stroke from a blocked artery) and chronic cerebrovascular disease (long term poor blood flow to the brain). In the United States it is not FDA approved and is marketed mainly as a nootropic (a supposed focus and memory enhancer), a use no controlled trial has tested.", "source_ids": [ "gusev-1997", "gusev-2005", "fda-503a-bulks" ] }, { "q": "Is semax legal in the United States?", "a": "It is not an FDA approved drug, but possessing it is not a crime. FDA removed semax from its 503A Category 2 list on April 15, 2026, and the Pharmacy Compounding Advisory Committee voted in July 2026 to recommend it for the 503A bulks list. Until FDA publishes a final rule it is not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. It is a registered prescription drug in Russia.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Semax benefits: what does the evidence show?", "a": "The claimed benefits rest on two kinds of evidence. In rats, a single intranasal dose raised hippocampal BDNF and its trkB receptor within hours, which is the basis for the cognitive claims. In people, Russian open label studies report faster recovery after ischemic stroke and fewer exacerbations of chronic cerebrovascular disease. There is no blinded placebo controlled trial in an indexed English language journal and no study in healthy adults, so benefits for focus or memory are unproven. PeptideAgent grades the evidence human observational.", "source_ids": [ "dolotov-2006", "gusev-1997", "gusev-2005" ] }, { "q": "Does semax help after a stroke?", "a": "Russian trials say yes: Gusev and colleagues reported faster neurological recovery in acute hemispheric ischemic stroke in 1997 and benefits across stroke stages in 2018. These studies were open label, compared semax plus standard care against standard care alone, and came from the group that developed the drug, so the effect has not been confirmed by an independent blinded trial.", "source_ids": [ "gusev-1997", "gusev-2018" ] }, { "q": "How does semax work, and what is its half-life?", "a": "Semax is built from the ACTH(4-10) sequence with a Pro-Gly-Pro tail added to slow its breakdown. In rats it increases BDNF and its trkB receptor in the hippocampus, a growth factor pathway tied to learning. No human half-life has been published. In a rat study using labeled semax given into the nose, the peptide reached the brain within 2 minutes and was rapidly broken down by enzymes, with the Pro-Gly-Pro fragment making up most of what remained.", "source_ids": [ "dolotov-2006", "shevchenko-2006" ] }, { "q": "What are the side effects of semax?", "a": "No blinded safety trial exists. Nasal irritation is the most common complaint with drops. Anecdotal reports mention anxiety, irritability, insomnia, and hair thinning at higher doses, none confirmed by study. Russian labeling advises against use in acute psychosis and agitated anxiety states and in pregnancy.", "source_ids": [ "gusev-2005", "gusev-2018" ] }, { "q": "How is semax taken?", "a": "As nasal drops, the form registered in Russia in 0.1% and 1% strengths and the route used in the published human studies. Injectable versions are sold but have no published human data. Semax is not an approved drug in the United States, so there is no US labeled dose. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "gusev-1997", "gusev-2005" ] }, { "q": "Is semax banned by WADA?", "a": "Unclear. Semax is not named on the WADA Prohibited List, and because it is an approved drug in Russia it does not automatically fall under section S0 for non-approved substances. It is an ACTH fragment without corticotropic activity, but athletes should confirm with their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "Semax vs selank: what is the difference?", "a": "Both are Russian nasal peptides from the same research tradition. Semax is an ACTH fragment marketed for stroke recovery and cognition with rodent BDNF data; selank is a tuftsin analog marketed for anxiety with small Russian comparative trials against benzodiazepines. Semax was recommended for the FDA 503A bulks list in July 2026; selank was not part of that recommendation. Neither has an independent blinded trial.", "source_ids": [ "dolotov-2006", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "16996037", "title": "Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus", "year": 2006, "design": "Rat study of intranasal peptide administration", "population": "Rats", "outcome": "Single intranasal dose increased hippocampal BDNF protein and trkB expression within hours", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/16996037/" }, { "pmid": "11517472", "title": "Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)", "year": 1997, "design": "Open comparative clinical study, Russian language", "population": "Adults in the acute period of hemispheric ischemic stroke", "outcome": "Faster regression of neurological deficit and improved EEG measures with intranasal semax added to standard therapy; not blinded or placebo controlled", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/11517472/" }, { "pmid": "15792140", "title": "Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency", "year": 2005, "design": "Open comparative clinical study, Russian language", "population": "Adults with chronic cerebrovascular insufficiency", "outcome": "Fewer exacerbations and slower progression reported with semax courses; not blinded", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/15792140/" }, { "pmid": "29798983", "title": "The efficacy of semax in the treatment of patients at different stages of ischemic stroke", "year": 2018, "design": "Open comparative clinical study, Russian language", "population": "Adults at acute, early recovery, and late recovery stages of ischemic stroke", "outcome": "Improved functional recovery reported with semax across stages; not blinded or placebo controlled", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/29798983/" } ], "sources": [ { "id": "dolotov-2006", "type": "pubmed", "title": "Dolotov OV et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16996037/", "pmid": "16996037", "year": 2006 }, { "id": "gusev-1997", "type": "pubmed", "title": "Gusev EI et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zh Nevrol Psikhiatr Im S S Korsakova 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/11517472/", "pmid": "11517472", "year": 1997 }, { "id": "gusev-2005", "type": "pubmed", "title": "Gusev EI et al. Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zh Nevrol Psikhiatr Im S S Korsakova 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15792140/", "pmid": "15792140", "year": 2005 }, { "id": "gusev-2018", "type": "pubmed", "title": "Gusev EI et al. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29798983/", "pmid": "29798983", "year": 2018 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "shevchenko-2006", "type": "pubmed", "title": "Shevchenko KV et al. Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration. Bioorg Khim 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16523722/", "pmid": "16523722", "year": 2006 } ], "related": [ "selank", "cerebrolysin", "noopept", "p21" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Semax peptide: benefits, side effects, and legal status", "description": "What semax peptide is used for, what Russian stroke trials and rat BDNF studies show, side effects, how it works, and its 2026 FDA status.", "h1": "Semax peptide", "headings": { "evidence": "Semax benefits: what the evidence shows", "safety": "Semax side effects" } } }, { "slug": "selank", "name": "Selank", "aliases": [ "Thr-Lys-Pro-Arg-Pro-Gly-Pro", "Tuftsin-Pro-Gly-Pro", "Selank 0.15% nasal drops", "N-acetyl Selank and NA-Selank amidate (unstudied analogs)", "Selank peptide", "Selank nasal spray", "Selank nasal drops" ], "class": "Synthetic heptapeptide analog of the immune tetrapeptide tuftsin (Thr-Lys-Pro-Arg) extended with Pro-Gly-Pro, a Russian anxiolytic peptide", "one_liner": "Anti-anxiety nasal peptide registered in Russia, with small open label trials against a benzodiazepine; not FDA approved and not on FDA advisers' 2026 list.", "summary": "Selank is a seven amino acid synthetic analog (modified version) of tuftsin, a natural immune signaling fragment, developed in Moscow and registered in Russia as nasal drops for anxiety and asthenia (chronic fatigue and weakness). Small Russian clinical studies report anxiolytic (anti-anxiety) effects comparable to the benzodiazepine phenazepam, a sedating anxiety drug, without sedation, and rodent studies suggest actions on GABA receptors (the brain's calming system), serotonin, and enkephalin breakdown, but no blinded placebo controlled trial (where no one knows who got the real drug) has been published in an indexed English language journal. It has never been approved by FDA, was placed on the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in 2023, is now listed by FDA as a withdrawn nomination (off Category 2 but not on the bulks list of ingredients pharmacies may use), and was not among the peptides the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) recommended in July 2026.", "mechanism": "Selank is built from tuftsin, a natural immune stimulating fragment of immunoglobulin G, with a C-terminal Pro-Gly-Pro added for stability. Proposed mechanisms from rodent and cell work include allosteric modulation of GABA-A receptors, inhibition of enkephalin degrading enzymes (raising endogenous opioid peptide levels), modulation of serotonin and brain derived neurotrophic factor expression, and changes in cytokine expression. A 2018 review summarizes these molecular findings; none has been confirmed in humans.", "evidence_grade": "human_observational", "evidence_summary": "Human evidence consists of small Russian clinical studies. Zozulya et al. 2008 reported reduced anxiety scores in patients with generalized anxiety disorder and neurasthenia treated with intranasal selank, with proposed effects on enkephalin metabolism. Medvedev et al. 2014 compared selank with phenazepam in anxiety disorders and reported similar anxiolytic effect with better tolerability, and Medvedev 2015 reported that adding selank optimized anxiety treatment. These studies are open or single blind, small, published in Russian, and from the developing research network; no independent blinded placebo controlled trial exists. Rodent studies support anxiolytic and nootropic effects.", "human_evidence": "Zozulya 2008: patients with generalized anxiety disorder or neurasthenia received intranasal selank; authors report reduced Hamilton anxiety scores and changes in serum enkephalin degrading activity. Medvedev 2014: comparative study of selank versus phenazepam in anxiety disorders reporting comparable reductions in anxiety with fewer sedative effects for selank. Medvedev 2015: report on optimizing anxiety treatment with selank added to standard regimens. None were double blind placebo controlled by indexed English language description.", "animal_evidence": "Rodent studies report reduced anxiety like behavior in elevated plus maze and open field tests, improved memory retention, and modulation of GABA-A receptor function and monoamine turnover. Vyunova et al. 2018 review the molecular pharmacology, including effects on GABAergic transmission and gene expression in brain regions.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Russian clinical studies used intranasal selank 0.15% solution at roughly 0.3 to 2.7 mg per day (2 to 3 drops per nostril, up to 3 times daily) for 10 to 14 days, according to Russian labeling and open label reports. No dose finding trial has been published in an indexed English language journal.", "routes": [ "Intranasal drops (Russian product and most sold forms)", "Subcutaneous injection (as sold, no published human data)" ], "side_effects": [ "No systematic safety data from blinded trials", "Nasal irritation with intranasal use", "Fatigue or drowsiness reported anecdotally despite claims of no sedation", "Long term safety unknown" ], "interactions": [ "No formal human interaction studies exist", "Theoretical additive effects with benzodiazepines, alcohol, and other GABAergic drugs given proposed GABA-A modulation (not tested)", "Theoretical interaction with opioids via enkephalinase inhibition (not tested)" ], "contraindications": [ "Russian labeling lists pregnancy, breastfeeding, and hypersensitivity", "Children (no indexed data)", "Competitive athletes should confirm status with their anti-doping organization" ], "wada_status": "unclear", "fda_status": "category_2_removed", "compounding_status": "Selank was placed on the FDA 503A Category 2 list (substances with significant safety risks) in 2023. The FDA Category 2 page current as of April 22, 2026 now lists selank acetate under bulk drug substances nominated but withdrawn, so it is no longer in Category 2, but it is not on the 503A bulks list and was not among the peptides the Pharmacy Compounding Advisory Committee recommended on July 23 to 24, 2026. With no active nomination and no listing, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not. It is not an FDA approved drug and is not eligible for 503B outsourcing. It is a registered prescription drug in Russia.", "typical_cost": "No lawful compounded price: selank is off 503A Category 2 but is not on the 503A bulks list and was not recommended by PCAC in July 2026. Advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Selank is off Category 2 but not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk.", "Not available as an FDA approved product; registered prescription drug in Russia.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is selank?", "a": "Selank is a synthetic seven amino acid peptide built from tuftsin, a natural immune signaling fragment, with a Pro-Gly-Pro tail added for stability. It was developed in Moscow and is registered in Russia as nasal drops for anxiety. It is not FDA approved, is not on the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), and was not among the peptides the FDA advisory committee recommended in July 2026, so there is no lawful US source.", "source_ids": [ "vyunova-2018", "zozulya-2008", "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Is selank legal in the United States?", "a": "It is not an FDA approved drug, but possessing it is not a crime. Selank was placed on FDA's 503A Category 2 list in 2023. FDA now lists it as a withdrawn nomination (off Category 2 but not on the 503A bulks list), and it was not among the peptides the advisory committee recommended for the bulks list in July 2026, so most US pharmacies will not compound it. It is a prescription drug in Russia.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Selank benefits: does it work for anxiety?", "a": "Small Russian studies say yes: a 2008 study reported lower anxiety scores in generalized anxiety disorder and neurasthenia, and a 2014 comparison found effects similar to the benzodiazepine phenazepam with less sedation. These were small, not placebo controlled, and not independently replicated, so the true effect size is unknown. PeptideAgent grades the evidence human observational.", "source_ids": [ "zozulya-2008", "medvedev-2014" ] }, { "q": "How does selank work?", "a": "The proposed mechanisms come from rodent and cell studies: modulation of GABA-A receptors, slower breakdown of enkephalins (the body's own opioid peptides), and changes in serotonin, BDNF, and immune gene expression. A 2008 clinical study linked its anti-anxiety effect to changes in enkephalin degrading activity in patients' blood. None of these mechanisms has been confirmed in controlled human research, and PeptideAgent found no indexed human pharmacokinetic study, so its half-life in people is unknown.", "source_ids": [ "vyunova-2018", "zozulya-2008" ] }, { "q": "What are the side effects of selank?", "a": "No blinded safety trial exists. Nasal irritation is the most common complaint with drops. Russian studies reported good tolerability compared with benzodiazepines, and anecdotal reports mention fatigue in some users. Long term safety has not been studied.", "source_ids": [ "medvedev-2014", "medvedev-2015" ] }, { "q": "How is selank taken?", "a": "As nasal drops, the form registered in Russia as a 0.15% solution and the route used in the published human studies. Injectable versions are sold but have no published human data. Selank is not an approved drug in the United States, so there is no US labeled dose. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "zozulya-2008", "medvedev-2015" ] }, { "q": "How much does selank cost?", "a": "There is no lawful compounded price: it is not on the 503A bulks list, and advertised clinic prices are not a comparable price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is selank banned by WADA?", "a": "Unclear. Selank is not named on the WADA Prohibited List, and because it is an approved drug in Russia it does not automatically fall under section S0 for non-approved substances. Athletes should confirm with their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "Selank vs semax: which is better?", "a": "They target different things. Selank is a tuftsin analog studied for anxiety with small Russian comparisons against benzodiazepines; semax is an ACTH fragment studied for stroke recovery and cognition with rodent BDNF data. Semax was recommended for the FDA 503A bulks list in July 2026 while selank was not. Neither has an independent blinded placebo controlled trial.", "source_ids": [ "vyunova-2018", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "18454096", "title": "Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia", "year": 2008, "design": "Open clinical study with biochemical measures, Russian language", "population": "Adults with generalized anxiety disorder or neurasthenia", "outcome": "Reduced anxiety scores with intranasal selank; changes in serum enkephalin degrading activity proposed as mechanism; not placebo controlled", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/18454096/" }, { "pmid": "25176261", "title": "A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders", "year": 2014, "design": "Comparative clinical study, Russian language", "population": "Adults with anxiety disorders", "outcome": "Anxiolytic effect comparable to phenazepam with better tolerability and less sedation reported for selank; not placebo controlled", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/25176261/" }, { "pmid": "26356395", "title": "Optimization of the treatment of anxiety disorders with selank", "year": 2015, "design": "Open clinical study, Russian language", "population": "Adults with anxiety disorders", "outcome": "Improved anxiety outcomes reported with selank added to treatment; not blinded", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26356395/" }, { "pmid": "30255741", "title": "Peptide-based anxiolytics: the molecular aspects of heptapeptide selank biological activity", "year": 2018, "design": "Narrative review of molecular and animal pharmacology", "population": "Rodent and cell studies", "outcome": "Summarizes GABA-A modulation, enkephalinase inhibition, monoamine effects, and gene expression changes underlying anxiolytic activity in animals", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/30255741/" } ], "sources": [ { "id": "zozulya-2008", "type": "pubmed", "title": "Zozulya AA et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zh Nevrol Psikhiatr Im S S Korsakova 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18454096/", "pmid": "18454096", "year": 2008 }, { "id": "medvedev-2014", "type": "pubmed", "title": "Medvedev VE et al. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders. Zh Nevrol Psikhiatr Im S S Korsakova 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25176261/", "pmid": "25176261", "year": 2014 }, { "id": "medvedev-2015", "type": "pubmed", "title": "Medvedev VE et al. Optimization of the treatment of anxiety disorders with selank. Zh Nevrol Psikhiatr Im S S Korsakova 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26356395/", "pmid": "26356395", "year": 2015 }, { "id": "vyunova-2018", "type": "pubmed", "title": "Vyunova TV et al. Peptide-based anxiolytics: the molecular aspects of heptapeptide selank biological activity. Protein Pept Lett 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30255741/", "pmid": "30255741", "year": 2018 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "semax", "dsip", "noopept" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Selank: evidence, side effects, and legal status", "description": "What selank is, what small Russian anxiety trials show, side effects, how it is thought to work, and why no US pharmacy can compound it in 2026.", "h1": "Selank peptide", "headings": { "evidence": "Selank benefits: what the evidence shows", "safety": "Selank side effects" } } }, { "slug": "dihexa", "name": "Dihexa", "aliases": [ "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide", "PNB-0408", "Dihexa peptide", "Angiotensin IV analog dihexa" ], "class": "Synthetic angiotensin IV derived oligopeptide (hexanoyl capped Tyr-Ile with an aminohexanoic amide tail), hepatocyte growth factor/c-Met potentiator", "one_liner": "Oral lab-made relative of the brain peptide angiotensin IV: rat memory data from one lab, a retracted mechanism paper, no human trials, no FDA approval.", "summary": "Dihexa is a small synthetic peptide derived from angiotensin IV, a breakdown product of the blood pressure hormone angiotensin II, and designed at Washington State University to cross the blood brain barrier (the filter that keeps most substances out of the brain) and promote synapse formation (new connections between nerve cells). Its entire evidence base is rat behavior and cell culture (cells grown in a dish) from the inventing laboratory: it reversed scopolamine induced memory deficits in rats in a 2013 paper that now carries an expression of concern (a journal warning about its reliability), and the 2014 paper proposing its hepatocyte growth factor mechanism was retracted in 2025. No human trial has been published, it is not FDA approved, and it is not available through any licensed channel in the United States.", "mechanism": "Dihexa was reported to bind hepatocyte growth factor (HGF) with high affinity and to potentiate signaling through the c-Met receptor, which in turn drives dendritic spine growth and synaptogenesis in cultured hippocampal neurons. The 2014 paper that established this mechanism was retracted by the journal in 2025, and the 2013 paper describing dihexa's design and rat memory effects carries a 2021 expression of concern, so the mechanism should be treated as unconfirmed. Dihexa is orally active and blood brain barrier permeant in rats according to the developers.", "evidence_grade": "animal_only", "evidence_summary": "One laboratory reports that dihexa reverses scopolamine induced deficits in the Morris water maze in rats, improves performance in aged rats, and increases hippocampal spine density in culture. Independent replication has not been published, the mechanism paper was retracted, and the design paper carries an expression of concern. No human pharmacokinetic, safety, or efficacy study exists as of the last verification date, so the grade is animal-only with a data integrity caveat.", "human_evidence": "No human study of any kind identified. No indexed human trial, case series, or safety report has been published. The developers' proposal to advance an angiotensin IV analog toward Alzheimer's disease trials has not resulted in a registered human trial with published results.", "animal_evidence": "McCoy et al. (2013) modified the N-terminal tripeptide of norleucine-1-angiotensin IV to produce dihexa, an orally active analog that reversed scopolamine induced deficits in Morris water maze performance in rats, improved spatial memory in aged rats, and increased hippocampal synaptogenesis. Benoist et al. (2014, retracted 2025) reported that dihexa's procognitive and synaptogenic effects in rats and cultured neurons depend on HGF/c-Met signaling. No toxicology study in animals has been published, and no group outside the inventing laboratory has replicated the memory findings.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Not established in human literature. Rat studies gave dihexa orally or by injection in scopolamine and aged rat memory models; no human pharmacokinetic or dose finding study has been published and no dose can be inferred from the animal work.", "routes": [ "Oral (rat studies; sold as capsules or powder)", "Intraperitoneal injection (rat studies)", "Transdermal and subcutaneous products exist without absorption data" ], "side_effects": [ "No human safety data of any kind published", "No animal toxicology study published", "Theoretical concern that potentiating HGF/c-Met signaling could promote tumor growth, because c-Met is an oncogene targeted by several cancer drugs (not tested for dihexa)", "Anecdotal reports of headache and fatigue are unverified" ], "interactions": [ "No formal interaction studies exist", "Theoretical opposition to c-Met inhibitors used in oncology (for example capmatinib, tepotinib, crizotinib), since dihexa is proposed to activate the same receptor", "Theoretical interaction with angiotensin system drugs given its angiotensin IV origin (not tested)" ], "contraindications": [ "Active cancer or history of cancer (c-Met is a well established oncogene, and dihexa is proposed to potentiate its signaling)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Dihexa has never been reviewed or approved by FDA for any use. It was named on the FDA 503A Category 2 list (substances with significant safety risks) in 2023. The FDA Category 2 page current as of April 22, 2026 now lists dihexa acetate under bulk drug substances nominated but withdrawn, so it is no longer in Category 2, but it is not on the 503A bulks list and was not among the peptides the Pharmacy Compounding Advisory Committee recommended on July 23 to 24, 2026. With no active nomination and no listing, a 503A pharmacy has no lawful basis to compound it. It is not eligible for 503B outsourcing and no licensed compounding pathway has been identified.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available for human use in the United States: no FDA approved product and no identified compounding pathway.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is dihexa?", "a": "Dihexa is a small synthetic peptide derived from angiotensin IV, a breakdown product of the blood pressure hormone angiotensin II, designed at Washington State University to cross the blood brain barrier (the filter that keeps most substances out of the brain) and promote new synapse formation (connections between nerve cells). It is marketed as a nootropic (a supposed memory or focus enhancer), but all of its evidence comes from rats and cell culture (cells grown in a dish) in the inventing laboratory, the paper proposing its mechanism was retracted in 2025, and it has never been tested in people or approved by FDA.", "source_ids": [ "mccoy-2013", "benoist-2014-retracted" ] }, { "q": "Is dihexa legal in the United States?", "a": "It is not an FDA approved drug and has never been reviewed by FDA. It was named on the FDA 503A Category 2 list in 2023; FDA now lists it as a withdrawn nomination (off Category 2 but not on the 503A bulks list), and it was not among the peptides the advisory committee recommended for the 503A bulks list in July 2026, so pharmacies have no basis to compound it. Possessing it is not a crime, but no licensed provider or pharmacy can lawfully supply it for human use, and research chemical products are not lawful for human consumption.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does dihexa work for memory or Alzheimer's disease?", "a": "In rats, the inventing laboratory reported that dihexa reversed scopolamine induced memory deficits and improved spatial memory in aged animals. In humans, there is no evidence at all: no trial, case series, or safety study has been published. The 2014 paper that explained how dihexa is supposed to work was retracted in 2025 and the 2013 design paper carries an expression of concern, so even the animal claims should be read cautiously. PeptideAgent grades the evidence animal-only.", "source_ids": [ "mccoy-2013", "benoist-2014-retracted" ] }, { "q": "What are the side effects of dihexa?", "a": "Nobody knows, because no human safety data and no animal toxicology study have been published. The most discussed theoretical risk is cancer: dihexa is proposed to potentiate the HGF/c-Met pathway, and c-Met is an oncogene that several approved cancer drugs are designed to block. Reports of headache or fatigue from users are anecdotal and unverified.", "source_ids": [ "benoist-2014-retracted", "wright-harding-2015" ] }, { "q": "Why was the dihexa mechanism paper retracted?", "a": "The 2014 Journal of Pharmacology and Experimental Therapeutics paper by Benoist and colleagues, which reported that dihexa binds hepatocyte growth factor and acts through c-Met, received an expression of concern from the journal in 2021 and was retracted in April 2025. The companion 2013 paper describing dihexa's synthesis and rat memory effects received an expression of concern at the same time. PeptideAgent lists both so readers can see the record, but treats the mechanism as unconfirmed.", "source_ids": [ "benoist-2014-retracted", "mccoy-2013" ] }, { "q": "How is dihexa taken?", "a": "In the rat studies it was given orally or by injection. Products marketed to people are usually oral capsules, powders, or transdermal preparations. No human pharmacokinetic study exists, so there is no basis for any human dose or route, and none of the marketed forms has absorption data.", "source_ids": [ "mccoy-2013" ] }, { "q": "How much does dihexa cost?", "a": "It is not available through any licensed channel, so there is no pharmacy or telehealth price. Products sold as research chemicals are not lawful for human use and their identity and purity are not verified.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is dihexa banned by WADA?", "a": "Yes. Dihexa has no approval from any governmental health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times, in and out of competition.", "source_ids": [ "wada-list" ] }, { "q": "Dihexa vs semax: which has better evidence for cognition?", "a": "Semax has more human data. Semax is a registered prescription drug in Russia with decades of clinical use and Russian trial reports, and the FDA advisory committee recommended it for the 503A bulks list in July 2026. Dihexa has no human data of any kind, a retracted mechanism paper, and no identified lawful supply channel in the United States. Neither has an indexed randomized trial that meets Western regulatory standards.", "source_ids": [ "mccoy-2013", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "23055539", "title": "Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents", "year": 2013, "design": "Rat behavioral pharmacology (scopolamine induced amnesia and aged rat Morris water maze) plus hippocampal neuron culture; carries a 2021 expression of concern", "population": "Rats and cultured rat hippocampal neurons", "outcome": "Dihexa, an orally active blood brain barrier permeant analog, reversed scopolamine induced water maze deficits, improved aged rat performance, and increased synaptogenesis in culture", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/23055539/" }, { "pmid": "25187433", "title": "The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (retracted 2025)", "year": 2014, "design": "Mechanistic study in cultured neurons and rats; retracted by the journal in April 2025", "population": "Rats and cultured rat hippocampal neurons", "outcome": "Reported that dihexa binds HGF, potentiates c-Met phosphorylation, and that an HGF antagonist blocked its water maze effects; the article was retracted so these findings are not reliable", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/25187433/" } ], "sources": [ { "id": "mccoy-2013", "type": "pubmed", "title": "McCoy AT et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther 2013 (expression of concern 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/23055539/", "pmid": "23055539", "year": 2013 }, { "id": "benoist-2014-retracted", "type": "pubmed", "title": "Benoist CC et al. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther 2014 (retracted April 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/25187433/", "pmid": "25187433", "year": 2014 }, { "id": "wright-harding-2015", "type": "pubmed", "title": "Wright JW, Harding JW. The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer's disease. J Alzheimers Dis 2015 (review by the developers)", "url": "https://pubmed.ncbi.nlm.nih.gov/25649658/", "pmid": "25649658", "year": 2015 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "semax", "selank", "p21", "noopept" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Dihexa: evidence, side effects, and legal status", "description": "What dihexa is, what the rat memory studies show, the retracted mechanism paper, the cancer question, and why there is no lawful US source.", "h1": "Dihexa peptide", "headings": { "evidence": "Dihexa benefits: what the evidence shows", "safety": "Dihexa side effects" } } }, { "slug": "cerebrolysin", "name": "Cerebrolysin", "aliases": [ "Cerebrolysin concentrate", "Porcine brain derived peptide preparation", "FPF 1070", "Cerebrolysinum" ], "class": "Enzymatically digested porcine brain extract: a mixture of low molecular weight peptides (under 10 kDa) and free amino acids given by intravenous or intramuscular injection", "one_liner": "Porcine brain peptide mixture with several RCTs in stroke and dementia, mixed and low certainty results, approved in some countries but not by FDA.", "summary": "Cerebrolysin is a standardized mixture of small peptides and amino acids made from pig brain and sold as a neurotrophic drug in Austria, Russia, China, and dozens of other countries. Unlike most research peptides it has real randomized trials: a 1,070 patient acute stroke trial (CASTA) missed its primary endpoint, a 208 patient rehabilitation trial (CARS) found better arm function at 90 days, and Cochrane reviews rate the dementia evidence very low certainty and the stroke evidence as showing no mortality benefit with a possible increase in non-fatal serious adverse events. It has never been submitted to or approved by FDA and cannot be lawfully prescribed or compounded in the United States.", "mechanism": "Cerebrolysin is proposed to mimic the effects of endogenous neurotrophic factors such as BDNF, NGF, and CNTF, supporting neuronal survival, neurite outgrowth, and neurogenesis, and reducing excitotoxicity and free radical damage after ischemia. Because it is an undefined mixture, no single active peptide has been identified and the neurotrophic hypothesis rests on cell culture and rodent models of ischemia and neurodegeneration rather than a confirmed molecular target in humans.", "evidence_grade": "human_rct", "evidence_summary": "Multiple randomized placebo controlled trials exist, mostly industry supported and conducted in Europe and Asia. Acute ischemic stroke: CASTA (n = 1,070) found no difference on the combined primary endpoint at 90 days, with a post hoc trend in severe strokes. Post stroke rehabilitation: CARS (n = 208) found a large effect on Action Research Arm Test scores at day 90 (Mann-Whitney 0.71, 95% CI 0.63 to 0.79). The 2020 Cochrane review of 7 stroke trials (1,601 participants) found no difference in all-cause death (RR 0.90, 95% CI 0.61 to 1.32) and a possible increase in non-fatal serious adverse events (RR 2.15, 95% CI 1.01 to 4.55). Alzheimer's disease: a 2015 industry linked meta-analysis of 6 RCTs found a small cognitive benefit at 4 weeks (SMD minus 0.40) that was not significant at 6 months. Vascular dementia: the 2019 Cochrane review of 6 trials (597 participants) found small benefits rated very low certainty. Net: the grade is human RCT, but the effect is uncertain and likely small.", "human_evidence": "CASTA (2012): 1,070 patients with acute ischemic stroke randomized within 12 hours to 30 mL intravenous Cerebrolysin or saline daily for 10 days; the confirmatory combined endpoint (modified Rankin Scale, Barthel Index, NIHSS) at 90 days showed no significant difference, and a post hoc subgroup with NIHSS above 12 showed lower 90 day mortality (10.5% versus 20.2%). CARS (2016): 208 patients starting 24 to 72 hours after stroke, 30 mL daily for 21 days plus rehabilitation; Action Research Arm Test at day 90 favored Cerebrolysin with a Mann-Whitney estimator of 0.71. Alvarez et al. (2006): 279 patients with mild to moderate Alzheimer's disease randomized to 10, 30, or 60 mL or placebo for 12 weeks; only the 10 mL dose improved ADAS-cog at 24 weeks. Cochrane 2020 (7 trials, 1,601 participants) and Cochrane 2019 (6 trials, 597 participants) both judged the evidence to be low or very low certainty with high risk of bias and industry funding in most trials.", "animal_evidence": "Rodent models of focal ischemia, traumatic brain injury, and transgenic Alzheimer's disease report reduced infarct volume, less amyloid pathology, and improved behavioral recovery with Cerebrolysin, and cell culture work shows neurotrophic like effects on neuronal survival and neurite growth. These models informed the neurotrophic hypothesis but do not identify which peptides in the mixture are responsible.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Trial regimens, all by intravenous infusion: 30 mL daily for 10 days starting within 12 hours of stroke (CASTA); 30 mL daily for 21 days starting 24 to 72 hours after stroke alongside rehabilitation (CARS); 10, 30, or 60 mL five days a week for 4 weeks then twice weekly for 8 weeks in Alzheimer's disease (Alvarez 2006). These are the regimens used in cited studies, not a recommendation, and none is approved in the United States.", "routes": [ "Intravenous infusion (all major trials)", "Intramuscular injection (approved labeling in some countries for smaller volumes)" ], "side_effects": [ "Possible increase in non-fatal serious adverse events in acute stroke (RR 2.15, 95% CI 1.01 to 4.55 in the 2020 Cochrane review, more pronounced with the 30 mL for 10 days regimen)", "No difference in all-cause death or total adverse events versus placebo in stroke trials", "Adverse event rates similar to placebo in Alzheimer's disease trials (dizziness, headache, agitation, and feeling hot reported)", "Injection site reactions and rare allergic reactions per non-US labeling", "Rapid infusion can cause feeling hot, sweating, or dizziness per non-US labeling", "Theoretical prion transmission concern from porcine brain source, not documented in humans" ], "interactions": [ "No formal human interaction studies published in the indexed literature", "Non-US labeling advises caution with antidepressants and MAO inhibitors because of possible additive effects (basis not established in trials)", "Non-US labeling advises against mixing in the same infusion with balanced amino acid solutions" ], "contraindications": [ "Epilepsy or seizure disorder per non-US labeling", "Severe renal impairment per non-US labeling", "Known hypersensitivity to any component", "Pregnancy and breastfeeding (no controlled data)" ], "wada_status": "not_prohibited", "fda_status": "unscheduled", "compounding_status": "Cerebrolysin has never been submitted to or reviewed by FDA and is not an FDA approved drug. As an undefined biological mixture derived from animal brain it is not a bulk drug substance eligible for 503A or 503B compounding, and it has not been nominated to the 503A bulks list. It is a registered prescription drug in Austria (where it is manufactured), Russia, China, South Korea, and many other countries. Importing it for personal use in the United States is not lawful under FDA rules except in narrow circumstances that do not apply to routine use.", "typical_cost": "Not available through licensed channels in the United States. In countries where it is approved, pharmacy prices are roughly 30 to 80 USD per 10 mL ampoule, so a 10 to 20 day course of 30 mL daily costs roughly 900 to 4,800 USD in drug alone. Prices noted on the last verified date and vary by country.", "access_path": [ "Not legally available in the United States: no FDA approved product and no compounding pathway.", "Prescription in countries where it is registered (Austria, Russia, China, and others), administered by infusion in a clinic.", "Products imported or sold online for US use are not lawful and are not verified for cold chain or authenticity." ], "faqs": [ { "q": "Is Cerebrolysin legal in the United States?", "a": "No, not for prescription or sale. Cerebrolysin has never been submitted to or approved by FDA, it cannot be compounded because it is an undefined animal derived mixture rather than a bulk drug substance, and importing unapproved drugs for personal use is generally not permitted. It is a legitimately registered prescription drug in Austria, Russia, China, and many other countries, where it is given by infusion in clinical settings.", "source_ids": [ "fda-503a-bulks", "cochrane-stroke-2020" ] }, { "q": "Does Cerebrolysin work for stroke?", "a": "The evidence is mixed. The largest trial, CASTA, randomized 1,070 acute stroke patients to 30 mL daily for 10 days or placebo and found no significant difference on its primary combined outcome at 90 days, with a post hoc trend toward benefit in severe strokes. The smaller CARS trial (n = 208) started treatment 1 to 3 days after stroke alongside rehabilitation and found better arm function at 90 days. The 2020 Cochrane review of 7 trials (1,601 participants) concluded that Cerebrolysin probably has little or no effect on death and may increase non-fatal serious adverse events.", "source_ids": [ "casta", "cars", "cochrane-stroke-2020" ] }, { "q": "Does Cerebrolysin work for dementia or Alzheimer's disease?", "a": "Modestly at best, with low certainty. A 2015 meta-analysis of 6 randomized trials in mild to moderate Alzheimer's disease, co-authored by the manufacturer's staff, found a small cognitive benefit at 4 weeks (standardized mean difference minus 0.40) that was no longer significant at 6 months. The 2019 Cochrane review of 6 trials in vascular dementia (597 participants) found small improvements in cognition and global function but rated the evidence very low certainty because of bias, heterogeneity, and industry funding, and warned any benefit may be too small to matter clinically.", "source_ids": [ "gauthier-2015", "cochrane-vad-2019", "alvarez-2006" ] }, { "q": "What are the side effects of Cerebrolysin?", "a": "In trials, total adverse events and deaths were similar to placebo. The main safety signal is from the 2020 Cochrane stroke review, which found a possible increase in non-fatal serious adverse events (risk ratio 2.15, 95% CI 1.01 to 4.55), more pronounced with the 30 mL for 10 days regimen. Non-US labeling lists dizziness, headache, agitation, feeling hot with rapid infusion, and rare allergic reactions, and contraindicates it in epilepsy and severe kidney disease. Because it comes from pig brain there is a theoretical but undocumented prion concern.", "source_ids": [ "cochrane-stroke-2020", "alvarez-2006" ] }, { "q": "How is Cerebrolysin given?", "a": "In the trials it was given by intravenous infusion in a clinic, in daily courses of about 10 to 21 days after stroke and in longer courses in Alzheimer's disease. Non-US labeling also allows intramuscular use. It is not a self injected product, and no regimen is approved in the United States.", "source_ids": [ "casta", "cars", "alvarez-2006" ] }, { "q": "How much does Cerebrolysin cost?", "a": "There is no US price because it is not lawfully available here. In countries where it is registered, pharmacy prices run roughly 30 to 80 USD per 10 mL ampoule, so a course of 30 mL daily for 10 to 20 days costs roughly 900 to 4,800 USD in drug alone, before clinic and infusion fees. Prices were noted on the last verified date and vary widely by country.", "source_ids": [ "cochrane-stroke-2020" ] }, { "q": "Is Cerebrolysin banned by WADA?", "a": "No. Section S0 of the WADA Prohibited List covers substances with no approval from any governmental health authority, and Cerebrolysin is an approved prescription drug in Austria and many other countries. It is not listed in any other section of the 2026 list or the 2027 list published in September 2026. Athletes should still confirm with their anti-doping organization, since list interpretations can change.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "Cerebrolysin vs semax: which has better evidence?", "a": "Cerebrolysin, by a wide margin, though neither is FDA approved. Cerebrolysin has several indexed randomized placebo controlled trials, including a 1,070 patient stroke trial and Cochrane reviews, even if the results are mixed and low certainty. Semax has Russian clinical reports and no indexed randomized trial. On US access the picture reverses: the FDA advisory committee recommended semax for the 503A bulks list in July 2026, while Cerebrolysin has no US pathway at all.", "source_ids": [ "cochrane-stroke-2020", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "22282884", "title": "Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial (CASTA)", "year": 2012, "design": "Randomized, double blind, placebo controlled trial, treatment within 12 hours of onset, 90 day follow up", "n": 1070, "population": "Adults with acute ischemic hemispheric stroke in Asia, on aspirin", "outcome": "No significant difference on the combined primary endpoint (modified Rankin Scale, Barthel Index, NIHSS) at 90 days; post hoc trend to benefit and lower mortality (10.5% versus 20.2%) in patients with NIHSS above 12", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22282884/" }, { "pmid": "26564102", "title": "Cerebrolysin and Recovery After Stroke (CARS): a randomized, placebo-controlled, double-blind, multicenter trial", "year": 2016, "design": "Randomized, double blind, placebo controlled multicenter trial, 21 days of treatment plus rehabilitation, 90 day follow up", "n": 208, "population": "Adults 24 to 72 hours after ischemic stroke entering early rehabilitation", "outcome": "Action Research Arm Test at day 90 favored Cerebrolysin (Mann-Whitney estimator 0.71, 95% CI 0.63 to 0.79); authors called the study exploratory and asked for confirmation", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26564102/" }, { "pmid": "32662068", "title": "Cerebrolysin for acute ischaemic stroke (Cochrane review, 2020 update)", "year": 2020, "design": "Cochrane systematic review and meta-analysis of 7 randomized trials", "n": 1601, "population": "Adults with acute ischemic stroke treated within 48 hours of onset", "outcome": "No difference in all-cause death (RR 0.90, 95% CI 0.61 to 1.32, moderate certainty); possible increase in non-fatal serious adverse events (RR 2.15, 95% CI 1.01 to 4.55); most trials industry supported", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/32662068/" }, { "pmid": "16420392", "title": "A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease", "year": 2006, "design": "Randomized, double blind, placebo controlled dose ranging trial, 12 weeks of infusions, 24 week follow up", "n": 279, "population": "Adults with mild to moderate Alzheimer's disease", "outcome": "Only the 10 mL dose improved ADAS-cog at week 24 (p = 0.038); 30 and 60 mL improved global impression but not cognition; adverse events similar across groups", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16420392/" }, { "pmid": "25832905", "title": "Cerebrolysin in mild-to-moderate Alzheimer's disease: a meta-analysis of randomized controlled clinical trials", "year": 2015, "design": "Meta-analysis of 6 randomized double blind placebo controlled trials of 30 mL per day; manufacturer employees among the authors", "population": "Adults with mild to moderate Alzheimer's disease", "outcome": "Cognitive benefit at 4 weeks (SMD minus 0.40, 95% CI minus 0.66 to minus 0.13) not sustained at 6 months (SMD minus 0.37, 95% CI minus 0.90 to 0.16); global clinical change favored Cerebrolysin at both timepoints", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25832905/" }, { "pmid": "31710397", "title": "Cerebrolysin for vascular dementia (Cochrane review, 2019 update)", "year": 2019, "design": "Cochrane systematic review and meta-analysis of 6 randomized trials", "n": 597, "population": "Adults with mild to moderate vascular dementia, mostly in China and Russia", "outcome": "Small benefit on cognition (SMD 0.36, 95% CI 0.13 to 0.58) and global function (RR 2.69 for response) rated very low certainty; high risk of bias and industry funding; no new trials since 2013", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31710397/" } ], "sources": [ { "id": "casta", "type": "pubmed", "title": "Heiss WD et al. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke 2012 (CASTA)", "url": "https://pubmed.ncbi.nlm.nih.gov/22282884/", "pmid": "22282884", "year": 2012 }, { "id": "cars", "type": "pubmed", "title": "Muresanu DF et al. Cerebrolysin and Recovery After Stroke (CARS): a randomized, placebo-controlled, double-blind, multicenter trial. Stroke 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26564102/", "pmid": "26564102", "year": 2016 }, { "id": "cochrane-stroke-2020", "type": "pubmed", "title": "Ziganshina LE, Abakumova T, Hoyle CH. Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32662068/", "pmid": "32662068", "year": 2020 }, { "id": "alvarez-2006", "type": "pubmed", "title": "Alvarez XA et al. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. Eur J Neurol 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16420392/", "pmid": "16420392", "year": 2006 }, { "id": "gauthier-2015", "type": "pubmed", "title": "Gauthier S et al. Cerebrolysin in mild-to-moderate Alzheimer's disease: a meta-analysis of randomized controlled clinical trials. Dement Geriatr Cogn Disord 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25832905/", "pmid": "25832905", "year": 2015 }, { "id": "cochrane-vad-2019", "type": "pubmed", "title": "Cui S et al. Cerebrolysin for vascular dementia. Cochrane Database Syst Rev 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31710397/", "pmid": "31710397", "year": 2019 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 } ], "related": [ "semax", "selank", "noopept", "dihexa" ], "cluster": "cognitive", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Cerebrolysin: evidence, side effects, and legal status", "headings": { "evidence": "Cerebrolysin benefits: what the evidence shows", "safety": "Cerebrolysin side effects" } } }, { "slug": "p21", "name": "P21", "aliases": [ "P021", "Ac-DGGLAG-NH2", "CNTF peptide mimetic", "Peptide 021", "P21 peptide", "P021 peptide" ], "class": "Synthetic adamantane-modified tetrapeptide derived from the active region of ciliary neurotrophic factor (CNTF)", "one_liner": "Lab-made peptide mimicking part of CNTF, a protein that keeps nerve cells alive; mouse and rat memory and Alzheimer data; no human studies of any kind.", "summary": "P21 (P021) is a small synthetic peptide designed at the New York State Institute for Basic Research to mimic a fragment of ciliary neurotrophic factor (CNTF), a protein that supports nerve cell survival. In mice it improves learning and memory, increases hippocampal neurogenesis (new nerve cells in the brain's memory center), and in a triple transgenic Alzheimer model (mice bred to develop Alzheimer-like disease) reduces tau hyperphosphorylation, the protein change behind Alzheimer tangles, but no human trial or safety study has ever been published, so its evidence grade is animal-only. It has never been reviewed by FDA, is not on any 503A compounding list (FDA's lists of ingredients pharmacies may use), and is prohibited in sport under WADA section S0, the anti-doping ban on unapproved substances.", "mechanism": "P21 is proposed to act as a CNTF mimetic that inhibits leukemia inhibitory factor (LIF) signaling and increases brain-derived neurotrophic factor (BDNF) expression, which in turn promotes neurogenesis, neuronal maturation, and synaptic plasticity in the dentate gyrus. In the 3xTg-AD mouse it also reduced abnormal tau phosphorylation and soluble amyloid beta, an effect the authors attributed to increased BDNF activity. The adamantane modification was added to improve blood brain barrier penetration and oral stability. All of this comes from rodent and cell work.", "evidence_grade": "animal_only", "evidence_summary": "Evidence consists of rodent studies from a single research group. Peripheral P21 improved short-term and spatial memory and increased dentate gyrus neurogenesis in normal adult mice (2010). Twelve months of oral P021 in 3xTg-AD mice starting at 9 to 10 months of age reduced tau pathology, lowered soluble amyloid beta, and rescued cognition, neurogenesis, and synaptic plasticity (2014). Later work reported effects in aged rats and mouse models of retinal degeneration and early development. No independent replication and no human data have been published.", "human_evidence": "No human study of P21 has been published. No clinical trial registration, pharmacokinetic study, or safety report in humans was identified as of the last verification date.", "animal_evidence": "In normal C57BL/6 mice, peripheral P21 enhanced learning, short-term memory, and spatial reference memory and increased neurogenesis and maturation of newborn neurons in the dentate gyrus. In female 3xTg-AD mice fed P021 in the diet for 12 months, tau hyperphosphorylation at Alzheimer associated sites and soluble amyloid beta were reduced, and deficits in cognition, neurogenesis, and synaptic plasticity were rescued. Chronic treatment was described as well tolerated in mice, but formal toxicology has not been published.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Not established in human literature. Mouse studies delivered P021 orally in the diet or by peripheral injection at research doses that have no established human equivalent.", "routes": [ "Oral in diet (mouse studies)", "Peripheral injection (mouse studies)", "Sold as oral capsules or injection by research chemical sellers (not lawful for human use)" ], "side_effects": [ "No human safety data of any kind", "Rodent studies did not report toxicity, but no formal toxicology has been published", "Theoretical concern that a growth factor mimetic could influence tumor growth (not studied)" ], "interactions": [ "No interaction data exist in any species" ], "contraindications": [ "No human use is supported by evidence", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "P21 has never been nominated to or reviewed for the FDA 503A or 503B bulks lists and does not appear in any category on the FDA Category 2 page (current as of April 22, 2026). It is not a component of any approved drug, so a 503A pharmacy has no lawful basis to compound it. It is not an FDA approved drug.", "typical_cost": "Not available through licensed channels. Research chemical sellers list it, but those products are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available for human use in the United States.", "Not an FDA approved drug and not compoundable under 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is P21 legal in the United States?", "a": "P21 is not an approved drug anywhere, has never been reviewed by FDA for compounding (custom-making by a pharmacy), and is not a component of any approved product, so there is no lawful route to obtain it for human use. It is sold online as a research chemical, and those products are not intended or permitted for people. Possession is not a criminal matter, but no clinic or pharmacy can lawfully dispense it.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Does P21 work for memory or Alzheimer's disease?", "a": "In mice, yes: P21 improved learning and memory in normal adult mice and, given orally for 12 months, reduced tau pathology and rescued cognition in a triple transgenic Alzheimer model. In humans, nobody knows. There has never been a human trial, a pharmacokinetic study, or a published safety report. PeptideAgent grades the evidence animal-only.", "source_ids": [ "li-2010", "kazim-2014" ] }, { "q": "What are the side effects of P21?", "a": "There are no human safety data at all. Mouse studies did not report toxicity during chronic dosing, but no formal toxicology has been published. Because P21 mimics a neurotrophic growth factor, a theoretical effect on tumor growth has not been ruled out.", "source_ids": [ "kazim-2014", "kazim-2016" ] }, { "q": "How is P21 taken?", "a": "In research it was given to mice in the diet or by peripheral injection. It is sold to people as capsules or injection vials with doses that are extrapolated from rodent work rather than measured in humans. No human dose has ever been established.", "source_ids": [ "li-2010", "kazim-2014" ] }, { "q": "How much does P21 cost?", "a": "It is not available through licensed channels, so there is no pharmacy or telehealth price. Research chemical listings exist but are not lawful for human use and are not tested for purity, so PeptideAgent does not report those prices as a cost of treatment.", "source_ids": [ "fda-cat2" ] }, { "q": "Is P21 banned by WADA?", "a": "Yes. P21 has no approval from any government health authority for human use, which places it in section S0 (non-approved substances) of the WADA Prohibited List. It is prohibited at all times, in and out of competition.", "source_ids": [ "wada-list" ] }, { "q": "P21 vs Dihexa: which has better evidence?", "a": "Neither has any human data. Both are small synthetic cognitive peptides developed in academic labs, both improved memory in rodents, and both are sold only as research chemicals. P21 has a longer chronic dosing study in an Alzheimer mouse model (12 months); Dihexa was placed on and then withdrawn from the FDA Category 2 compounding list, while P21 has never been nominated at all. Both are animal-only.", "source_ids": [ "kazim-2014", "fda-cat2" ] } ], "studies": [ { "pmid": "20600002", "title": "Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice", "year": 2010, "design": "Mouse behavioral and histological study of peripherally administered P21", "population": "Normal adult C57BL/6 mice", "outcome": "P21 enhanced learning, short-term and spatial reference memory, and increased neurogenesis and maturation of newborn neurons in the dentate gyrus", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/20600002/" }, { "pmid": "25046994", "title": "Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease", "year": 2014, "design": "12 month oral (dietary) treatment study in a transgenic mouse model", "population": "Female 3xTg-AD and wild type mice treated from 9 to 10 months of age", "outcome": "Reduced tau hyperphosphorylation and soluble amyloid beta, increased BDNF activity, and rescued cognition, neurogenesis, and synaptic plasticity", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/25046994/" }, { "pmid": "27400746", "title": "Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease", "year": 2016, "design": "Narrative review", "population": "Rodent models of Alzheimer's disease and aging", "outcome": "Summarizes the CNTF mimetic rationale for P021 and the rodent evidence; notes that human studies have not been performed", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/27400746/" } ], "sources": [ { "id": "li-2010", "type": "pubmed", "title": "Li B et al. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett 2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20600002/", "pmid": "20600002", "year": 2010 }, { "id": "kazim-2014", "type": "pubmed", "title": "Kazim SF et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Neurobiol Dis 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25046994/", "pmid": "25046994", "year": 2014 }, { "id": "kazim-2016", "type": "pubmed", "title": "Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27400746/", "pmid": "27400746", "year": 2016 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "dihexa", "semax", "noopept", "cerebrolysin" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "P21 (P021) peptide: evidence and legal status", "h1": "P21 peptide (P021)" } }, { "slug": "noopept", "name": "Noopept", "aliases": [ "GVS-111", "N-phenylacetyl-L-prolylglycine ethyl ester", "Omberacetam", "Noopept tablets" ], "class": "Synthetic dipeptide-like nootropic (proline-glycine ethyl ester with a phenylacetyl group), structurally related to piracetam", "one_liner": "A dipeptide-like memory drug approved in Russia, with small open-label human studies, no placebo-controlled RCT indexed in English, and no FDA review.", "summary": "Noopept (GVS-111, omberacetam) is a synthetic compound resembling a dipeptide (two linked amino acids) developed at the Zakusov Institute of Pharmacology in Moscow and sold as a prescription nootropic (memory and focus drug) in Russia. The human evidence consists of small open-label Russian studies (everyone knew what they were taking) in people with mild cognitive impairment (memory and thinking problems short of dementia) after stroke, brain injury, or vascular disease, which report modest improvements at 20 mg per day, so PeptideAgent grades it human observational. It has never been approved or reviewed by FDA and is sold in the United States as an unapproved supplement ingredient.", "mechanism": "Noopept is metabolized to cycloprolylglycine, an endogenous dipeptide. In rodent and cell studies it increases expression of brain-derived neurotrophic factor and nerve growth factor in the hippocampus, enhances inhibitory synaptic transmission through alpha-7 nicotinic receptors on interneurons, and reduces apoptosis and tau hyperphosphorylation in an Alzheimer cell model. It is also described as anxiolytic in animals. Which of these mechanisms matters in people has not been established.", "evidence_grade": "human_observational", "evidence_summary": "Human data are limited to small Russian studies. An open comparative study of Noopept 20 mg per day versus piracetam in patients with mild cognitive disorders of vascular or traumatic origin reported greater improvement with Noopept. An open prospective study of 60 stroke patients reported improved MMSE and associative test scores after 2 months at 20 mg per day compared with untreated controls. None of these were double-blind placebo-controlled trials, and no trial outside Russia has been indexed.", "human_evidence": "Neznamov and Teleshova (2009) compared Noopept (20 mg per day) with piracetam in an open comparative study of patients with mild cognitive disorders due to organic brain disease of vascular and traumatic origin and reported a broader and faster effect with Noopept, particularly on attention, memory, and anxiety. Amelin et al. (2011) treated 60 stroke patients with Noopept 20 mg per day in an open prospective study and reported significant improvement in MMSE and associative tests after 2 months versus controls, with good tolerability. Neither study was placebo-controlled or double-blind.", "animal_evidence": "In rats and rat hippocampal slices, Noopept enhanced inhibitory synaptic transmission through alpha-7 nicotinic receptors on interneurons. In an Alzheimer related cellular model it reduced apoptosis and tau hyperphosphorylation. Rat studies also report normalization of incretin system parameters in experimental diabetes. Rodent behavioral studies from the developing laboratory report memory enhancement and anxiolytic effects.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Human studies used 10 mg orally twice daily (20 mg per day) for 2 months (Amelin 2011) or for the duration of the comparative study (Neznamov 2009). No dose finding study has been published in English.", "routes": [ "Oral tablet (Russian prescription product, 10 mg)", "Oral capsule or powder (sold in the United States as an unapproved supplement ingredient)", "Sublingual and intranasal use reported anecdotally (no studies)" ], "side_effects": [ "Open-label Russian studies describe good tolerability; no systematic placebo-controlled safety data", "Irritability, sleep disturbance, and headache reported anecdotally", "Blood pressure increase reported in some patients in the Russian literature", "No long-term safety data outside Russia" ], "interactions": [ "No formal interaction studies exist", "Theoretical additive effects with other nootropics, stimulants, or drugs acting on nicotinic receptors" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "Severe hepatic or renal impairment (no data; listed as a precaution in Russian labeling)", "Children (no data)" ], "wada_status": "unclear", "fda_status": "unscheduled", "compounding_status": "Noopept has never been nominated to or reviewed for the FDA 503A or 503B bulks lists and does not appear on the FDA Category 2 page (current as of April 22, 2026). It is not a component of any FDA approved drug. In the United States it is sold as a dietary supplement ingredient, but it is a synthetic drug substance approved in Russia and does not meet the definition of a dietary ingredient, so its sale as a supplement is not an approved use. It is not compoundable under 503A or 503B.", "typical_cost": "Sold as an unapproved supplement in the United States at roughly 15 to 40 USD per month; not available through licensed pharmacy or telehealth channels.", "access_path": [ "Prescription product in Russia and some other former Soviet countries.", "Not an FDA approved drug and not compoundable in the United States.", "Sold online as an unapproved supplement ingredient; identity and purity are not verified." ], "faqs": [ { "q": "Is Noopept legal in the United States?", "a": "Noopept is not an FDA approved drug and has never been reviewed for compounding. It is widely sold online as a supplement ingredient, but because it is a synthetic drug substance approved as a prescription medicine in Russia, it does not meet the legal definition of a dietary ingredient (the substances allowed in supplements) and its sale as a supplement is not an approved use. Possession is not a criminal matter. No US pharmacy can lawfully compound (custom-make) it.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Does Noopept actually work for memory?", "a": "The human evidence is weak. Small open-label Russian studies in people with mild cognitive impairment after stroke or brain injury reported modest improvements on tests like the MMSE after 2 months at 20 mg per day, and one comparative study found it outperformed piracetam. None of these were placebo-controlled or double-blind, and no trial in healthy people has been published. PeptideAgent grades the evidence human observational.", "source_ids": [ "neznamov-2009", "amelin-2011" ] }, { "q": "What are the side effects of Noopept?", "a": "The Russian studies describe good tolerability at 20 mg per day, but they were small and open-label. Anecdotal reports mention irritability, sleep disturbance, headache, and blood pressure increases. There are no long-term or placebo-controlled safety data, and no safety data at the higher doses sometimes used off-label.", "source_ids": [ "amelin-2011", "neznamov-2009" ] }, { "q": "How is Noopept taken?", "a": "By mouth, as tablets. The published human studies used oral dosing for about 2 months. Sublingual and intranasal use are described online but have not been studied. Noopept is not an approved drug in the United States, so there is no US labeled dose. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "amelin-2011", "neznamov-2009" ] }, { "q": "How much does Noopept cost?", "a": "As an unapproved supplement it is inexpensive, roughly 15 to 40 USD per month, but those products are not verified for identity or purity and are not sold through licensed channels. There is no pharmacy or telehealth price in the United States.", "source_ids": [ "fda-cat2" ] }, { "q": "Is Noopept banned by WADA?", "a": "It is not named on the WADA Prohibited List. Section S0 covers substances with no approval from any government health authority, and Noopept is approved as a prescription drug in Russia, so S0 does not clearly apply. PeptideAgent lists its status as unclear; athletes should ask their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "Noopept vs Semax: which is better?", "a": "Both are Russian nootropics with small, mostly open-label human studies and no placebo-controlled trial indexed in English. Noopept is an oral dipeptide-like compound studied at 20 mg per day for mild cognitive impairment. Semax is a nasal heptapeptide. Neither is FDA approved; Semax was placed on and then withdrawn from the FDA Category 2 compounding list, while Noopept has never been nominated. There is no head to head trial.", "source_ids": [ "neznamov-2009", "fda-cat2" ] }, { "q": "How does Noopept work?", "a": "It is converted in the body to cycloprolylglycine, a naturally occurring dipeptide. In rat brain tissue it increases BDNF and NGF expression, enhances inhibitory transmission through alpha-7 nicotinic receptors, and in an Alzheimer cell model it reduced tau hyperphosphorylation and apoptosis. Whether these mechanisms operate at human doses has not been shown.", "source_ids": [ "ostrovskaya-2014", "kondratenko-2022" ] } ], "studies": [ { "pmid": "19234797", "title": "Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin", "year": 2009, "design": "Open comparative clinical study, Noopept 20 mg per day versus piracetam", "population": "Adults with mild cognitive disorders due to organic brain disease of vascular or traumatic origin", "outcome": "Noopept produced broader and faster improvement than piracetam on cognitive and anxiety measures; no placebo arm", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/19234797/" }, { "pmid": "22500312", "title": "Noopept in the treatment of mild cognitive impairment in patients with stroke", "year": 2011, "design": "Open prospective study with untreated control group, 20 mg per day for 2 months within a 12 month follow up", "n": 60, "population": "Adults with mild cognitive impairment after stroke", "outcome": "Significant improvement in MMSE and lateral and categorical association tests after 2 months versus controls; good tolerability", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/22500312/" }, { "pmid": "25096780", "title": "Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation", "year": 2014, "design": "In vitro cellular model of Alzheimer related toxicity", "population": "Cultured neuronal cells exposed to amyloid beta", "outcome": "Noopept reduced apoptosis and tau hyperphosphorylation", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/25096780/" }, { "pmid": "36195298", "title": "Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves alpha-7 AChRs on interneurons in hippocampal slices from rat", "year": 2022, "design": "Rat hippocampal slice electrophysiology", "population": "Rat hippocampal slices", "outcome": "Noopept enhanced inhibitory input to CA1 pyramidal neurons via alpha-7 nicotinic receptors on interneurons", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/36195298/" } ], "sources": [ { "id": "neznamov-2009", "type": "pubmed", "title": "Neznamov GG, Teleshova ES. Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin. Neurosci Behav Physiol 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19234797/", "pmid": "19234797", "year": 2009 }, { "id": "amelin-2011", "type": "pubmed", "title": "Amelin AV et al. Noopept in the treatment of mild cognitive impairment in patients with stroke. Zh Nevrol Psikhiatr Im S S Korsakova 2011 (Russian)", "url": "https://pubmed.ncbi.nlm.nih.gov/22500312/", "pmid": "22500312", "year": 2011 }, { "id": "ostrovskaya-2014", "type": "pubmed", "title": "Ostrovskaya RU et al. Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation. J Biomed Sci 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25096780/", "pmid": "25096780", "year": 2014 }, { "id": "kondratenko-2022", "type": "pubmed", "title": "Kondratenko RV et al. Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves alpha-7 AChRs on interneurons in hippocampal slices from rat. Neurosci Lett 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36195298/", "pmid": "36195298", "year": 2022 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "semax", "selank", "p21", "cerebrolysin" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Noopept: evidence, side effects, and legal status" } }, { "slug": "pinealon", "name": "Pinealon", "aliases": [ "EDR peptide", "Glu-Asp-Arg", "L-glutamyl-L-aspartyl-L-arginine", "Khavinson peptide", "Pinealon peptide" ], "class": "Synthetic tripeptide (Glu-Asp-Arg) from the Khavinson family of short peptide bioregulators", "one_liner": "Three amino acid peptide from Russia's Khavinson bioregulator family, sold there as a brain supplement; rat and cell data only, no controlled human trial.", "summary": "Pinealon is a synthetic tripeptide, a chain of three amino acids (Glu-Asp-Arg), developed at the St. Petersburg Institute of Bioregulation and Gerontology and sold in Russia as a dietary supplement for brain function. Its evidence consists of rat and cell culture studies (cells grown in a dish) from the developing group, including protection of rat offspring from prenatal hyperhomocysteinemia (high levels of the amino acid homocysteine before birth); no randomized human trial has been indexed, so PeptideAgent grades it animal-only. It has never been reviewed by FDA, is not an approved drug anywhere, and is prohibited in sport under WADA section S0, the anti-doping ban on unapproved substances.", "mechanism": "The developers propose that short peptides such as Pinealon enter cells and the nucleus and bind DNA to modulate gene expression, including genes involved in neuronal differentiation, antioxidant defense, and the pathogenesis of Alzheimer's disease. In rat neurons it reduced reactive oxygen species accumulation and necrosis under oxidative stress. These proposals rest on in vitro, molecular modeling, and rodent work from a single research group and have not been independently confirmed or tested in humans.", "evidence_grade": "animal_only", "evidence_summary": "Published evidence comes from the Khavinson group in St. Petersburg. In rats with methionine induced hyperhomocysteinemia during pregnancy, Pinealon improved spatial orientation and learning in the offspring and reduced reactive oxygen species and necrotic cells in isolated cerebellar neurons. A 2020 review describes proposed effects on gene expression relevant to Alzheimer's disease based on cell and computational work. A Russian language review reports use of short peptides in older people, but no randomized controlled trial has been indexed and no independent laboratory has replicated the findings.", "human_evidence": "No indexed randomized controlled trial identified. A 2013 Russian language review from the developing group describes neuroprotective use of peptide bioregulators including short peptides in people of various ages, but design details are not available in an indexed abstract and it is not a controlled trial. No pharmacokinetic or safety study in humans has been published.", "animal_evidence": "In pregnant rats loaded with dietary methionine to induce hyperhomocysteinemia, Pinealon administration improved the offspring's spatial orientation and learning ability and decreased reactive oxygen species accumulation and the number of necrotic cells among isolated cerebellar neurons. In vitro work from the same group reports antioxidant and neuroprotective effects in neuronal cultures.", "conditions": [ "cognitive-decline" ], "literature_dosing": "Not established in human literature. Rat studies used research doses with no established human equivalent. Russian supplement labeling for Pinealon capsules is not based on any published dose finding study.", "routes": [ "Oral capsule (sold as a supplement in Russia)", "Subcutaneous or intranasal use described by sellers (no studies)", "Injection (rat studies)" ], "side_effects": [ "No human safety data of any kind", "Rodent studies did not report toxicity, but no formal toxicology has been published", "Injection site reactions are plausible for injected products (not studied)" ], "interactions": [ "No interaction data exist in any species" ], "contraindications": [ "No human use is supported by evidence", "Pregnancy and breastfeeding (no human data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Pinealon has never been nominated to or reviewed for the FDA 503A or 503B bulks lists and does not appear on the FDA Category 2 page (current as of April 22, 2026). It is not a component of any approved drug, so a 503A pharmacy has no lawful basis to compound it. It is not an FDA approved drug and is sold in Russia only as a supplement, not a medicine.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available for human use in the United States.", "Not an FDA approved drug and not compoundable under 503A or 503B.", "Sold as a supplement in Russia; imported and research use only products are not verified for identity or purity." ], "faqs": [ { "q": "What is pinealon?", "a": "Pinealon is a synthetic three amino acid peptide (Glu-Asp-Arg) from the St. Petersburg Institute of Bioregulation and Gerontology, sold in Russia as a dietary supplement for brain function. Its evidence is rat and cell culture work (cells grown in a dish) from the developing group, and it is not an approved drug anywhere.", "source_ids": [ "arutjunyan-2012", "khavinson-2020" ] }, { "q": "Is Pinealon legal in the United States?", "a": "Pinealon is not an approved drug anywhere and has never been reviewed by FDA for compounding, so there is no lawful route to obtain it for human use in the United States. It is sold as a supplement in Russia and imported or sold online as a research chemical. Possession is not a criminal matter, but no US clinic or pharmacy can lawfully dispense it.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Does Pinealon work for memory or brain aging?", "a": "There is no controlled human evidence. The published studies are from the developing laboratory in rats and cell cultures, where it improved learning in rat offspring exposed to prenatal hyperhomocysteinemia and protected neurons from oxidative stress. A Russian language review describes use in older people but is not a randomized trial. PeptideAgent grades the evidence animal-only.", "source_ids": [ "arutjunyan-2012", "umnov-2013" ] }, { "q": "What are the side effects of Pinealon?", "a": "No human safety data have been published. Rodent studies did not report toxicity, but formal toxicology is not available. Injected products carry the usual risks of unverified research chemicals, including contamination and incorrect identity.", "source_ids": [ "arutjunyan-2012", "fda-cat2" ] }, { "q": "How is Pinealon taken?", "a": "In Russia it is sold as oral capsules. Sellers elsewhere describe subcutaneous and intranasal use. None of these routes or doses has been studied in humans; the only published dosing is in rats.", "source_ids": [ "arutjunyan-2012" ] }, { "q": "How much does Pinealon cost?", "a": "It is not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-cat2" ] }, { "q": "Is Pinealon banned by WADA?", "a": "Yes. Pinealon has no approval from any government health authority as a medicine for human use, which places it in section S0 (non-approved substances) of the WADA Prohibited List. It is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "Pinealon vs Epitalon: what is the difference?", "a": "Both are short Khavinson peptides from the same St. Petersburg group. Epitalon is a tetrapeptide (Ala-Glu-Asp-Gly) marketed for longevity and telomere effects; Pinealon is a tripeptide (Glu-Asp-Arg) marketed for brain function. Epitalon was placed on the FDA Category 2 compounding list, withdrawn in April 2026, and recommended for the 503A bulks list by the advisory committee in July 2026; Pinealon has never been nominated. Neither has a randomized human trial indexed in English.", "source_ids": [ "khavinson-2020", "fda-cat2", "fda-pcac" ] } ], "studies": [ { "pmid": "22567179", "title": "Pinealon protects the rat offspring from prenatal hyperhomocysteinemia", "year": 2012, "design": "Rat study of maternal Pinealon treatment during methionine induced hyperhomocysteinemia in pregnancy", "population": "Pregnant rats and their offspring", "outcome": "Offspring of treated dams showed improved spatial orientation and learning and fewer necrotic cerebellar neurons with less reactive oxygen species accumulation", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/22567179/" }, { "pmid": "33396470", "title": "EDR peptide: possible mechanism of gene expression and protein synthesis regulation involved in the pathogenesis of Alzheimer's disease", "year": 2020, "design": "Review with molecular modeling and cell culture data", "population": "Cell cultures and computational models", "outcome": "Proposes that Glu-Asp-Arg binds DNA and modulates expression of genes relevant to Alzheimer pathology; no human data", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/33396470/" } ], "sources": [ { "id": "arutjunyan-2012", "type": "pubmed", "title": "Arutjunyan A et al. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Int J Clin Exp Med 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22567179/", "pmid": "22567179", "year": 2012 }, { "id": "khavinson-2020", "type": "pubmed", "title": "Khavinson V et al. EDR peptide: possible mechanism of gene expression and protein synthesis regulation involved in the pathogenesis of Alzheimer's disease. Molecules 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33396470/", "pmid": "33396470", "year": 2020 }, { "id": "umnov-2013", "type": "pubmed", "title": "Umnov RS, Lin'kova NS, Khavinson VKh. Neuroprotective effects of peptide bioregulators in people of various age. Adv Gerontol 2013 (Russian language review)", "url": "https://pubmed.ncbi.nlm.nih.gov/24738258/", "pmid": "24738258", "year": 2013 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-pcac", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "epitalon", "thymalin", "semax", "p21" ], "cluster": "cognitive", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Pinealon peptide: evidence, side effects, legal status", "description": "What pinealon (Glu-Asp-Arg) is, what the rat and cell studies show, side effects, how it differs from epitalon, and its US legal status.", "h1": "Pinealon peptide", "headings": { "evidence": "Pinealon benefits: what the evidence shows", "safety": "Pinealon side effects" } } }, { "slug": "pt-141", "name": "PT-141 (bremelanotide)", "aliases": [ "Bremelanotide", "Vyleesi", "PT-141", "Bremelanotide acetate", "PT 141", "PT141", "PT-141 peptide", "PT 141 peptide" ], "class": "Cyclic heptapeptide melanocortin receptor agonist (MC4R and MC3R), an active metabolite of Melanotan II", "one_liner": "FDA approved (Vyleesi, 2019) for low sexual desire in premenopausal women; effect is small and nausea affects about 40% of users.", "summary": "PT-141 (bremelanotide) is a melanocortin receptor agonist approved by FDA in 2019 as Vyleesi, an on-demand subcutaneous injection for premenopausal women with acquired, generalized hypoactive sexual desire disorder. In the two RECONNECT phase 3 trials (1,267 women randomized), it raised the Female Sexual Function Index desire score by about 0.35 points more than placebo over 24 weeks, a statistically significant but small effect, with nausea in roughly 40% of users. Intranasal development for erectile dysfunction in men was stopped over blood pressure effects, so use in men is off-label and unsupported by an approved product.", "mechanism": "Bremelanotide activates melanocortin receptors, chiefly MC4R and to a lesser extent MC3R, in hypothalamic and other central circuits involved in sexual arousal and appetite. Unlike PDE5 inhibitors it acts centrally rather than on penile blood flow. Melanocortin activation also stimulates MC1R on melanocytes, which explains focal skin darkening, and produces transient increases in blood pressure and decreases in heart rate after each dose.", "evidence_grade": "human_rct", "evidence_summary": "Two identical 24 week randomized, double-blind, placebo-controlled phase 3 trials (RECONNECT, studies 301 and 302) in premenopausal women with hypoactive sexual desire disorder showed statistically significant increases in the FSFI desire domain (0.30 and 0.42 points versus placebo; integrated 0.35) and reductions in desire related distress (minus 0.37 and minus 0.29 on the FSDS-DAO item 13). Independent reanalysis has questioned the clinical meaningfulness of these effects. In men, small phase 1 and 2 studies of intranasal PT-141 showed erectile responses, including in sildenafil non-responders, but the nasal program was discontinued and no product is approved for men.", "human_evidence": "RECONNECT (Kingsberg 2019): 1,267 premenopausal women randomized 1:1 to bremelanotide 1.75 mg subcutaneously as needed or placebo for 24 weeks; sexual desire increased by 0.30 (study 301) and 0.42 (study 302) points versus placebo, and distress fell by 0.37 and 0.29 points; nausea, flushing, and headache each affected 10% or more of treated women. A 52 week open-label extension (Simon 2019) reported sustained effects and no new safety signals. Diamond 2004: double-blind, placebo-controlled intranasal PT-141 in healthy men and men with mild to moderate erectile dysfunction produced erectile responses. Safarinejad 2008: randomized, double-blind study in men who had failed sildenafil reported improved erectile function with intranasal bremelanotide. The nasal route was abandoned because of blood pressure increases.", "animal_evidence": "Rodent and primate studies established that melanocortin agonists including bremelanotide produce penile erection and increase female solicitation behaviors through central MC4R signaling. Rodent data also underlie the observed increases in blood pressure and decreases in food intake.", "conditions": [ "sexual-dysfunction" ], "literature_dosing": "FDA label (Vyleesi, DailyMed): 1.75 mg injected subcutaneously into the abdomen or thigh at least 45 minutes before anticipated sexual activity, no more than one dose in 24 hours and no more than eight doses per month. RECONNECT used the same regimen.", "routes": [ "Subcutaneous injection by autoinjector, on demand (Vyleesi)", "Intranasal (discontinued development program for men)", "Compounded subcutaneous vials and nasal sprays (not FDA approved formulations)" ], "side_effects": [ "Nausea (about 40% in trials, most often after the first dose; 13% needed an antiemetic)", "Flushing (about 20%)", "Injection site reactions (about 13%)", "Headache (about 11%)", "Vomiting, cough, fatigue, hot flush, paresthesia, dizziness, nasal congestion", "Transient increase in blood pressure (about 6 mmHg systolic and 3 mmHg diastolic) and decrease in heart rate peaking 2 to 4 hours after each dose", "Focal hyperpigmentation of the face, gums, or breasts (about 1%, more common with more than 8 doses per month, may not resolve)" ], "interactions": [ "Oral naltrexone: bremelanotide slows gastric emptying and significantly lowered naltrexone exposure; the label advises against use in people relying on oral naltrexone for opioid or alcohol use disorder", "Other oral drugs: absorption of drugs taken at the same time may be reduced (label cites indomethacin); separate dosing or monitor", "Antihypertensives: additive blood pressure effects are not expected but the transient pressor effect should be considered" ], "contraindications": [ "Uncontrolled hypertension or known cardiovascular disease", "Pregnancy (label advises effective contraception; discontinue if pregnant)", "Not indicated for postmenopausal women or men", "Not indicated for low desire due to a medical or psychiatric condition, a relationship problem, or a medication" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Vyleesi (bremelanotide injection) on June 21, 2019, for premenopausal women with acquired, generalized hypoactive sexual desire disorder. Because bremelanotide is the active ingredient of an approved drug, some 503A pharmacies compound it under the approved drug component pathway, but compounded PT-141 vials and nasal sprays are not FDA approved formulations, have not been tested for potency or sterility by FDA, and the nasal route was abandoned by the sponsor over blood pressure effects. Use in men is off-label.", "typical_cost": "Vyleesi retail cash prices run about 930 to 956 USD per carton of four autoinjectors; the manufacturer savings program lists 0 USD for most commercially insured patients and 99 USD per carton without coverage. Compounded PT-141 nasal spray through a licensed telehealth program is about 187 to 224 USD per month. Prices checked 2026-09-22 and change often.", "access_path": [ "Prescription from a licensed provider filled at a retail or specialty pharmacy as Vyleesi.", "Prescription filled by a 503A compounding pharmacy as compounded bremelanotide (not an FDA approved formulation).", "Telehealth clinics that prescribe compounded PT-141 for men or women off-label." ], "faqs": [ { "q": "What is PT-141 peptide?", "a": "PT-141 is the development code for bremelanotide, a synthetic peptide that activates melanocortin receptors in the brain involved in sexual desire. FDA approved it as Vyleesi, an injection used as needed by premenopausal women with acquired, generalized hypoactive sexual desire disorder. It is not approved for men.", "source_ids": [ "vyleesi-label", "kingsberg-2019" ] }, { "q": "Is PT-141 legal and FDA approved?", "a": "Yes, as Vyleesi. FDA approved bremelanotide injection in June 2019 for premenopausal women with acquired, generalized hypoactive sexual desire disorder. It is prescription only. Compounded PT-141 vials and nasal sprays sold by telehealth clinics are not FDA approved formulations, and use in men or postmenopausal women is off-label.", "source_ids": [ "vyleesi-label", "fda-compounding-qa" ] }, { "q": "Does PT-141 work for women with low libido?", "a": "It works a little. In the two RECONNECT trials (1,267 premenopausal women, 24 weeks), the FSFI desire score rose about 0.35 points more with bremelanotide than placebo and distress about low desire fell about 0.33 points more. Those differences were statistically significant, but an independent reanalysis argued they are too small to be clinically meaningful for most women, and about 40% of users had nausea.", "source_ids": [ "kingsberg-2019", "spielmans-2024" ] }, { "q": "Does PT-141 work for erectile dysfunction in men?", "a": "Small early studies of intranasal PT-141 showed erectile responses in healthy men and men with erectile dysfunction, including a randomized trial in men who had failed sildenafil. The sponsor stopped the nasal program because of blood pressure increases, and no product is approved for men. Any use in men today is off-label with compounded product and no approved dosing.", "source_ids": [ "diamond-2004", "safarinejad-2008", "vyleesi-label" ] }, { "q": "What are the side effects of PT-141?", "a": "Nausea is the main one, affecting about 40% of women in trials, usually after the first dose; about 13% needed an anti-nausea drug. Flushing (20%), injection site reactions (13%), and headache (11%) are common. Each dose transiently raises blood pressure by about 6 mmHg systolic and lowers heart rate, so it is contraindicated with uncontrolled hypertension or known cardiovascular disease. About 1% develop focal darkening of the face, gums, or breasts, which may be permanent.", "source_ids": [ "vyleesi-label", "kingsberg-2019" ] }, { "q": "What is the PT-141 (Vyleesi) dose on the FDA label?", "a": "The Vyleesi label dose is 1.75 mg injected under the skin of the abdomen or thigh with the prefilled autoinjector, as needed, at least 45 minutes before anticipated sexual activity. No more than one dose should be used in 24 hours, and more than 8 doses a month is not recommended. The label notes that how long each dose works is unknown. Compounded PT-141 vials and nasal sprays use the same peptide but are not FDA approved formulations and have no labeled dose.", "source_ids": [ "vyleesi-label" ] }, { "q": "How much does PT-141 cost?", "a": "Vyleesi costs about 930 to 956 USD cash for four autoinjectors, but the manufacturer savings program lists 0 USD for most commercially insured patients and 99 USD per carton for patients without coverage. Compounded PT-141 nasal spray through a licensed telehealth program is about 187 to 224 USD per month. Prices checked 2026-09-22.", "source_ids": [ "price-listing-vyleesi", "vyleesi-savings", "price-telehealth-pt141", "vyleesi-label" ] }, { "q": "Is PT-141 banned by WADA?", "a": "No. Bremelanotide is an approved medicine and is not named in any section of the WADA Prohibited List. Athletes should still check with their anti-doping organization, and note that compounded products may contain other substances.", "source_ids": [ "wada-list" ] }, { "q": "PT-141 vs Melanotan II: what is the difference?", "a": "PT-141 is a metabolite of Melanotan II with the same core structure but without the C-terminal amide. Melanotan II is a nonselective melanocortin agonist that tans skin and was never approved anywhere; it produced erections in two tiny crossover trials and was withdrawn from the FDA Category 2 compounding list in April 2026. PT-141 is more selective for MC4R, is FDA approved for women, and has large randomized trials. Neither is approved for men.", "source_ids": [ "kingsberg-2019", "fda-cat2" ] } ], "studies": [ { "pmid": "31599840", "title": "Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials (RECONNECT)", "year": 2019, "design": "Two identical randomized, double-blind, placebo-controlled trials, 24 weeks", "n": 1267, "population": "Premenopausal women with acquired, generalized hypoactive sexual desire disorder", "outcome": "FSFI desire domain increased 0.30 and 0.42 points versus placebo; distress (FSDS-DAO item 13) decreased 0.37 and 0.29 points versus placebo; nausea, flushing, and headache in 10% or more", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31599840/" }, { "pmid": "31599847", "title": "Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder", "year": 2019, "design": "52 week open-label extension of the RECONNECT trials", "population": "Premenopausal women who completed the double-blind phase", "outcome": "Improvements in desire and distress were maintained; no new safety signals", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/31599847/" }, { "pmid": "14963471", "title": "Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141 in healthy males and patients with mild-to-moderate erectile dysfunction", "year": 2004, "design": "Double-blind, placebo-controlled phase 1 and 2a studies of intranasal PT-141", "population": "Healthy men and men with mild to moderate erectile dysfunction", "outcome": "Intranasal PT-141 produced erectile responses measured by RigiScan; transient blood pressure effects noted", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/14963471/" }, { "pmid": "18206919", "title": "Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study", "year": 2008, "design": "Randomized, double-blind, placebo-controlled trial of intranasal bremelanotide", "population": "Men with erectile dysfunction who had not responded to sildenafil", "outcome": "Intranasal bremelanotide improved erectile function scores compared with placebo in sildenafil non-responders", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18206919/" }, { "pmid": "36809187", "title": "Small effects, questionable outcomes: bremelanotide for hypoactive sexual desire disorder", "year": 2024, "design": "Critical reanalysis of the phase 3 trial data", "population": "RECONNECT trial participants", "outcome": "Argues that the statistically significant changes in desire and distress are below thresholds for clinical meaningfulness", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36809187/" } ], "sources": [ { "id": "kingsberg-2019", "type": "pubmed", "title": "Kingsberg SA et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol 2019 (RECONNECT)", "url": "https://pubmed.ncbi.nlm.nih.gov/31599840/", "pmid": "31599840", "year": 2019 }, { "id": "simon-2019", "type": "pubmed", "title": "Simon JA et al. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder. Obstet Gynecol 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31599847/", "pmid": "31599847", "year": 2019 }, { "id": "diamond-2004", "type": "pubmed", "title": "Diamond LE et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141 in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/14963471/", "pmid": "14963471", "year": 2004 }, { "id": "safarinejad-2008", "type": "pubmed", "title": "Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18206919/", "pmid": "18206919", "year": 2008 }, { "id": "spielmans-2024", "type": "pubmed", "title": "Spielmans GI. Small effects, questionable outcomes: bremelanotide for hypoactive sexual desire disorder. J Sex Res 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/36809187/", "pmid": "36809187", "year": 2024 }, { "id": "vyleesi-label", "type": "fda", "title": "FDA prescribing information for Vyleesi (bremelanotide injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf", "year": 2025 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-listing-vyleesi", "type": "other", "title": "Published retail cash price listing for bremelanotide autoinjectors, accessed 2026-09-22", "url": "https://www.drugs.com/price-guide/vyleesi" }, { "id": "vyleesi-savings", "type": "other", "title": "Vyleesi (bremelanotide) manufacturer patient site, savings program terms, accessed 2026-09-22", "url": "https://vyleesi.com/" }, { "id": "price-telehealth-pt141", "type": "other", "title": "Licensed telehealth provider price page for compounded bremelanotide nasal spray, accessed 2026-09-22", "url": "https://www.agemd.com/sexual-health/pt-141-nasal-spray" } ], "related": [ "melanotan-ii", "melanotan-i", "kisspeptin-10", "oxytocin" ], "cluster": "sexual_health", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "PT-141 (Vyleesi): evidence, side effects, and legality", "description": "PT-141 peptide (bremelanotide, sold as Vyleesi): what it is, how well it works, side effects, the FDA label dose, cost, and use in men.", "h1": "PT-141 peptide (bremelanotide, Vyleesi)", "headings": { "evidence": "PT-141 benefits: what the evidence shows", "safety": "PT-141 side effects", "dosing": "PT-141 (Vyleesi) dose on the FDA label" } } }, { "slug": "kisspeptin-10", "name": "Kisspeptin-10", "aliases": [ "KP-10", "Metastin (45-54)", "Kisspeptin 10", "KISS1 decapeptide", "Kisspeptin", "Kisspeptin peptide", "Kisspeptin-10 peptide" ], "class": "Ten amino acid C-terminal fragment of kisspeptin (KISS1 gene product), an agonist at the kisspeptin receptor (KISS1R, formerly GPR54)", "one_liner": "Fragment of a brain hormone that raises LH and testosterone in small human studies; still on FDA's 503A Category 2 safety risk list, so it cannot be compounded.", "summary": "Kisspeptin-10 is the shortest active fragment of kisspeptin, the peptide from the hypothalamus (the brain's hormone control center) that drives release of GnRH, the master switch for reproductive hormones. Small placebo-controlled physiology studies in healthy men show it raises LH, FSH (the pituitary hormones that drive the testes and ovaries), and testosterone, and a 2026 study sustained those increases for 12 days with daily infusions, but no trial has tested a clinical outcome with kisspeptin-10 itself; the randomized trial in men with low sexual desire used the longer kisspeptin-54. FDA placed kisspeptin-10 on the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in September 2023 and it remains there as of April 2026, so it cannot be lawfully compounded, and it is prohibited in sport under WADA.", "mechanism": "Kisspeptin binds KISS1R on hypothalamic GnRH neurons and triggers pulsatile GnRH release, which in turn stimulates pituitary LH and FSH and downstream testosterone or estradiol. Kisspeptin-10 has the same receptor activity as full length kisspeptin-54 but a much shorter circulating half-life (minutes). Continuous exposure can desensitize the response, which is why chronic protocols use intermittent infusion. Kisspeptin also acts in limbic brain regions involved in sexual and emotional processing, the basis for its study in low sexual desire.", "evidence_grade": "human_observational", "evidence_summary": "Human data are small physiology studies from one academic group. Intravenous bolus kisspeptin-10 raised LH and FSH in healthy men at doses as low as 0.3 to 1 nmol/kg, raised gonadotropins in women only in the preovulatory phase, and had no effect in the follicular phase (n = 4 to 5 per group). A direct comparison in healthy men found kisspeptin-10, kisspeptin-54, and GnRH all stimulate gonadotropins. A 2026 randomized, single-blind, placebo-controlled study in 15 healthy men showed daily 8 hour subcutaneous infusions sustained LH, FSH, and testosterone increases for 12 days without receptor desensitization. No study has tested kisspeptin-10 for a clinical endpoint such as fertility, hypogonadism, or sexual function. The randomized study measured hormone levels in healthy men rather than a clinical endpoint; it is listed but does not raise the grade.", "human_evidence": "Jayasena 2011: intravenous bolus kisspeptin-10 increased serum LH and FSH in healthy men at 0.3 and 1.0 nmol/kg; in women no gonadotropin response occurred in the follicular phase at any dose or route, while LH and FSH rose in the preovulatory phase (n = 4 to 5 per group). Jayasena 2015: direct comparison of intravenous kisspeptin-10, kisspeptin-54, and GnRH in healthy men. Yeung 2026: in 15 healthy men, acute subcutaneous kisspeptin-10 infusions dose-dependently raised LH, FSH, and testosterone; continuous 5 day infusion at 180 nmol/h did not sustain gonadotropins, but daily 8 hour infusions at 150 nmol/h for 12 days did, and the receptor remained responsive afterward. The only randomized clinical trial in a patient population (Mills 2023, 32 men with hypoactive sexual desire disorder) used intravenous kisspeptin-54, not kisspeptin-10, and found increased sexual brain activation and penile tumescence.", "animal_evidence": "Kisspeptin-10 stimulates gonadotropin release in male and female rodents, sheep, and non-human primates through KISS1R on GnRH neurons; knockout of the receptor causes hypogonadotropic hypogonadism in mice and humans. Chronic continuous exposure in animals produces desensitization and suppression of the reproductive axis.", "conditions": [ "sexual-dysfunction" ], "literature_dosing": "Human physiology studies used intravenous bolus doses of 0.3 to 10 nmol/kg, subcutaneous bolus up to 32 nmol/kg, and intravenous infusion up to 720 pmol/kg/min (Jayasena 2011); subcutaneous infusions of 150 to 180 nmol/h for 8 hours daily or continuously (Yeung 2026). These were research protocols in healthy volunteers, not treatment regimens.", "routes": [ "Intravenous bolus or infusion (research studies)", "Subcutaneous bolus or pump infusion (research studies)", "Subcutaneous injection vials (as sold, not lawful for human use)" ], "side_effects": [ "No adverse effects reported in short research protocols in healthy volunteers", "Continuous exposure can suppress gonadotropin release (desensitization)", "No long-term human safety data", "FDA cites limited safety information and immunogenicity concerns for compounded product" ], "interactions": [ "No formal interaction studies exist", "Theoretical interaction with GnRH agonists and antagonists, testosterone, and other agents acting on the hypothalamic pituitary gonadal axis" ], "contraindications": [ "No approved indication; not for use outside research", "Pregnancy (kisspeptin is elevated in pregnancy but exogenous dosing has not been studied)", "Hormone sensitive cancers (theoretical, via sex steroid stimulation)", "Competitive athletes subject to WADA testing" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "FDA placed kisspeptin-10 on the 503A Category 2 list (substances that may present significant safety risks) on September 29, 2023, citing immunogenicity risk, peptide impurities, and no or limited safety information. As of the FDA page current to April 22, 2026, kisspeptin-10 remains in Category 2 and was not among the peptides withdrawn in April 2026 or taken up by the Pharmacy Compounding Advisory Committee in July 2026. It is not an FDA approved drug and a 503A pharmacy may not compound it.", "typical_cost": "Not available through licensed channels. Research chemical sellers list it, but those products are not lawful for human use and are not verified for purity.", "access_path": [ "Not legally available for human use in the United States outside a clinical trial.", "Not an FDA approved drug; on the FDA 503A Category 2 list.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is kisspeptin?", "a": "Kisspeptin is a natural hormone made in the hypothalamus, the brain's hormone control center, that switches on GnRH release, which in turn drives LH, FSH (the pituitary signals to the testes and ovaries), and sex hormone production. Kisspeptin-10 is its shortest active fragment and kisspeptin-54 is the longer circulating form; both are used in research studies. Neither is FDA approved, and kisspeptin-10 is on the FDA 503A Category 2 list (compounding ingredients flagged for significant safety risks), so it cannot be lawfully compounded.", "source_ids": [ "jayasena-2011", "jayasena-2015", "fda-cat2" ] }, { "q": "Is kisspeptin-10 legal in the United States?", "a": "No lawful route exists for human use. Kisspeptin-10 is not an approved drug, and FDA placed it on the 503A Category 2 list in September 2023, which means compounding pharmacies may not use it. As of April 2026 it is still in Category 2. Products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Does kisspeptin-10 increase testosterone?", "a": "In healthy men, yes, at least in the short term. Intravenous bolus doses raised LH and FSH within hours, and a 2026 study of 15 healthy men found daily 8 hour subcutaneous infusions sustained increases in LH, FSH, and testosterone for 12 days. Whether that translates to any clinical benefit in men with low testosterone has not been tested, and continuous exposure suppressed the response.", "source_ids": [ "jayasena-2011", "yeung-2026" ] }, { "q": "Does kisspeptin work for low libido?", "a": "The randomized trial that made headlines used kisspeptin-54, not kisspeptin-10. In 32 men with hypoactive sexual desire disorder, a 75 minute intravenous kisspeptin-54 infusion increased activation of sexual processing brain regions and penile tumescence compared with placebo. That was a single dose mechanistic study, not a treatment trial, and no study has tested kisspeptin-10 for sexual desire.", "source_ids": [ "mills-2023" ] }, { "q": "What are the side effects of kisspeptin-10?", "a": "In short research protocols in healthy volunteers no adverse effects were reported, but those studies were tiny and lasted hours to days. There are no long-term safety data. FDA lists immunogenicity risk and peptide impurities as concerns for compounded product, and continuous exposure can suppress rather than stimulate reproductive hormones.", "source_ids": [ "yeung-2026", "fda-cat2" ] }, { "q": "How is kisspeptin-10 taken?", "a": "Only by intravenous or subcutaneous infusion or bolus in research settings. Because its half-life is minutes, studies that wanted a sustained effect used pump infusions for 8 hours a day. There is no established treatment dose or schedule, and injection vials sold online have not been studied.", "source_ids": [ "jayasena-2011", "yeung-2026" ] }, { "q": "How much does kisspeptin-10 cost?", "a": "There is no licensed price because it cannot be lawfully dispensed. Research chemical listings exist but those products are not lawful for human use and are not tested for purity, so PeptideAgent does not report them as a cost of treatment.", "source_ids": [ "fda-cat2" ] }, { "q": "Is kisspeptin-10 banned by WADA?", "a": "Yes. It is not approved for human use anywhere, which places it in section S0 of the WADA Prohibited List, and as a releasing factor for LH it also falls under section S2 (peptide hormones and their releasing factors) in males. It is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "Kisspeptin-10 vs gonadorelin: which is better for keeping testosterone up on TRT?", "a": "Neither has a trial for that use. Gonadorelin is GnRH itself, which works only when delivered in pulses by a pump; kisspeptin-10 acts one step upstream and also needs intermittent dosing. Gonadorelin was the active ingredient of approved products and can be compounded; kisspeptin-10 is on the FDA Category 2 list and cannot. Both are prohibited for male athletes under WADA.", "source_ids": [ "yeung-2026", "fda-cat2", "wada-list" ] } ], "studies": [ { "pmid": "21976724", "title": "The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans", "year": 2011, "design": "Physiology study of intravenous and subcutaneous kisspeptin-10 versus vehicle", "population": "Healthy men and women (n = 4 to 5 per group)", "outcome": "LH and FSH rose in men at 0.3 to 1.0 nmol/kg intravenous bolus; no response in women in the follicular phase; response in the preovulatory phase", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/21976724/" }, { "pmid": "26089302", "title": "Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men", "year": 2015, "design": "Crossover physiology study", "population": "Healthy men", "outcome": "All three peptides stimulated LH and FSH; profiles of response differed by peptide", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26089302/" }, { "pmid": "42549827", "title": "Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men", "year": 2026, "design": "Randomized, single-blind, placebo-controlled physiology study in three parts", "n": 27, "population": "15 healthy men receiving kisspeptin-10 and 12 controls", "outcome": "Acute infusions dose-dependently raised LH, FSH, and testosterone; daily 8 hour infusions at 150 nmol/h sustained increases for 12 days; continuous infusion did not sustain gonadotropins", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42549827/" }, { "pmid": "36735255", "title": "Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial", "year": 2023, "design": "Double-blind, placebo-controlled, two-way crossover randomized trial of intravenous kisspeptin-54 (not kisspeptin-10)", "n": 32, "population": "Heterosexual men with hypoactive sexual desire disorder", "outcome": "Kisspeptin-54 modulated sexual processing brain activity (Cohen d 0.81) and increased penile tumescence by up to 56% more than placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36735255/" } ], "sources": [ { "id": "jayasena-2011", "type": "pubmed", "title": "Jayasena CN et al. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21976724/", "pmid": "21976724", "year": 2011 }, { "id": "jayasena-2015", "type": "pubmed", "title": "Jayasena CN et al. Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men. Hum Reprod 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26089302/", "pmid": "26089302", "year": 2015 }, { "id": "yeung-2026", "type": "pubmed", "title": "Yeung AC et al. Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men. Eur J Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42549827/", "pmid": "42549827", "year": 2026 }, { "id": "mills-2023", "type": "pubmed", "title": "Mills EG et al. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial. JAMA Netw Open 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36735255/", "pmid": "36735255", "year": 2023 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, sections S0 and S2", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "gonadorelin", "hcg", "pt-141", "oxytocin" ], "cluster": "sexual_health", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Kisspeptin: evidence, side effects, and legal status", "description": "What kisspeptin and kisspeptin-10 are, what the testosterone and libido studies show, side effects, and why it cannot be compounded in the US.", "h1": "Kisspeptin-10 (kisspeptin peptide)", "headings": { "evidence": "Kisspeptin benefits: what the evidence shows", "safety": "Kisspeptin side effects" } } }, { "slug": "oxytocin", "name": "Oxytocin", "aliases": [ "Pitocin", "Syntocinon", "Intranasal oxytocin", "OXT", "Compounded oxytocin nasal spray", "Oxytocin nasal spray", "Oxytocin peptide" ], "class": "Endogenous nine amino acid neuropeptide hormone (cyclic nonapeptide) produced in the hypothalamus and released from the posterior pituitary", "one_liner": "FDA approved injectable (Pitocin) for labor and postpartum bleeding; intranasal use for bonding, libido, or autism rests on small, mixed trials.", "summary": "Oxytocin is a natural nonapeptide hormone approved by FDA for decades as an injection (Pitocin) to induce or augment labor and control postpartum bleeding, where its efficacy is established. The intranasal oxytocin sold by compounding pharmacies for sexual function, bonding, or social anxiety is not an FDA approved product, and randomized trials of nasal oxytocin show small and inconsistent effects: in 29 healthy couples a 24 IU dose did not change sexual drive, arousal, or erection but modestly increased orgasm intensity and post-sex contentment, and meta-analyses in autism find small effects on social functioning at best. It is not prohibited by WADA.", "mechanism": "Oxytocin binds the oxytocin receptor, a G protein coupled receptor on uterine smooth muscle (contraction), mammary myoepithelial cells (milk ejection), and neurons in limbic and hypothalamic regions involved in social bonding, trust, sexual behavior, and stress regulation. Peripheral oxytocin crosses the blood brain barrier poorly; intranasal delivery is proposed to reach the brain through olfactory and trigeminal pathways, though how much reaches central receptors in humans is debated. Its half-life in plasma is a few minutes.", "evidence_grade": "human_rct", "evidence_summary": "For obstetric use, oxytocin is standard of care with decades of trial and label evidence for labor induction, augmentation, and prevention of postpartum hemorrhage. For the off-label uses that drive peptide clinic interest the evidence is thin: one double-blind crossover study in 29 healthy couples found intranasal oxytocin 24 IU had no effect on classical sexual function measures but small to moderate effects on orgasm intensity and post-sex contentment, larger in men. A 2021 multilevel meta-analysis of 28 studies (726 participants) in autism reported beneficial effects on social functioning but not on non-social symptoms, and later meta-analyses of randomized trials describe small and inconsistent results across mental disorders. No randomized trial supports nasal oxytocin for erectile dysfunction, low libido as a diagnosis, or relationship problems.", "human_evidence": "Behnia 2014: 29 heterosexual couples (58 participants), double-blind placebo-controlled crossover, intranasal oxytocin 24 IU before sexual intercourse; no change in sexual drive, arousal, erection, or lubrication; increased orgasm intensity and contentment after intercourse, more pronounced in men, with small to moderate effect sizes. Huang 2021: multilevel meta-analysis of 28 studies (n = 726) of oxytocin in autism spectrum disorder reporting benefit on social functioning but not on non-social symptoms. Labor and postpartum hemorrhage indications rest on the Pitocin label and long standing obstetric trial evidence.", "animal_evidence": "Rodent and vole studies established oxytocin's role in maternal behavior, pair bonding, social recognition, and sexual behavior; oxytocin receptor knockout mice show deficits in social memory. Rat studies show central oxytocin facilitates erection and ejaculation. This animal work motivated the human intranasal trials but does not translate directly to dosing or efficacy in people.", "conditions": [ "sexual-dysfunction" ], "literature_dosing": "FDA label (Pitocin, DailyMed; hospital use): induction or stimulation of labor by intravenous infusion only, starting at 0.5 to 1 milliunit per minute and increasing by 1 to 2 milliunits per minute every 30 to 60 minutes until the desired contraction pattern is established, using an infusion pump; control of postpartum bleeding, 10 to 40 units added to a running intravenous infusion (maximum 40 units per 1,000 mL) or 10 units intramuscularly after delivery of the placenta. The label states Pitocin is not indicated for elective induction of labor. No FDA label gives an intranasal dose or any dose for sexual function, social behavior, or weight.", "routes": [ "Intravenous infusion or intramuscular injection (Pitocin, approved)", "Intranasal spray (compounded or imported; not FDA approved in the United States)", "Sublingual and oral lozenges (compounded; no absorption data)" ], "side_effects": [ "Injectable in obstetrics: uterine hyperstimulation, uterine rupture, fetal bradycardia and distress, postpartum hemorrhage, arrhythmias, anaphylaxis", "Water intoxication with hyponatremia and seizures after prolonged high dose infusion (antidiuretic effect)", "Hypotension and reflex tachycardia after rapid intravenous bolus", "Boxed warning on Pitocin: not for elective induction of labor", "Intranasal: nasal irritation, headache, drowsiness, transient dizziness; long term safety of repeated nasal dosing is not established" ], "interactions": [ "Vasoconstrictors and sympathomimetics: severe hypertension reported when oxytocin is given after vasoconstrictors, especially with caudal block anesthesia", "Cyclopropane anesthesia: maternal hypotension and bradycardia", "Prostaglandins and other uterotonics: additive uterine stimulation", "Intranasal oxytocin: no formal interaction studies" ], "contraindications": [ "Pitocin label: significant cephalopelvic disproportion, unfavorable fetal positions, obstetric emergencies favoring surgery, fetal distress when delivery is not imminent, hypertonic uterine patterns, hypersensitivity, and situations where vaginal delivery is contraindicated", "Intranasal oxytocin: pregnancy (uterotonic), breastfeeding without medical supervision, uncontrolled hypotension" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "Oxytocin injection is FDA approved (Pitocin and generics) for obstetric indications. Because oxytocin is the active ingredient of an approved drug, 503A pharmacies may compound it in other dosage forms such as nasal sprays or lozenges for individual prescriptions; these compounded products are not FDA approved, have no approved indication, and have not been shown to achieve meaningful brain levels. Oxytocin is a 9 amino acid peptide and was not among the products transitioned to biologic status in March 2020, so it remains eligible for compounding. No intranasal oxytocin product is FDA approved in the United States.", "typical_cost": "Generic oxytocin injection costs about 1.52 to 4.37 USD per vial in a published cash listing and is used in hospitals. Compounded oxytocin nasal spray through licensed telehealth programs runs about 115 to 135 USD per month. Prices checked 2026-09-22.", "access_path": [ "Prescription injectable used in hospitals and clinics for labor and postpartum care.", "Prescription filled by a 503A compounding pharmacy as a nasal spray or lozenge (not an FDA approved formulation).", "Telehealth and peptide clinics prescribing compounded intranasal oxytocin off-label." ], "faqs": [ { "q": "Is oxytocin (Pitocin) FDA approved, and what is it used for?", "a": "Yes, as an injection for obstetric use. Before delivery, the Pitocin label covers starting or improving uterine contractions for medical reasons, such as induction of labor with a medical indication, stimulation of labor in selected cases of uterine inertia, and as adjunctive therapy in incomplete or inevitable abortion. After delivery, it covers producing uterine contractions in the third stage of labor and controlling postpartum bleeding. It is not indicated for elective induction. No oxytocin nasal spray or lozenge is FDA approved; those are compounded.", "source_ids": [ "pitocin-label", "fda-compounding-qa" ] }, { "q": "Does intranasal oxytocin improve sex or libido?", "a": "Not by much, based on the one controlled study. In 29 healthy couples, 24 IU of nasal oxytocin before sex did not change sexual drive, arousal, erection, or lubrication. It modestly increased reported orgasm intensity and contentment afterward, more so in men, with small to moderate effect sizes. No trial has tested it in people with a diagnosed sexual disorder.", "source_ids": [ "behnia-2014" ] }, { "q": "Does oxytocin work for autism or social anxiety?", "a": "The evidence is mixed. A 2021 multilevel meta-analysis of 28 studies (726 participants) with autism reported a beneficial effect on social functioning but not on non-social symptoms, and many individual randomized trials, including large ones, found no benefit. No regulator has approved oxytocin for autism or anxiety. PeptideAgent treats these uses as unproven.", "source_ids": [ "huang-2021" ] }, { "q": "What are the side effects of oxytocin?", "a": "For the injectable in labor: uterine overstimulation, fetal distress, uterine rupture, arrhythmias, and, with prolonged high doses, water retention with dangerously low sodium. Pitocin carries a boxed warning against elective induction. Nasal oxytocin in trials mainly caused nasal irritation, headache, and drowsiness, but there is no long-term safety data for repeated home use.", "source_ids": [ "pitocin-label", "behnia-2014" ] }, { "q": "What is the oxytocin (Pitocin) dose on the FDA label?", "a": "For labor, an intravenous infusion started at 0.5 to 1 milliunit per minute and raised by 1 to 2 milliunits per minute every 30 to 60 minutes until contractions are adequate. For bleeding after delivery, 10 to 40 units added to an intravenous infusion (no more than 40 units per liter) or 10 units into muscle after the placenta is delivered. These are hospital doses; no label covers intranasal use, and research doses from intranasal studies are not label doses.", "source_ids": [ "pitocin-label" ] }, { "q": "How much does oxytocin cost?", "a": "Generic oxytocin injection is inexpensive, about 1.52 to 4.37 USD per vial in a published cash listing, and is administered in hospitals. Compounded oxytocin nasal spray through licensed telehealth programs costs about 115 to 135 USD per month. Prices checked 2026-09-22.", "source_ids": [ "price-listing-oxytocin", "price-telehealth-oxytocin-a", "price-telehealth-oxytocin-b", "pitocin-label" ] }, { "q": "Is oxytocin banned by WADA?", "a": "No. Oxytocin is not named in any section of the WADA Prohibited List, and as an approved medicine it does not fall under S0. Athletes should still check with their anti-doping organization about compounded products.", "source_ids": [ "wada-list" ] }, { "q": "Oxytocin vs PT-141 for low libido: which has better evidence?", "a": "PT-141 (bremelanotide) has two large randomized trials and an FDA approval for low sexual desire in premenopausal women, although its effect is small and nausea is common. Intranasal oxytocin has one small crossover study in healthy couples showing no effect on desire or arousal. For a diagnosed desire disorder, PT-141 is the only one with an approved indication.", "source_ids": [ "behnia-2014", "pitocin-label" ] } ], "studies": [ { "pmid": "24503174", "title": "Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples", "year": 2014, "design": "Double-blind, placebo-controlled crossover study of intranasal oxytocin 24 IU in a naturalistic home setting", "n": 58, "population": "29 healthy heterosexual couples", "outcome": "No change in sexual drive, arousal, erection, or lubrication; increased orgasm intensity and post-intercourse contentment, more pronounced in men; small to moderate effect sizes", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/24503174/" }, { "pmid": "33400920", "title": "Intranasal oxytocin in the treatment of autism spectrum disorders: a multilevel meta-analysis", "year": 2021, "design": "Multilevel meta-analysis of randomized and uncontrolled studies", "n": 726, "population": "Children and adults with autism spectrum disorder across 28 studies", "outcome": "Beneficial effect on social functioning; no strong evidence of improvement in non-social symptoms", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33400920/" } ], "sources": [ { "id": "behnia-2014", "type": "pubmed", "title": "Behnia B et al. Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples. Horm Behav 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24503174/", "pmid": "24503174", "year": 2014 }, { "id": "huang-2021", "type": "pubmed", "title": "Huang Y et al. Intranasal oxytocin in the treatment of autism spectrum disorders: a multilevel meta-analysis. Neurosci Biobehav Rev 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33400920/", "pmid": "33400920", "year": 2021 }, { "id": "pitocin-label", "type": "fda", "title": "FDA prescribing information for Pitocin (oxytocin injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6e5a66fc-e507-497c-b5ce-44a8c95898ad", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-listing-oxytocin", "type": "other", "title": "Published retail cash price listing for generic oxytocin injection, accessed 2026-09-22", "url": "https://www.drugs.com/price-guide/oxytocin" }, { "id": "price-telehealth-oxytocin-a", "type": "other", "title": "Licensed telehealth provider price page for compounded oxytocin nasal spray, accessed 2026-09-22", "url": "https://getheally.com/patients/oxytocin-prescription" }, { "id": "price-telehealth-oxytocin-b", "type": "other", "title": "Second licensed telehealth provider price page for compounded oxytocin nasal spray, accessed 2026-09-22", "url": "https://tryinvigor.com/plans/buy-oxytocin-nasal-spray/" } ], "related": [ "pt-141", "kisspeptin-10", "vasopressin", "desmopressin" ], "cluster": "sexual_health", "last_verified": "2026-09-23", "review_status": "draft", "version": 4, "seo": { "title": "Oxytocin (Pitocin): uses, side effects, and dosing", "description": "Pitocin is oxytocin, given by IV in hospital to start or strengthen labor and control bleeding after birth. FDA label uses and doses, and nasal spray claims.", "h1": "Oxytocin (Pitocin)" } }, { "slug": "melanotan-ii", "name": "Melanotan II", "aliases": [ "MT-II", "MT2", "Melanotan 2", "Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2", "Barbie peg (slang)", "Tanning peptide", "Melanotan", "MT2 peptide", "MT-2", "Melanotan 2 peptide" ], "class": "Synthetic cyclic heptapeptide analog of alpha-melanocyte stimulating hormone; nonselective melanocortin receptor agonist (MC1R, MC3R, MC4R, MC5R)", "one_liner": "Unapproved tanning and libido injection with two tiny 1990s erection trials, case reports of melanoma and prolonged erections, and no lawful source.", "summary": "Melanotan II is a ring-shaped, lab-made version of alpha-MSH, the hormone that tells skin to make pigment, developed at the University of Arizona in the 1980s; it darkens skin, causes erections, and suppresses appetite by activating several melanocortin receptors at once. It was never approved anywhere; the only human trials are two double-blind crossover studies (each man got both drug and placebo without knowing which) of 10 men each from 1998 and 2000 showing erections after a single injection under the skin, with frequent nausea and yawning, and its selective metabolite (breakdown product) became the approved drug bremelanotide instead. FDA placed it on the 503A Category 2 compounding list (ingredients flagged for significant safety risks) citing case reports of melanoma (skin cancer), posterior reversible encephalopathy syndrome (brain swelling), sympathomimetic toxidrome (an overstimulation reaction), and priapism (a painful erection that will not go away), and the nomination was withdrawn in April 2026, so it has no lawful route to patients.", "mechanism": "Melanotan II is a superpotent, nonselective agonist at melanocortin receptors. MC1R activation on melanocytes increases eumelanin synthesis and produces tanning without UV exposure, along with darkening of existing moles. MC4R and MC3R activation in the hypothalamus produces penile erection, increased sexual desire, reduced appetite, and stretching and yawning. Off target and receptor mediated effects on blood pressure and heart rate are documented in its metabolite bremelanotide.", "evidence_grade": "human_rct", "evidence_summary": "Two small double-blind, placebo-controlled crossover trials from the developing group in the 1990s. In 10 men with psychogenic erectile dysfunction, 0.025 mg/kg subcutaneously produced clinically apparent erections in 8 of 10, with mean tip rigidity above 80% lasting 38 minutes versus 3 minutes for placebo. In 10 men with organic erectile dysfunction, erections followed 12 of 19 injections versus 1 of 21 placebo doses, sexual desire increased, and severe nausea followed 4 of 19 injections. The only tanning data come from a 1996 pilot phase I study in 3 men, 2 of whom developed measurably darker skin, and the published human safety literature since then consists of case reports of harm.", "human_evidence": "Dorr 1996: single-blind, placebo-controlled pilot phase I study in 3 healthy men; 2 had increased pigmentation of the face, upper body, and buttock 1 week after a short course of injections, with mild nausea, yawning and stretching, and spontaneous erections. Wessells 1998: double-blind, placebo-controlled crossover, 10 men with psychogenic erectile dysfunction, Melanotan II 0.025 mg/kg subcutaneously; erections in 8 of 10, mean duration of tip rigidity above 80% of 38.0 minutes versus 3.0 minutes with placebo (p = 0.0045); nausea, stretching and yawning, and decreased appetite more frequent than placebo. Wessells 2000: same design in 10 men with organic risk factors; erections after 12 of 19 injections versus 1 of 21 placebo doses, mean rigidity score 6.9 of 10 in responders, higher sexual desire, and severe nausea after 4 of 19 injections. Case reports since: melanoma in a 20 year old woman who combined it with sunbed tanning (2014), eruptive naevi and darkening of existing naevi within 24 hours of a single injection (2014), priapism requiring treatment (2019), renal infarction (2020), and oral mucosal pigment changes (2026). FDA also cites reports of melanoma, posterior reversible encephalopathy syndrome, and sympathomimetic toxidrome.", "animal_evidence": "Melanotan II induces skin darkening in frogs, mice, and guinea pigs and penile erection and grooming behaviors in rats through central melanocortin receptors. Rodent studies also show reduced food intake and body weight through MC4R, work that later informed setmelanotide and bremelanotide development.", "conditions": [ "sexual-dysfunction" ], "literature_dosing": "The two human trials used a single subcutaneous dose of 0.025 mg/kg given on separate occasions. No repeat dose, tanning, or dose finding study has been published; the loading and maintenance schedules described by sellers have no literature basis.", "routes": [ "Subcutaneous injection (trials and as sold)", "Nasal spray (as sold; no studies)", "Products labeled research use only are not lawful for human use" ], "side_effects": [ "Nausea, sometimes severe (4 of 19 injections in the 2000 trial)", "Stretching and yawning, flushing, decreased appetite", "Spontaneous erections and priapism (case report requiring intervention)", "Darkening of existing moles and eruptive new naevi, sometimes within 24 hours of one dose", "Melanoma reported in association with use (causality not established; FDA cites published case reports)", "Posterior reversible encephalopathy syndrome and sympathomimetic toxidrome (FDA cited case reports)", "Renal infarction (case report)", "Rhabdomyolysis and infections from unsterile injection products reported in the case literature" ], "interactions": [ "No formal interaction studies exist", "Additive blood pressure and heart rate effects with sympathomimetics are plausible based on its metabolite bremelanotide", "PDE5 inhibitors: combined use has not been studied with Melanotan II and priapism risk may increase" ], "contraindications": [ "Personal or family history of melanoma or many atypical moles", "Cardiovascular disease or uncontrolled hypertension (based on bremelanotide data)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited at all times under S0)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Melanotan II was placed on the FDA 503A Category 2 list (substances that may present significant safety risks) with FDA citing immunogenicity risk, peptide impurities, and published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome, and priapism. As of the FDA page current to April 22, 2026, its nomination has been withdrawn, so it no longer sits in Category 2, but it is not on the 503A bulks list, was not among the peptides the Pharmacy Compounding Advisory Committee took up in July 2026, and is not a component of any approved drug. A 503A pharmacy therefore has no basis to compound it. It is not approved as a drug in any country.", "typical_cost": "Not available through licensed channels. Gray market vials are sold online for tanning, but those products are not lawful for human use and have been found unsterile or mislabeled.", "access_path": [ "Not legally available for human use in the United States.", "Not an FDA approved drug and not compoundable under 503A or 503B.", "Products sold online as tanning injections or nasal sprays are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "What is the tanning peptide called?", "a": "The injection sold as the tanning peptide is usually melanotan II, also called MT2 or MT-II. It is a synthetic copy of alpha-MSH, the hormone that tells skin cells to make melanin (skin pigment). Its relative melanotan I (afamelanotide) is FDA approved only as an implant for erythropoietic protoporphyria, a rare disease that makes light exposure painful, not for cosmetic tanning. Melanotan II is not approved anywhere and has no lawful source in the United States.", "source_ids": [ "dorr-1996", "scenesse-label", "fda-cat2" ] }, { "q": "Is Melanotan II legal in the United States?", "a": "There is no lawful route to obtain it for human use. It is not an approved drug in any country, FDA listed it in Category 2 of the 503A compounding program because of safety case reports, and the nomination was withdrawn in April 2026 rather than advanced. It is sold online as a tanning injection, and those sales are unlawful drug marketing. Possession itself is not a criminal matter.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Does Melanotan II work for erectile dysfunction?", "a": "In two very small crossover trials, yes: a single injection produced erections in 8 of 10 men with psychogenic erectile dysfunction and after 12 of 19 injections in men with organic erectile dysfunction, along with increased sexual desire. The trade-off was nausea, sometimes severe, and yawning. Its selective metabolite, bremelanotide, was developed instead and is the approved product.", "source_ids": [ "wessells-1998", "wessells-2000" ] }, { "q": "Does Melanotan II give you a tan?", "a": "Yes. It darkens skin by stimulating melanin production through the MC1R receptor. A 1996 pilot study in 3 men measured darker skin in 2 of them after a short course, and no larger tanning trial has been done. The same mechanism darkens existing moles and can trigger eruptive new naevi within a day of a single dose, which complicates skin cancer surveillance, and FDA cites case reports of melanoma in users.", "source_ids": [ "dorr-1996", "schulze-2014", "fda-cat2" ] }, { "q": "Does melanotan 2 work without sun?", "a": "Partly. In the 1996 pilot study, 2 of 3 men had measurably darker skin on the face, upper body, and buttock a week after dosing ended, including skin that is rarely sun exposed, because the peptide stimulates pigment cells directly. The study was tiny and did not control sun exposure, and users commonly add sun or sunbeds, which adds ultraviolet damage on top. A published melanoma case followed melanotan II combined with sunbed tanning.", "source_ids": [ "dorr-1996", "hjuler-2014" ] }, { "q": "How does Melanotan II work?", "a": "It is a cyclic, long acting copy of alpha-MSH that switches on several melanocortin receptors at once. The receptor on skin pigment cells drives tanning, while receptors in the brain drive erections, sexual desire, reduced appetite, and the yawning and nausea seen in trials. That lack of selectivity is why a more selective relative, bremelanotide, became the approved drug instead. No human half-life study of melanotan II has been published.", "source_ids": [ "dorr-1996", "wessells-1998" ] }, { "q": "What are the side effects of Melanotan II?", "a": "In trials: nausea (severe after 4 of 19 injections), stretching and yawning, flushing, loss of appetite, and spontaneous erections. In case reports: priapism needing emergency treatment, eruptive and darkening moles, melanoma after use with sunbeds, renal infarction, and mouth pigment changes. FDA additionally cites melanoma, posterior reversible encephalopathy syndrome, and sympathomimetic toxidrome. Unsterile gray market vials add infection risk.", "source_ids": [ "wessells-2000", "dreyer-2019", "hjuler-2014", "peters-2020", "fda-cat2" ] }, { "q": "How is Melanotan II taken?", "a": "The trials gave single subcutaneous injections under medical supervision. Sellers describe loading phases and maintenance injections or nasal sprays for tanning that have never been studied, and no repeat dose safety data exist. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "wessells-1998", "dorr-1996" ] }, { "q": "How much does Melanotan II cost?", "a": "There is no licensed price because it cannot be lawfully dispensed. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-cat2" ] }, { "q": "Is Melanotan II banned by WADA?", "a": "Yes. Melanotan II has no approval from any government health authority, which places it in section S0 (non-approved substances) of the WADA Prohibited List. It is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "Melanotan II vs Melanotan I: what is the difference?", "a": "Melanotan I (afamelanotide) is a linear analog selective for MC1R, approved by FDA in 2019 as a subcutaneous implant for the rare light sensitivity disease erythropoietic protoporphyria; it tans but does not cause erections or nausea to the same degree. Melanotan II is a cyclic, nonselective analog that hits MC3R and MC4R too, which is why it affects libido and appetite, and it was never approved. Only afamelanotide has a lawful route, and only for its approved indication.", "source_ids": [ "wessells-2000", "fda-cat2" ] } ], "studies": [ { "pmid": "9679884", "title": "Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study", "year": 1998, "design": "Double-blind, placebo-controlled crossover trial with RigiScan monitoring, single 0.025 mg/kg subcutaneous dose", "n": 10, "population": "Men with erectile dysfunction of no known organic cause", "outcome": "Erections in 8 of 10 men; tip rigidity above 80% for 38.0 minutes versus 3.0 minutes with placebo (p = 0.0045); nausea, stretching, yawning, and decreased appetite more frequent", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9679884/" }, { "pmid": "11018622", "title": "Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction", "year": 2000, "design": "Double-blind, placebo-controlled crossover trial, two doses each of Melanotan II 0.025 mg/kg and vehicle", "n": 10, "population": "Men with erectile dysfunction and organic risk factors", "outcome": "Erections after 12 of 19 injections versus 1 of 21 placebo doses; tip rigidity above 80% for 45.3 versus 1.9 minutes; higher sexual desire; severe nausea after 4 of 19 injections", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/11018622/" }, { "pmid": "24334249", "title": "Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose injection of melanotan II", "year": 2014, "design": "Case report", "population": "One adult user", "outcome": "Eruptive new naevi and darkening of existing naevi within 24 hours of a single injection", "grade": "anecdotal", "url": "https://pubmed.ncbi.nlm.nih.gov/24334249/" }, { "pmid": "30796078", "title": "Melanotan-induced priapism: a hard-earned tan", "year": 2019, "design": "Case report", "population": "One adult user", "outcome": "Priapism after melanotan use requiring medical intervention", "grade": "anecdotal", "url": "https://pubmed.ncbi.nlm.nih.gov/30796078/" }, { "pmid": "31953620", "title": "Melanotan II: a possible cause of renal infarction: review of the literature and case report", "year": 2020, "design": "Case report with literature review", "population": "One adult user", "outcome": "Renal infarction temporally associated with Melanotan II use", "grade": "anecdotal", "url": "https://pubmed.ncbi.nlm.nih.gov/31953620/" }, { "pmid": "8637402", "title": "Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study", "year": 1996, "design": "Single-blind, placebo-controlled pilot phase I study (alternating injection days)", "n": 3, "population": "Healthy men", "outcome": "Increased pigmentation of the face, upper body, and buttock in 2 of 3 subjects 1 week after dosing ended; mild nausea, yawning and stretching, and spontaneous erections", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/8637402/" } ], "sources": [ { "id": "wessells-1998", "type": "pubmed", "title": "Wessells H et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9679884/", "pmid": "9679884", "year": 1998 }, { "id": "wessells-2000", "type": "pubmed", "title": "Wessells H et al. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology 2000", "url": "https://pubmed.ncbi.nlm.nih.gov/11018622/", "pmid": "11018622", "year": 2000 }, { "id": "schulze-2014", "type": "pubmed", "title": "Schulze F et al. Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose injection of melanotan II. Eur J Dermatol 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24334249/", "pmid": "24334249", "year": 2014 }, { "id": "dreyer-2019", "type": "pubmed", "title": "Dreyer BA et al. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30796078/", "pmid": "30796078", "year": 2019 }, { "id": "peters-2020", "type": "pubmed", "title": "Peters B et al. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31953620/", "pmid": "31953620", "year": 2020 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "dorr-1996", "type": "pubmed", "title": "Dorr RT et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996", "url": "https://pubmed.ncbi.nlm.nih.gov/8637402/", "pmid": "8637402", "year": 1996 }, { "id": "hjuler-2014", "type": "pubmed", "title": "Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24355990/", "pmid": "24355990", "year": 2014 }, { "id": "scenesse-label", "type": "fda", "title": "FDA prescribing information for Scenesse (afamelanotide) implant, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=scenesse", "year": 2025 } ], "related": [ "melanotan-i", "pt-141", "kisspeptin-10" ], "cluster": "sexual_health", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Melanotan II (MT2): tanning peptide risks and legality", "description": "Melanotan II, the MT2 tanning peptide: whether it works without sun, side effects including moles and melanoma reports, and why it has no lawful source.", "h1": "Melanotan II (MT2 tanning peptide)", "headings": { "evidence": "Melanotan II benefits: what the evidence shows", "safety": "Melanotan II side effects" } } }, { "slug": "melanotan-i", "name": "Melanotan I (afamelanotide)", "aliases": [ "Afamelanotide", "Scenesse", "MT-I", "MT1", "[Nle4, D-Phe7]-alpha-MSH", "CUV1647", "Melanotan 1", "Melanotan-1", "MT-1" ], "class": "Synthetic linear 13 amino acid analog of alpha-melanocyte stimulating hormone, selective MC1R agonist, delivered as a subcutaneous implant", "one_liner": "FDA approved implant (Scenesse, 2019) that lets people with erythropoietic protoporphyria tolerate sunlight; not approved or sold for tanning.", "summary": "Melanotan I is the original alpha-MSH analog, now the FDA approved drug afamelanotide (Scenesse), a 16 mg subcutaneous implant approved in October 2019 to increase pain-free light exposure in adults with the rare photosensitivity disorder erythropoietic protoporphyria. In two randomized placebo-controlled trials it increased median pain-free direct sunlight exposure from 40.8 to 69.4 hours over 6 months (US, n = 94) and from 0.8 to 6.0 hours over 9 months (EU, n = 74), with mostly mild adverse events. It is available only through specialist centers and is not approved or lawfully sold for cosmetic tanning; the injectable Melanotan I sold online is an unapproved product.", "mechanism": "Afamelanotide is a potent, long acting agonist at the melanocortin 1 receptor on melanocytes. MC1R activation increases eumelanin production and melanocyte proliferation, which darkens skin and provides a photoprotective pigment barrier without UV exposure; it also has anti-inflammatory and antioxidant effects in skin cells. Unlike Melanotan II it has little activity at MC3R and MC4R, so it does not meaningfully affect sexual function or appetite.", "evidence_grade": "human_rct", "evidence_summary": "Two multicenter randomized, double-blind, placebo-controlled trials of 16 mg implants every 60 days in adults with erythropoietic protoporphyria (Langendonk 2015). In the US trial (94 patients, 3 implants, 180 days) median pain-free direct sunlight exposure was 69.4 hours with afamelanotide versus 40.8 hours with placebo (p = 0.04). In the EU trial (74 patients, 5 implants, 270 days) it was 6.0 versus 0.8 hours (p = 0.005) and phototoxic reactions fell from 146 to 77. Quality of life improved in both trials; adverse events were mostly mild. Long-term observational registries support continued use under dermatologic surveillance.", "human_evidence": "Langendonk 2015 (NEJM): US study, 94 patients randomized 1:1 to afamelanotide or placebo implants every 60 days for 180 days; median pain-free sun exposure 69.4 versus 40.8 hours. EU study, 74 patients for 270 days; median 6.0 versus 0.8 hours of pain-free exposure, 77 versus 146 phototoxic reactions, improved quality of life. Serious adverse events were not attributed to the drug. Earlier phase 2 work and European post-marketing data (EU approval 2014) informed the FDA approval in 2019.", "animal_evidence": "Afamelanotide induces pigmentation in mice and guinea pigs and reduces UV induced DNA damage and inflammation in animal and human skin models. Melanocortin 1 receptor selectivity was established in receptor binding and cell assays.", "conditions": [ "skin-aging" ], "literature_dosing": "FDA label (Scenesse, DailyMed): one implant containing 16 mg of afamelanotide inserted subcutaneously above the anterior supra-iliac crest every 2 months by a healthcare professional who has completed the manufacturer's implantation training, with sun and light protection maintained during treatment. The label covers only adults with a history of phototoxic reactions from erythropoietic protoporphyria; no dose is established for tanning or any cosmetic use.", "routes": [ "Subcutaneous controlled release implant inserted by a trained provider (Scenesse)", "Injectable Melanotan I vials sold online are unapproved products and not the approved dosage form" ], "side_effects": [ "Implant site reactions (pain, bruising, redness, pruritus, and rarely implant expulsion)", "Nausea, headache, fatigue, dizziness, nasopharyngitis, back pain, upper respiratory infection", "Skin hyperpigmentation, darkening of existing moles, new naevi and freckles", "Label recommends full body skin examination twice yearly and monitoring of existing lesions", "Long-term skin cancer risk not fully characterized; melanoma has not been shown to be caused by afamelanotide in registries but surveillance is required" ], "interactions": [ "No formal drug interaction studies (label states none identified)", "Theoretical additive pigmentation with other melanocortin agonists" ], "contraindications": [ "Label lists no absolute contraindications", "Not studied in pregnancy or breastfeeding", "Not studied in children (approved for adults)", "Not indicated or approved for tanning or any cosmetic purpose" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Scenesse (afamelanotide) implant on October 8, 2019, for adults with a history of phototoxic reactions from erythropoietic protoporphyria; the European Medicines Agency approved it in 2014. It is dispensed only through certified specialist centers because insertion requires training. Afamelanotide is not on any 503A or 503B bulks list; as the active ingredient of an approved drug it could in principle be compounded in another dosage form, but injectable Melanotan I sold online for tanning is not a compounded prescription product and is marketed unlawfully.", "typical_cost": "Specialty orphan drug priced in the tens of thousands of USD per implant before insurance, with several implants per year; insurance and manufacturer support programs determine out of pocket cost for approved patients. It is not sold for cosmetic use. Gray market Melanotan I vials are not lawful for human use and are not verified for purity.", "access_path": [ "Prescription from a specialist in erythropoietic protoporphyria at a certified treatment center (Scenesse implant).", "Not available for tanning or cosmetic use through any licensed channel.", "Products sold online as Melanotan I injections are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is Melanotan I legal and FDA approved?", "a": "As afamelanotide (Scenesse), yes. FDA approved it in October 2019 as an implant for adults with erythropoietic protoporphyria, a rare genetic light sensitivity disorder, and it has been approved in the EU since 2014. It is only available through specialist centers for that indication. The Melanotan I injections sold online for tanning are not the approved product and have no lawful route to consumers.", "source_ids": [ "scenesse-label", "langendonk-2015" ] }, { "q": "Does afamelanotide work?", "a": "For erythropoietic protoporphyria, yes, with a modest but meaningful effect. In the US phase 3 trial of 94 patients, pain-free sunlight exposure over 6 months rose from a median 40.8 hours on placebo to 69.4 hours on afamelanotide. In the EU trial of 74 patients over 9 months, it rose from 0.8 to 6.0 hours and phototoxic reactions roughly halved. Quality of life improved in both trials.", "source_ids": [ "langendonk-2015" ] }, { "q": "Can I use Melanotan I for tanning?", "a": "Not lawfully. Scenesse is approved only for erythropoietic protoporphyria and is dispensed through specialist centers. No regulator has approved any melanocortin agonist for cosmetic tanning, and injectable products sold online under the Melanotan I name are unapproved drugs of unknown purity. The label also requires twice yearly skin checks because the drug darkens moles and produces new ones.", "source_ids": [ "scenesse-label", "fda-compounding-qa" ] }, { "q": "What are the side effects of afamelanotide?", "a": "In trials adverse events were mostly mild: implant site reactions, nausea, headache, fatigue, nasopharyngitis, and skin darkening including darkening of existing moles and new freckles or naevi. Because of the pigment effects, the label recommends a full body skin examination twice a year. Serious adverse events in the trials were not attributed to the drug.", "source_ids": [ "langendonk-2015", "scenesse-label" ] }, { "q": "What is the Scenesse (afamelanotide) dose on the FDA label?", "a": "One 16 mg implant inserted under the skin above the hip bone every 2 months by a trained healthcare professional; it is not a self injection. Patients keep up sun and light protection during treatment. The label covers only adults with erythropoietic protoporphyria; there is no labeled dose for tanning.", "source_ids": [ "scenesse-label" ] }, { "q": "How much does Scenesse cost?", "a": "It is an orphan drug priced in the tens of thousands of USD per implant before insurance, with several implants per year. For approved patients, insurance coverage and manufacturer support programs determine the actual out of pocket cost. There is no cosmetic or cash pay market through licensed channels.", "source_ids": [ "scenesse-label" ] }, { "q": "Is Melanotan I banned by WADA?", "a": "No. Afamelanotide is an approved medicine and is not named in any section of the WADA Prohibited List. Athletes with erythropoietic protoporphyria can use it, though checking with their anti-doping organization is prudent; gray market Melanotan I products may contain other substances.", "source_ids": [ "wada-list" ] }, { "q": "Melanotan I vs Melanotan II: which is safer?", "a": "Melanotan I (afamelanotide) is selective for the skin MC1R receptor, has two randomized trials, an FDA approval, and a defined safety monitoring plan. Melanotan II activates several melanocortin receptors, causes nausea, erections, and appetite loss, was never approved, and was placed on the FDA Category 2 compounding list because of case reports of melanoma, priapism, and other serious events before its nomination was withdrawn in April 2026. Only afamelanotide has a lawful route, and only for its approved disease.", "source_ids": [ "langendonk-2015", "fda-cat2" ] } ], "studies": [ { "pmid": "26132941", "title": "Afamelanotide for erythropoietic protoporphyria", "year": 2015, "design": "Two multicenter randomized, double-blind, placebo-controlled trials of 16 mg implants every 60 days (US 180 days, EU 270 days)", "n": 168, "population": "Adults with erythropoietic protoporphyria (94 in the US trial, 74 in the EU trial)", "outcome": "Median pain-free direct sunlight exposure 69.4 versus 40.8 hours (US, p = 0.04) and 6.0 versus 0.8 hours (EU, p = 0.005); phototoxic reactions 77 versus 146 (EU); improved quality of life; mostly mild adverse events", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26132941/" }, { "pmid": "33683075", "title": "Afamelanotide: an orphan drug with potential for broad dermatologic applications", "year": 2021, "design": "Narrative review", "population": "Patients with erythropoietic protoporphyria and other photodermatoses in published studies", "outcome": "Summarizes the MC1R mechanism, the phase 3 evidence, the safety monitoring requirements, and investigational uses in vitiligo and other conditions", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33683075/" } ], "sources": [ { "id": "langendonk-2015", "type": "pubmed", "title": "Langendonk JG et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26132941/", "pmid": "26132941", "year": 2015 }, { "id": "wu-2021", "type": "pubmed", "title": "Wu J et al. Afamelanotide: an orphan drug with potential for broad dermatologic applications. J Drugs Dermatol 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33683075/", "pmid": "33683075", "year": 2021 }, { "id": "scenesse-label", "type": "fda", "title": "FDA prescribing information for Scenesse (afamelanotide) implant, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "melanotan-ii", "pt-141", "ghk-cu" ], "cluster": "sexual_health", "last_verified": "2026-09-23", "review_status": "draft", "version": 4, "seo": { "title": "Melanotan I (Scenesse): uses, side effects, legal status", "description": "Scenesse is afamelanotide, the approved form of melanotan I, an implant for erythropoietic protoporphyria. Label use and dose, side effects, and tanning risks.", "h1": "Melanotan I (afamelanotide, Scenesse)" } }, { "slug": "gonadorelin", "name": "Gonadorelin", "aliases": [ "GnRH", "Gonadotropin-releasing hormone", "LHRH", "Gonadorelin acetate", "Gonadorelin hydrochloride", "Factrel", "Lutrepulse" ], "class": "Synthetic decapeptide identical to native human gonadotropin-releasing hormone", "one_liner": "Native GnRH: proven when pumped in pulses for hypothalamic infertility, unstudied as the 2 to 3 times weekly TRT add-on clinics now sell.", "summary": "Gonadorelin is synthetic gonadotropin-releasing hormone, the hypothalamic decapeptide that tells the pituitary to release LH and FSH. Delivered in pulses every 60 to 120 minutes by a portable pump it restores ovulation in most women with hypothalamic amenorrhea and induces sperm production in men with hypogonadotropic hypogonadism, which is how the discontinued approved products (Factrel for diagnosis, Lutrepulse for ovulation induction) were used. The compounded gonadorelin that telehealth clinics prescribe as a few subcutaneous injections per week alongside testosterone, replacing hCG after hCG became a biologic in 2020, has no trial evidence and is pharmacologically doubtful because gonadorelin's half-life is only a few minutes.", "mechanism": "Gonadorelin binds GnRH receptors on pituitary gonadotroph cells and triggers release of LH and FSH, which stimulate testicular testosterone production and spermatogenesis or ovarian follicle development. The pituitary responds only to pulsatile GnRH: continuous or high dose exposure downregulates the receptor and suppresses gonadotropins, which is how GnRH agonists such as leuprolide work. Its plasma half-life is about 2 to 4 minutes, so a single subcutaneous injection produces a brief LH pulse rather than sustained stimulation.", "evidence_grade": "human_observational", "evidence_summary": "Pulsatile GnRH by pump has decades of clinical evidence, mostly observational. A 2018 systematic review and meta-analysis of 35 studies (3 randomized, 32 observational; 1,002 women) with hypothalamic amenorrhea found high ovulation rates, comparable results for subcutaneous and intravenous delivery, and a low incidence of mild ovarian hyperstimulation. In men with hypogonadotropic hypogonadism, a 42 patient series found pulsatile GnRH and hCG plus hMG equally effective, inducing sperm in 54 of 57 treatment courses and pregnancy in 26 of 36. There is no published study of intermittent subcutaneous gonadorelin injections 2 to 3 times per week as an adjunct to testosterone therapy.", "human_evidence": "Tranoulis 2018: systematic review and meta-analysis of pulsatile GnRH in 1,002 women with idiopathic or functional hypothalamic amenorrhea across 35 studies; high ovulation rates, trend toward high pregnancy and live birth rates per ovulatory cycle, low and mild ovarian hyperstimulation, slightly elevated multiple gestation versus the general population. Quaas 2022: 25 year single center cohort of pulsatile GnRH in functional hypothalamic amenorrhea reporting monofollicular ovulation and high cumulative live birth rates. Büchter 1998: 42 men with hypogonadotropic hypogonadism treated with pulsatile GnRH or hCG/hMG; testicular volume doubled within 5 to 12 months, sperm appeared in 54 of 57 courses, pregnancies in 26 of 36, with no significant difference between GnRH and gonadotropins. Dwyer 2024: review of fertility induction in congenital hypogonadotropic hypogonadism summarizing pulsatile GnRH and gonadotropin regimens.", "animal_evidence": "GnRH was isolated and sequenced from porcine and ovine hypothalami in 1971; primate studies by Knobil's group established that pulsatile but not continuous GnRH sustains gonadotropin secretion, the principle that underlies all pump protocols. Veterinary gonadorelin products are approved for cattle reproduction.", "conditions": [], "literature_dosing": "Pulsatile pump protocols in the literature and the former Lutrepulse label: 5 mcg gonadorelin acetate intravenously every 90 minutes (range 1 to 20 mcg per pulse) for ovulation induction, with subcutaneous pulses of similar size every 60 to 120 minutes used in many series; men with hypogonadotropic hypogonadism received subcutaneous pulses every 2 hours for months. Diagnostic use (former Factrel label): a single 100 mcg subcutaneous or intravenous dose to test pituitary LH response. No literature dosing exists for intermittent injections 2 to 3 times per week.", "routes": [ "Subcutaneous or intravenous pulsatile infusion by portable pump (evidence based use)", "Single subcutaneous or intravenous injection for pituitary function testing (former diagnostic use)", "Intermittent subcutaneous injections 2 to 3 times weekly (compounded TRT adjunct, no studies)" ], "side_effects": [ "Injection or infusion site reactions, including inflammation and, with intravenous pumps, rare thrombophlebitis", "Headache, nausea, abdominal discomfort, flushing, lightheadedness reported with diagnostic doses", "Ovarian hyperstimulation syndrome (uncommon and mild with pulsatile therapy) and multiple pregnancy", "Hypersensitivity reactions including anaphylaxis (rare)", "Antibody formation against gonadorelin reported with prolonged use", "Paradoxical suppression of LH and FSH if given continuously or at high frequency" ], "interactions": [ "Androgens, estrogens, progestins, and glucocorticoids blunt the pituitary response and confound diagnostic testing", "Dopamine antagonists, spironolactone, levodopa, and oral contraceptives can alter gonadotropin response to diagnostic doses", "GnRH agonists and antagonists (leuprolide, ganirelix, cetrorelix) block or override its effect", "Testosterone therapy suppresses the axis gonadorelin is meant to stimulate; the combination has not been studied" ], "contraindications": [ "Hypersensitivity to gonadorelin or components", "Pregnancy (former Lutrepulse label: discontinue once pregnancy is confirmed)", "Conditions that could be worsened by ovarian stimulation, such as ovarian cysts or undiagnosed vaginal bleeding", "Hormone dependent tumors (theoretical, via sex steroid stimulation)", "Male athletes subject to WADA testing (prohibited under S2)" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "Gonadorelin was the active ingredient of two FDA approved human products, Factrel (gonadorelin hydrochloride, a diagnostic for pituitary function) and Lutrepulse (gonadorelin acetate for pump delivered ovulation induction), both of which have been discontinued in the United States for commercial rather than safety reasons. Because it is a component of FDA approved drugs, 503A pharmacies can compound it under a prescription, which is why it is widely available as a compounded testosterone therapy adjunct. As a 10 amino acid peptide it was not affected by the March 2020 transition of hCG and other large proteins to biologic status, so it filled the gap when compounded hCG became unavailable. It is not on the FDA Category 2 list. The currently marketed FDA approved gonadorelin products are veterinary.", "typical_cost": "Compounded gonadorelin is usually priced per vial: 50 USD per vial as an add-on in a telehealth testosterone program whose fee is separate. Pulsatile pump therapy for infertility is delivered through reproductive endocrinology clinics, where the drug is a small part of the total cost of treatment. Prices checked 2026-09-22 on published provider and pharmacy price pages.", "access_path": [ "Prescription from a reproductive endocrinologist with a portable infusion pump for ovulation or spermatogenesis induction (compounded drug, since the approved products are discontinued).", "Prescription filled by a 503A compounding pharmacy as subcutaneous vials, usually through testosterone telehealth clinics.", "Not available as an FDA approved human product at present." ], "faqs": [ { "q": "Is gonadorelin legal in the United States?", "a": "Yes, by prescription. Gonadorelin was the active ingredient of the FDA approved human products Factrel and Lutrepulse, which were discontinued for commercial reasons, and that approval history lets 503A pharmacies compound it under a prescription. It is not on the FDA Category 2 list. Testosterone clinics prescribe it widely, although the way they use it has not been studied.", "source_ids": [ "drugs-at-fda", "fda-compounding-qa", "fda-cat2" ] }, { "q": "Does gonadorelin work as an hCG replacement on TRT?", "a": "Nobody has tested it. Clinics switched from hCG to gonadorelin after hCG became a biologic in 2020 and could no longer be compounded. hCG has at least retrospective data showing it preserves sperm production during testosterone therapy, but gonadorelin's half-life is a few minutes and it only stimulates the pituitary when delivered in pulses every 1 to 2 hours; two or three injections a week produce brief LH blips at best. No study has measured testicular volume, sperm counts, or testosterone recovery with that regimen.", "source_ids": [ "buchter-1998", "hsieh-2013", "fda-compounding-qa" ] }, { "q": "Does gonadorelin work for fertility?", "a": "When delivered in pulses by a pump, yes. A meta-analysis of 1,002 women with hypothalamic amenorrhea found high ovulation rates, mostly single pregnancies, and little ovarian hyperstimulation. In 42 men with hypogonadotropic hypogonadism, pulsatile GnRH or hCG plus hMG induced sperm production in 54 of 57 treatment courses and pregnancies in 26 of 36, with no difference between the two approaches. This requires a pump worn continuously for months, not weekly injections.", "source_ids": [ "tranoulis-2018", "buchter-1998" ] }, { "q": "What are the side effects of gonadorelin?", "a": "Diagnostic doses caused headache, nausea, flushing, abdominal discomfort, and injection site reactions. Pump therapy adds infusion site inflammation and, with intravenous pumps, occasional thrombophlebitis; ovarian hyperstimulation is uncommon and mild, and multiple pregnancy is slightly more likely than in the general population. Rare hypersensitivity and antibody formation have been reported. Giving it continuously or too often suppresses rather than stimulates the axis.", "source_ids": [ "tranoulis-2018", "drugs-at-fda" ] }, { "q": "How is gonadorelin taken and what dose was studied?", "a": "The evidence based regimen is a portable pump delivering about 5 mcg (range 1 to 20 mcg) intravenously every 90 minutes, or similar subcutaneous pulses every 60 to 120 minutes, for as long as it takes to ovulate or produce sperm. The diagnostic test was a single 100 mcg injection. The compounded 2 to 3 times weekly subcutaneous schedule sold by clinics has no literature dose.", "source_ids": [ "tranoulis-2018", "dwyer-2024" ] }, { "q": "How much does gonadorelin cost?", "a": "Compounded gonadorelin is usually sold per vial: 50 USD per vial as an add-on in a telehealth testosterone program, whose program fee is separate. Pump therapy for infertility is arranged through reproductive endocrinology clinics and the drug is a minor part of the overall cost. Prices checked 2026-09-22.", "source_ids": [ "price-telehealth-gonadorelin", "drugs-at-fda" ] }, { "q": "Is gonadorelin banned by WADA?", "a": "Yes, for male athletes. The WADA Prohibited List names gonadorelin explicitly in section S2 as a releasing factor for chorionic gonadotropin and LH, prohibited in males at all times. It is not prohibited in females. A therapeutic use exemption would be needed for any legitimate medical use by a male athlete.", "source_ids": [ "wada-list" ] }, { "q": "Gonadorelin vs hCG: which is better?", "a": "For inducing sperm production in hypogonadotropic men they performed equally in a 42 patient series, but gonadorelin needs a pump and hCG is injected 2 to 3 times a week, which is why hCG was the practical choice for decades. hCG has retrospective evidence for preserving sperm during testosterone therapy; gonadorelin has none. Since 2020 hCG is a biologic that cannot be compounded, so brand hCG is the only lawful hCG, while gonadorelin can be compounded. Both are prohibited for male athletes.", "source_ids": [ "buchter-1998", "hsieh-2013", "fda-compounding-qa" ] } ], "studies": [ { "pmid": "29605411", "title": "Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis", "year": 2018, "design": "Systematic review and meta-analysis of 35 studies (3 randomized, 32 observational)", "n": 1002, "population": "Women with idiopathic or functional hypothalamic amenorrhea treated with pulsatile GnRH", "outcome": "High ovulation rates, trend toward high pregnancy and live birth rates per ovulatory cycle, comparable subcutaneous and intravenous results, low and mild ovarian hyperstimulation", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/29605411/" }, { "pmid": "36378460", "title": "Use of pulsatile gonadotropin-releasing hormone (GnRH) in patients with functional hypothalamic amenorrhea (FHA) results in monofollicular ovulation and high cumulative live birth rates: a 25-year cohort", "year": 2022, "design": "Single center retrospective cohort over 25 years", "population": "Women with functional hypothalamic amenorrhea treated with pulsatile GnRH", "outcome": "Predominantly monofollicular ovulation and high cumulative live birth rates", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/36378460/" }, { "pmid": "9758439", "title": "Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases", "year": 1998, "design": "Single center case series", "n": 42, "population": "Men with idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, or hypopituitarism", "outcome": "Testicular volume doubled within 5 to 12 months; sperm induced in 54 of 57 courses; pregnancy in 26 of 36 courses; no significant difference between pulsatile GnRH and hCG/hMG", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9758439/" }, { "pmid": "39190467", "title": "Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism", "year": 2024, "design": "Narrative review", "population": "Men with congenital hypogonadotropic hypogonadism", "outcome": "Summarizes pulsatile GnRH and gonadotropin regimens, predictors of response, and the need for pulsatile delivery", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/39190467/" } ], "sources": [ { "id": "tranoulis-2018", "type": "pubmed", "title": "Tranoulis A et al. Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis. Fertil Steril 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29605411/", "pmid": "29605411", "year": 2018 }, { "id": "quaas-2022", "type": "pubmed", "title": "Quaas P et al. Use of pulsatile GnRH in patients with functional hypothalamic amenorrhea results in monofollicular ovulation and high cumulative live birth rates: a 25-year cohort. J Assist Reprod Genet 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36378460/", "pmid": "36378460", "year": 2022 }, { "id": "buchter-1998", "type": "pubmed", "title": "Buchter D et al. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9758439/", "pmid": "9758439", "year": 1998 }, { "id": "dwyer-2024", "type": "pubmed", "title": "Dwyer AA et al. Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism. Ann N Y Acad Sci 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39190467/", "pmid": "39190467", "year": 2024 }, { "id": "hsieh-2013", "type": "pubmed", "title": "Hsieh TC et al. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23260550/", "pmid": "23260550", "year": 2013 }, { "id": "drugs-at-fda", "type": "fda", "title": "Drugs@FDA database (search gonadorelin for the discontinued Factrel and Lutrepulse approvals)", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm", "year": 2026 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers (including that biological products cannot be compounded under 503A or 503B)", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "fda-cat2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2 list and withdrawn nominations, current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-telehealth-gonadorelin", "type": "other", "title": "Licensed telehealth provider price page for compounded gonadorelin, accessed 2026-09-22", "url": "https://fyrebody.com/products/gonadorelin-hcl" } ], "related": [ "hcg", "kisspeptin-10", "leuprolide", "triptorelin" ], "cluster": "sexual_health", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Gonadorelin: uses, side effects, and legal status", "description": "Gonadorelin is synthetic GnRH. Its human FDA-approved products were discontinued, so its legal status, TRT use, evidence, side effects, and cost are explained.", "h1": "Gonadorelin (synthetic GnRH)" } }, { "slug": "hcg", "name": "HCG (human chorionic gonadotropin)", "aliases": [ "hCG", "Chorionic gonadotropin", "Pregnyl", "Novarel", "Ovidrel (choriogonadotropin alfa)", "Chorionic gonadotropin for injection" ], "class": "Glycoprotein hormone of the placenta (heterodimer of alpha and beta subunits, about 237 amino acids) that acts on the LH receptor; regulated as a biologic since 2020", "one_liner": "FDA approved hormone for infertility and male hypogonadism; useless for weight loss and no longer compoundable since it became a biologic in 2020.", "summary": "Human chorionic gonadotropin is a placental glycoprotein hormone that mimics LH, approved by FDA for ovulation induction, cryptorchidism, and hypogonadotropic hypogonadism in men (Pregnyl, Novarel, and the recombinant Ovidrel). Retrospective data show low dose hCG preserves sperm production in men on testosterone therapy, and it reliably induces spermatogenesis in hypogonadotropic men, but a criteria-based meta-analysis found no evidence it helps weight loss and FDA states hCG diet products are illegal. On March 23, 2020 hCG transitioned to regulation as a biologic, which ended compounded hCG because biologics cannot be compounded under 503A or 503B.", "mechanism": "hCG binds the LH/hCG receptor on testicular Leydig cells and ovarian theca and granulosa cells. In men it drives intratesticular testosterone production, which sustains spermatogenesis even when pituitary LH is suppressed by exogenous testosterone. In women a single large dose mimics the LH surge and triggers final oocyte maturation and ovulation. Its long half-life (about 24 to 36 hours) allows dosing 2 to 3 times per week rather than the pulsatile delivery GnRH requires. It has no established mechanism affecting fat metabolism.", "evidence_grade": "human_rct", "evidence_summary": "hCG is standard of care for triggering ovulation in assisted reproduction and for inducing puberty and fertility in men with hypogonadotropic hypogonadism, supported by decades of trials and label evidence. In a 42 patient series, hCG plus hMG induced sperm in most hypogonadotropic men with results equal to pulsatile GnRH. A retrospective study of 26 men on testosterone therapy given 500 IU hCG every other day found no decline in semen parameters and no azoospermia over 6 months. For obesity, a criteria-based meta-analysis of 24 trials concluded there is no scientific evidence that hCG causes weight loss, fat redistribution, reduced hunger, or improved well-being. For testosterone recovery after anabolic steroid use, evidence is limited to case series and expert reviews.", "human_evidence": "Hsieh 2013: retrospective review of 26 hypogonadal men on testosterone (injection or gel) with concomitant intramuscular hCG 500 IU every other day; serum testosterone rose from 207 to 1,056 ng/dL, semen parameters were unchanged over more than a year of follow up, no patient became azoospermic, and 9 of 26 contributed to a pregnancy. Büchter 1998: hCG/hMG or pulsatile GnRH in 42 hypogonadotropic men induced sperm in 54 of 57 courses and pregnancy in 26 of 36. Amory 2008: in gonadotropin suppressed normal men, graded hCG doses maintained intratesticular testosterone in a dose dependent way. Lijesen 1995: meta-analysis of 8 controlled and 16 uncontrolled trials of hCG for obesity; of 12 higher quality studies only one favored hCG, and the authors concluded there is no evidence of benefit for weight, fat distribution, hunger, or well-being.", "animal_evidence": "hCG stimulates testosterone secretion and spermatogenesis in rodents and primates through the LH receptor and induces ovulation in many species. Animal work established the LH receptor pharmacology and the absence of any lipolytic effect.", "conditions": [], "literature_dosing": "FDA labels (Pregnyl and Novarel, DailyMed; intramuscular use only; the labels list regimens advocated by various authorities): prepubertal cryptorchidism not due to anatomic obstruction, for example 4,000 USP units three times weekly for 3 weeks or 5,000 units every second day for 4 injections; selected cases of hypogonadotropic hypogonadism in males, 500 to 1,000 units three times a week for 3 weeks followed by the same dose twice a week for 3 weeks, or 4,000 units three times weekly for 6 to 9 months followed by 2,000 units three times weekly for 3 more months; induction of ovulation, 5,000 to 10,000 units one day after the last dose of menotropins. Ovidrel (recombinant, subcutaneous): 250 mcg one day after the last dose of the follicle stimulating agent. Both urinary labels state that hCG has not been demonstrated to be effective adjunctive therapy for obesity.", "routes": [ "Intramuscular injection (Pregnyl, Novarel labels)", "Subcutaneous injection (Ovidrel prefilled syringe; also common off-label practice with urinary hCG)", "Oral drops, pellets, and sprays sold for the hCG diet contain no meaningful hCG and are illegal per FDA" ], "side_effects": [ "Headache, irritability, restlessness, depression, fatigue", "Edema and fluid retention", "Gynecomastia and breast tenderness (via increased estradiol)", "Precocious puberty when used in boys for cryptorchidism", "Ovarian hyperstimulation syndrome and multiple pregnancy in women", "Arterial and venous thromboembolism (rare)", "Injection site pain and hypersensitivity reactions", "Acne and rising estradiol in men on higher doses" ], "interactions": [ "Aromatase inhibitors and SERMs are sometimes co-prescribed to manage estradiol rise; combined use has not been studied in trials", "Testosterone therapy: hCG is used concurrently to maintain intratesticular testosterone (retrospective data only)", "Can cause false positive pregnancy tests and interfere with hCG based tumor marker assays for up to 10 days" ], "contraindications": [ "Precocious puberty", "Prostate cancer or other androgen dependent neoplasm", "Prior hypersensitivity to hCG", "Women: primary ovarian failure, uncontrolled thyroid or adrenal dysfunction, sex hormone dependent tumors, abnormal uterine bleeding of undetermined origin, ovarian cysts not due to polycystic ovary syndrome, pregnancy", "Male athletes subject to WADA testing (prohibited under S2)" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "hCG is FDA approved as Pregnyl and Novarel (urinary derived chorionic gonadotropin) and Ovidrel (recombinant choriogonadotropin alfa). On March 23, 2020 these products transitioned from drug approvals to biologics license applications under the Biologics Price Competition and Innovation Act. FDA states that biological products are not eligible for the 503A or 503B compounding exemptions, so compounded hCG, which had been common in testosterone and weight loss clinics, became unlawful at that point. FDA has separately stated that over the counter hCG diet products are illegal and that hCG is not approved for weight loss. It is not on the FDA Category 2 list because it is an approved biologic rather than a bulk drug substance nomination.", "typical_cost": "Brand hCG (Pregnyl, Novarel) costs roughly 100 to 300 USD per 10,000 unit vial at retail pharmacies, which at 500 IU three times a week lasts about 6 to 7 weeks; Ovidrel prefilled syringes run roughly 150 to 250 USD each. Compounded hCG is no longer lawfully available. Prices verified on the last verified date.", "access_path": [ "Prescription from a urologist, endocrinologist, or reproductive specialist filled at a retail or specialty pharmacy as Pregnyl, Novarel, or Ovidrel.", "Telehealth testosterone clinics can prescribe brand hCG but cannot lawfully supply compounded hCG.", "hCG diet products sold without a prescription are illegal and do not contain effective hCG." ], "faqs": [ { "q": "Is hCG legal and FDA approved, and what is it used for?", "a": "Yes, by prescription. The Pregnyl and Novarel labels cover prepubertal cryptorchidism not due to anatomic obstruction, selected cases of hypogonadotropic hypogonadism in males, and induction of ovulation in anovulatory infertile women after pretreatment with menotropins. Ovidrel covers final follicular maturation in assisted reproduction and ovulation induction. The urinary labels state that hCG has not been shown to be effective for obesity. Since March 2020 hCG is regulated as a biologic, and FDA states biologics cannot be compounded, so compounded hCG from 503A pharmacies is no longer lawful. Over the counter hCG diet drops and pellets are illegal according to FDA.", "source_ids": [ "pregnyl-label", "novarel-label", "ovidrel-label", "fda-compounding-qa", "fda-hcg-diet" ] }, { "q": "Does hCG work for weight loss?", "a": "No. A criteria-based meta-analysis of 24 trials found that of the 12 better quality controlled studies, only one favored hCG, and concluded there is no scientific evidence it causes weight loss, fat redistribution, reduced hunger, or a sense of well-being. The prescription label itself says hCG is not effective adjunctive therapy for obesity, and FDA calls hCG diet products illegal. Any weight lost on the hCG diet comes from its 500 calorie per day restriction.", "source_ids": [ "lijesen-1995", "fda-hcg-diet", "pregnyl-label" ] }, { "q": "Does hCG preserve fertility on testosterone therapy?", "a": "The best available data say yes, but they are retrospective. In 26 men on testosterone who also received 500 IU hCG every other day, semen parameters did not decline over more than a year, none became azoospermic, and 9 contributed to a pregnancy. A dose ranging study in gonadotropin suppressed men showed hCG maintains intratesticular testosterone. No randomized trial has confirmed the fertility outcome.", "source_ids": [ "hsieh-2013", "amory-2008" ] }, { "q": "What are the side effects of hCG?", "a": "In men: headache, irritability, fatigue, fluid retention, gynecomastia and breast tenderness from rising estradiol, acne, and injection site pain; in boys it can trigger early puberty. In women: ovarian hyperstimulation syndrome and multiple pregnancy. Rare thromboembolic events and allergic reactions are reported. It can cause false positive pregnancy tests for several days.", "source_ids": [ "pregnyl-label", "novarel-label" ] }, { "q": "What is the hCG dose on the FDA label?", "a": "Pregnyl and Novarel are labeled for intramuscular injection. For hypogonadotropic hypogonadism in males the listed regimens include 500 to 1,000 units three times a week for 3 weeks then twice a week for 3 weeks, or 4,000 units three times a week for 6 to 9 months then 2,000 units three times a week for 3 months. Ovulation induction uses a single 5,000 to 10,000 unit dose one day after the last menotropins dose; Ovidrel is 250 mcg under the skin. Use alongside testosterone therapy is off label.", "source_ids": [ "pregnyl-label", "novarel-label", "ovidrel-label" ] }, { "q": "How much does hCG cost?", "a": "Brand hCG costs roughly 100 to 300 USD per 10,000 unit vial, which lasts about 6 to 7 weeks at 500 IU three times weekly, and Ovidrel syringes are roughly 150 to 250 USD each. Compounded hCG, which used to be cheaper, is no longer lawfully available. Prices verified on the last verified date.", "source_ids": [ "pregnyl-label", "fda-compounding-qa" ] }, { "q": "Is hCG banned by WADA?", "a": "Yes, for male athletes. Chorionic gonadotropin is named in section S2 of the WADA Prohibited List, prohibited in males at all times because it raises testosterone. It is not prohibited in females. Male athletes with a legitimate medical need must obtain a therapeutic use exemption.", "source_ids": [ "wada-list" ] }, { "q": "hCG vs gonadorelin: which should I use with TRT?", "a": "hCG has the evidence. It acts directly on the testes with a long half-life, so 2 to 3 injections a week maintain intratesticular testosterone, and retrospective data show preserved sperm production during testosterone therapy. Gonadorelin acts on the pituitary, lasts minutes, and only works when pumped in pulses; the weekly injection schedule clinics sell has never been studied. The practical problem is that only brand hCG is lawful now, while gonadorelin can be compounded cheaply.", "source_ids": [ "hsieh-2013", "buchter-1998", "fda-compounding-qa" ] } ], "studies": [ { "pmid": "23260550", "title": "Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy", "year": 2013, "design": "Retrospective single center review, hCG 500 IU intramuscularly every other day with testosterone", "n": 26, "population": "Hypogonadal men (mean age 35.9) on testosterone injection or gel", "outcome": "Testosterone rose from 207 to 1,056 ng/dL; semen volume, density, motility, and forward progression unchanged over more than 1 year; no azoospermia; 9 of 26 contributed to pregnancy", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/23260550/" }, { "pmid": "17462643", "title": "Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin-suppressed normal men receiving various dosages of human chorionic gonadotropin", "year": 2008, "design": "Prospective dose ranging study with testicular aspiration", "population": "Healthy men with gonadotropins suppressed by exogenous testosterone", "outcome": "hCG maintained intratesticular testosterone in a dose dependent manner; serum 17-hydroxyprogesterone tracked intratesticular testosterone", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/17462643/" }, { "pmid": "9758439", "title": "Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases", "year": 1998, "design": "Single center case series", "n": 42, "population": "Men with hypogonadotropic hypogonadism or hypopituitarism", "outcome": "Sperm induced in 54 of 57 treatment courses and pregnancy in 26 of 36 courses; hCG/hMG and pulsatile GnRH performed equally", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9758439/" }, { "pmid": "8527285", "title": "The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis", "year": 1995, "design": "Criteria-based meta-analysis of 8 controlled and 16 uncontrolled trials", "population": "Adults with obesity treated with hCG plus very low calorie diet", "outcome": "Of 12 higher quality (all controlled) studies only one favored hCG; no evidence hCG produces weight loss, fat redistribution, reduced hunger, or improved well-being", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/8527285/" } ], "sources": [ { "id": "hsieh-2013", "type": "pubmed", "title": "Hsieh TC et al. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23260550/", "pmid": "23260550", "year": 2013 }, { "id": "amory-2008", "type": "pubmed", "title": "Amory JK et al. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin-suppressed normal men receiving various dosages of human chorionic gonadotropin. Fertil Steril 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/17462643/", "pmid": "17462643", "year": 2008 }, { "id": "buchter-1998", "type": "pubmed", "title": "Buchter D et al. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9758439/", "pmid": "9758439", "year": 1998 }, { "id": "lijesen-1995", "type": "pubmed", "title": "Lijesen GK et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Br J Clin Pharmacol 1995", "url": "https://pubmed.ncbi.nlm.nih.gov/8527285/", "pmid": "8527285", "year": 1995 }, { "id": "pregnyl-label", "type": "fda", "title": "FDA prescribing information for Pregnyl (chorionic gonadotropin) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e94155f-19be-4944-b197-be4edbb4faf9", "year": 2025 }, { "id": "novarel-label", "type": "fda", "title": "FDA prescribing information for Novarel (chorionic gonadotropin) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac6918ff-9dc3-40d9-8619-54b26e4bdfc8", "year": 2025 }, { "id": "fda-hcg-diet", "type": "fda", "title": "FDA consumer update: Avoid dangerous HCG diet products (hCG is not approved for weight loss; over the counter hCG products are illegal)", "url": "https://www.fda.gov/consumers/consumer-updates/avoid-dangerous-hcg-diet-products", "year": 2025 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers (biological products are not eligible for the 503A or 503B compounding exemptions)", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "ovidrel-label", "type": "fda", "title": "FDA prescribing information for Ovidrel (choriogonadotropin alfa injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a683e58a-63ea-44b8-a326-1a99a537bcf2", "year": 2023 } ], "related": [ "gonadorelin", "kisspeptin-10", "leuprolide", "ganirelix" ], "cluster": "sexual_health", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "hCG (Pregnyl, Novarel): uses, side effects, and dosing", "description": "Pregnyl, Novarel, and Ovidrel are hCG. FDA label uses (fertility, cryptorchidism, male hypogonadism), label doses, side effects, and why hCG diets fail.", "h1": "hCG (Pregnyl, Novarel, Ovidrel)" } }, { "slug": "tesamorelin", "name": "Tesamorelin", "aliases": [ "Egrifta", "Egrifta SV", "Egrifta WR", "TH9507", "Tesamorelin acetate", "GHRH(1-44) analog" ], "class": "Synthetic 44 amino acid analog of human growth hormone releasing hormone with an N-terminal trans-3-hexenoic acid modification that resists enzymatic degradation", "one_liner": "FDA approved lab-made growth hormone releasing hormone (Egrifta, 2010) that cuts deep belly fat about 15% in HIV lipodystrophy and cut liver fat in a trial.", "summary": "Tesamorelin is a stabilized growth hormone releasing hormone analog, a lab-made version of the brain signal that tells the pituitary to release growth hormone, approved by FDA in 2010 as Egrifta for reducing excess abdominal fat in adults with HIV who have lipodystrophy (an abnormal shift of body fat linked to HIV and its treatment); the current formulations are Egrifta WR and Egrifta SV. In pooled phase 3 trials of 806 patients, 2 mg daily for 26 weeks reduced visceral adipose tissue (deep belly fat around the organs) by 15.4% relative to placebo and lowered triglycerides (blood fats) without meaningful changes in glucose, and a later 61 patient randomized trial in HIV associated fatty liver cut liver fat by 37% relative to baseline. Outside HIV, one 60 person trial in abdominal obesity with reduced growth hormone secretion found a similar visceral fat drop, but use for fat loss or anti-aging in people without HIV is off-label (outside the approved use), and tesamorelin is prohibited in sport under WADA section S2.", "mechanism": "Tesamorelin binds pituitary GHRH receptors and stimulates pulsatile release of endogenous growth hormone, which raises IGF-1. Growth hormone increases lipolysis, particularly of visceral fat, and the physiological feedback loops remain intact, which is why tesamorelin causes less glucose disturbance than direct growth hormone injection. The hexenoyl modification protects the peptide from dipeptidyl peptidase cleavage, extending its action compared with native GHRH or sermorelin.", "evidence_grade": "human_rct", "evidence_summary": "Two multicenter, double-blind, placebo-controlled phase 3 trials with 806 HIV patients on antiretroviral therapy with excess abdominal fat (pooled analysis, Falutz 2010): at 26 weeks visceral adipose tissue fell 24 cm2 versus a 2 cm2 rise on placebo (treatment effect minus 15.4%), triglycerides fell 37 mg/dL versus a 6 mg/dL rise, IGF-1 rose 108 ng/mL, and glucose parameters did not differ meaningfully; visceral fat returned toward baseline after discontinuation. A 12 month NIH funded randomized trial in 61 people with HIV and nonalcoholic fatty liver disease (Stanley 2019) found an absolute reduction in hepatic fat fraction of 4.1 percentage points (37% relative reduction) and resolution of steatosis in 35% versus 4% on placebo, with more injection site complaints but no glucose difference. Outside HIV, a 12 month randomized trial in 60 abdominally obese adults with reduced GH secretion (Makimura 2012) found a visceral fat treatment effect of minus 35 cm2 with lower triglycerides and C-reactive protein and no change in glucose. A 2026 meta-analysis of five randomized trials in HIV found lower visceral, trunk, and liver fat and about 1.4 kg more lean body mass than placebo, with no significant change in subcutaneous fat or BMI.", "human_evidence": "Falutz 2010: pooled analysis of two phase 3 trials, 806 patients randomized 2:1 to tesamorelin 2 mg or placebo subcutaneously daily; VAT change minus 24 versus plus 2 cm2 at 26 weeks (p < 0.001), no change in abdominal subcutaneous fat, triglycerides minus 37 versus plus 6 mg/dL, improved patient rated belly appearance; in patients continued to 52 weeks VAT reduction was maintained at minus 17.5%, and those switched to placebo regained visceral fat. Stanley 2019: 61 patients with HIV and hepatic fat fraction of 5% or more randomized to tesamorelin 2 mg or placebo daily for 12 months; hepatic fat fraction fell by an absolute 4.1% (95% CI minus 7.6 to minus 0.7) and 35% versus 4% reached a hepatic fat fraction below 5%; fasting glucose and HbA1c did not differ. Stanley 2012: reductions in visceral fat with tesamorelin were associated with improved triglycerides and adiponectin. Makimura 2012: 60 abdominally obese adults without HIV and with reduced GH secretion randomized to tesamorelin 2 mg or placebo daily for 12 months; visceral fat minus 16 versus plus 19 cm2 (treatment effect minus 35 cm2), triglycerides and C-reactive protein improved, carotid intima media thickness fell, and fasting glucose, 2 hour glucose, and HbA1c did not change. Adrian 2019: secondary CT analysis of the phase 3 trials (193 tesamorelin responders, 148 placebo) found small increases in trunk muscle density and lean muscle area (about 0.6 to 1.1 cm2 per muscle group) at 26 weeks. Badran 2026: meta-analysis of five RCTs in HIV, lean body mass plus 1.42 kg and hepatic fat minus 4.28 percentage points versus placebo.", "animal_evidence": "Preclinical studies in rodents and dogs characterized tesamorelin's GHRH receptor agonism, growth hormone release, and pharmacokinetics; carcinogenicity studies in rodents informed labeling. Animal data are secondary to the human trials for this approved drug.", "conditions": [ "growth-hormone-deficiency", "hiv-lipodystrophy", "fatty-liver-disease", "fat-loss" ], "literature_dosing": "FDA label dosing (tesamorelin is FDA approved, so these are labeled doses in mg for the approved use). Egrifta WR (11.6 mg vial, label revised March 2025): 1.28 mg injected subcutaneously into the abdomen once daily. Egrifta SV (2 mg vial): 1.4 mg subcutaneously into the abdomen once daily. Original Egrifta (1 mg vials, approved 2010): 2 mg subcutaneously once daily, the dose used in the phase 3 trials and the 12 month fatty liver trial. The formulations differ in strength and preparation and the labels state they are not substitutable, so the dose depends on which product is prescribed. The label bases efficacy on 26 weeks of treatment and advises weighing whether to continue in people whose visceral fat has not fallen; in trials, visceral fat returned after stopping. There is no labeled dose for people without HIV lipodystrophy, and compounded tesamorelin has no FDA labeled dose.", "routes": [ "Subcutaneous injection into the abdomen once daily (Egrifta WR, Egrifta SV)", "No oral, sublingual, or nasal form is FDA approved or tested in a published trial" ], "side_effects": [ "Arthralgia (about 13%)", "Injection site reactions (redness, itching, pain, irritation, bruising) in 25% versus 14% on placebo over 26 weeks", "Peripheral edema, myalgia, pain in extremities", "Paresthesia and hypoesthesia", "Nausea, vomiting, rash", "Glucose intolerance: HbA1c reached 6.5% or higher in 5% versus 1% on placebo by week 26 (label advises checking glucose before and during treatment)", "Increased IGF-1 (label recommends monitoring; consider stopping if persistently elevated)", "Hypersensitivity reactions including rash, urticaria, and rare anaphylaxis", "Fluid retention (edema, carpal tunnel syndrome) typical of growth hormone axis stimulation" ], "interactions": [ "Glucocorticoids and other drugs metabolized by CYP450: growth hormone may alter cytochrome P450 activity; monitor drugs with narrow therapeutic windows", "Cortisone acetate and prednisone: growth hormone can inhibit 11 beta hydroxysteroid dehydrogenase type 1, potentially requiring glucocorticoid dose adjustment", "Insulin and antidiabetic drugs: tesamorelin can raise glucose; monitor and adjust" ], "contraindications": [ "Disruption of the hypothalamic pituitary axis from hypophysectomy, hypopituitarism, pituitary tumor or surgery, head irradiation, or head trauma", "Active malignancy (newly diagnosed or recurrent)", "Pregnancy (visceral fat increases normally in pregnancy and the drug may harm the fetus)", "Known hypersensitivity to tesamorelin or any ingredient in the product", "Athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Egrifta (tesamorelin for injection) on November 10, 2010, for reduction of excess abdominal fat in HIV infected adults with lipodystrophy; Egrifta SV, a 2 mg vial formulation, was approved in 2019, and Egrifta WR, an 11.6 mg vial formulation, in March 2025. Tesamorelin is a 44 amino acid protein, and on March 23, 2020 FDA deemed the Egrifta application (022505) to be a biologics license. FDA states that biological products are not eligible for the 503A or 503B compounding exemptions, so compounded tesamorelin sold by telehealth and anti-aging clinics has no lawful basis, and Egrifta WR by prescription is the only lawful product. A clinician may prescribe Egrifta WR off-label, but use for fat loss in people without HIV has only limited trial support.", "typical_cost": "Egrifta WR has no published list price; a retail cash listing put one 28 day kit at about 10,709 USD, and a manufacturer co-pay program helps eligible commercially insured patients with the approved HIV indication. Compounded tesamorelin has no lawful price, because tesamorelin is a biologic and biologics cannot be compounded. Prices checked 2026-09-22.", "access_path": [ "Prescription from an HIV specialist filled at a specialty pharmacy as Egrifta WR for the approved indication.", "Off-label prescription of Egrifta WR by a licensed clinician, usually paid in cash because coverage follows the HIV indication. Compounded tesamorelin is not a lawful option, because biologics cannot be compounded under 503A.", "Not available for athletic or cosmetic use through any lawful channel consistent with sport rules." ], "faqs": [ { "q": "What is tesamorelin and what does it do?", "a": "Tesamorelin is a lab-made version of growth hormone releasing hormone, the brain signal that tells the pituitary to release growth hormone. It raises the body's own growth hormone and IGF-1 (a growth factor that growth hormone raises), and in trials it reduced deep abdominal (visceral) fat without changing fat under the skin. FDA approved it in 2010 for one use: reducing excess abdominal fat in adults with HIV and lipodystrophy, an abnormal shift of body fat linked to HIV and its treatment. It is sold as Egrifta WR and Egrifta SV, and the label states it is not indicated for weight loss.", "source_ids": [ "dailymed-egrifta-wr", "falutz-2010" ] }, { "q": "Is tesamorelin legal and FDA approved?", "a": "Yes. Tesamorelin has been FDA approved since 2010, first as Egrifta and now as Egrifta WR and Egrifta SV, for reducing excess abdominal fat in adults with HIV lipodystrophy. It is prescription only. Because Egrifta became a biologic in 2020 and FDA states that biologics are not eligible for the 503A or 503B compounding exemptions, compounded tesamorelin has no lawful basis. A clinician may prescribe Egrifta WR off-label, but use for fat loss in people without HIV has little trial support.", "source_ids": [ "dailymed-egrifta-wr", "egrifta-label", "fda-compounding-qa", "fda-biologics-transition" ] }, { "q": "What is the tesamorelin dosage on the FDA label?", "a": "It depends on the formulation, and the labels state the formulations are not substitutable. Egrifta WR: 1.28 mg injected under the skin of the abdomen once daily. Egrifta SV: 1.4 mg once daily. The original Egrifta used in the phase 3 trials: 2 mg once daily. Treatment continues for as long as it is prescribed, because visceral fat returned after stopping in trials. There is no labeled dose for anyone without HIV lipodystrophy, and compounded tesamorelin has no FDA labeled dose.", "source_ids": [ "dailymed-egrifta-wr", "dailymed-egrifta-sv", "falutz-2010" ] }, { "q": "Does tesamorelin work for belly fat?", "a": "In HIV lipodystrophy, yes, modestly. In 806 patients, 2 mg daily for 26 weeks reduced visceral fat by 15.4% relative to placebo (about 24 cm2 on CT), lowered triglycerides, and improved how patients rated their belly, without changing subcutaneous fat or weight much. The fat came back after stopping. Outside HIV, one 12 month trial in 60 adults with abdominal obesity and reduced growth hormone secretion found visceral fat fell about 35 cm2 relative to placebo. It has not been tested as a general weight loss drug, and the label says it is not one.", "source_ids": [ "falutz-2010", "makimura-2012", "dailymed-egrifta-wr" ] }, { "q": "How long does tesamorelin take to work?", "a": "The approval trials measured results at 26 weeks, when visceral fat was 15.4% lower than on placebo, and the reduction held at 52 weeks in people who kept taking it. People switched to placebo regained visceral fat. The label advises weighing whether to continue in anyone whose visceral fat has not fallen. Trial results were measured by CT scans, which is why before and after photos are not a substitute for trial data.", "source_ids": [ "falutz-2010", "dailymed-egrifta-wr" ] }, { "q": "Does tesamorelin help build muscle?", "a": "It is not approved or tested for muscle growth. In a secondary analysis of the HIV trials, people whose visceral fat fell on tesamorelin (193, compared with 148 on placebo) had small gains in trunk muscle area, about 0.6 to 1.1 cm2 of lean area per muscle group on CT, and higher muscle density, a sign of less fat inside the muscle. A 2026 meta-analysis of five HIV trials found about 1.4 kg more lean body mass than placebo. No trial has tested it in healthy people or athletes, and it is prohibited in sport.", "source_ids": [ "adrian-2019", "badran-2026", "wada-list" ] }, { "q": "Is tesamorelin safe?", "a": "It has been through FDA review for its approved use, and the label lists real risks. It raises IGF-1, a growth factor, so it is contraindicated with active cancer and IGF-1 should be monitored. It can impair glucose tolerance: by week 26, 5% of treated patients versus 1% on placebo reached an HbA1c of 6.5% or higher. It can also cause fluid retention, joint pain, carpal tunnel symptoms, hypersensitivity reactions, and injection site reactions (25% versus 14% on placebo). Long-term cardiovascular safety has not been established. Compounded or research-labeled tesamorelin is not a lawful product and has not been tested the same way.", "source_ids": [ "dailymed-egrifta-wr", "falutz-2010", "fda-compounding-qa" ] }, { "q": "Can women take tesamorelin?", "a": "For the approved use, yes: the label covers adults with HIV and lipodystrophy, although about 85% of participants in the two phase 3 trials were men. It is contraindicated in pregnancy, because visceral fat normally rises in pregnancy and rat studies showed harm to offspring, and the label says to stop it if pregnancy occurs. The label also advises against breastfeeding while taking it. Use for fat loss in women without HIV is off-label.", "source_ids": [ "dailymed-egrifta-wr" ] }, { "q": "Is there a tesamorelin pill?", "a": "No. Every FDA approved tesamorelin product (Egrifta, Egrifta SV, and Egrifta WR) is a powder made into an injection given under the skin, and the trials behind the approval used daily injections. No oral, sublingual, or nasal tesamorelin has been approved or tested in a published trial, so products sold in those forms are unapproved and unstudied.", "source_ids": [ "dailymed-egrifta-wr", "dailymed-egrifta-sv", "falutz-2010" ] }, { "q": "Does tesamorelin help fatty liver?", "a": "In people with HIV, a 12 month NIH funded randomized trial of 61 patients found tesamorelin 2 mg daily reduced liver fat by an absolute 4.1 percentage points, a 37% relative reduction, and 35% of treated patients cleared steatosis versus 4% on placebo. Glucose did not worsen. It has not been tested for fatty liver in people without HIV and is not approved for that use.", "source_ids": [ "stanley-2019" ] }, { "q": "What are the side effects of tesamorelin?", "a": "Joint pain (about 13%), injection site redness, itching, and bruising (25% versus 14% on placebo), swelling of the hands and feet, muscle aches, tingling, and nausea are the common ones. Because it raises growth hormone and IGF-1 it can impair glucose tolerance, so the label advises checking blood sugar before and during treatment and monitoring IGF-1. It is contraindicated with active cancer, pituitary disease, and pregnancy.", "source_ids": [ "dailymed-egrifta-wr", "egrifta-label", "falutz-2010" ] }, { "q": "How much does tesamorelin cost?", "a": "Egrifta WR, which replaced Egrifta SV, has no published list price; a retail cash listing put one 28 day kit at about 10,709 USD, and a manufacturer co-pay program helps eligible commercially insured patients with the HIV indication. Compounded tesamorelin has no lawful price, because tesamorelin is a biologic and biologics cannot be compounded. Prices checked 2026-09-22.", "source_ids": [ "price-listing-egrifta-wr", "dailymed-egrifta-wr", "egrifta-label", "fda-biologics-transition" ] }, { "q": "Is tesamorelin banned by WADA?", "a": "Yes. The WADA Prohibited List names tesamorelin explicitly in section S2 among growth hormone releasing hormone analogues, prohibited at all times in and out of competition. An athlete with HIV lipodystrophy would need a therapeutic use exemption.", "source_ids": [ "wada-list" ] }, { "q": "Tesamorelin vs sermorelin: what is the difference?", "a": "Both are GHRH analogs, but tesamorelin is the full 44 amino acid sequence with a stabilizing modification and has large randomized trials plus a current FDA approval. Sermorelin is the 29 amino acid fragment, was approved as Geref for children with growth hormone deficiency, and was discontinued in 2008; its adult data are small and old. Tesamorelin is the better evidenced and much more expensive option; both are prohibited by WADA.", "source_ids": [ "falutz-2010", "wada-list" ] } ], "studies": [ { "pmid": "20554713", "title": "Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data", "year": 2010, "design": "Pooled analysis of two randomized, double-blind, placebo-controlled phase 3 trials, 26 weeks plus 26 week extension", "n": 806, "population": "Adults with HIV on antiretroviral therapy with excess abdominal fat", "outcome": "Visceral adipose tissue minus 24 versus plus 2 cm2 (treatment effect minus 15.4%), triglycerides minus 37 versus plus 6 mg/dL, IGF-1 plus 108 ng/mL, no meaningful glucose change; effect maintained at 52 weeks with continued treatment", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/20554713/" }, { "pmid": "31611038", "title": "Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial", "year": 2019, "design": "Randomized, double-blind, placebo-controlled trial, 12 months plus 6 month open-label phase", "n": 61, "population": "Adults with HIV and hepatic fat fraction of 5% or more", "outcome": "Hepatic fat fraction absolute change minus 4.1% (37% relative reduction); 35% versus 4% achieved hepatic fat below 5%; no difference in glucose or HbA1c", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31611038/" }, { "pmid": "22495074", "title": "Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin", "year": 2012, "design": "Secondary analysis of the phase 3 trials", "population": "HIV patients with excess abdominal fat treated with tesamorelin", "outcome": "Visceral fat reduction with tesamorelin was associated with improved triglycerides and adiponectin", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22495074/" }, { "pmid": "23015655", "title": "Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial", "year": 2012, "design": "Randomized, double-blind, placebo-controlled trial, 12 months", "n": 60, "population": "Abdominally obese adults without HIV with reduced growth hormone secretion", "outcome": "Visceral fat treatment effect minus 35 cm2; triglycerides, C-reactive protein, and carotid intima media thickness improved; no change in glucose or HbA1c", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23015655/" }, { "pmid": "31237318", "title": "The growth hormone releasing hormone analogue, tesamorelin, decreases muscle fat and increases muscle area in adults with HIV", "year": 2019, "design": "Secondary exploratory CT analysis of two randomized phase 3 trials, 26 weeks", "n": 341, "population": "Adults with HIV and abdominal obesity (tesamorelin visceral fat responders and placebo)", "outcome": "Greater increases in trunk muscle density and lean muscle area (about 0.6 to 1.1 cm2 per muscle group) than placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/31237318/" }, { "pmid": "41545261", "title": "Body composition, hepatic fat, metabolic, and safety outcomes of tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: a meta-analysis of randomized controlled trials", "year": 2026, "design": "Meta-analysis of five randomized controlled trials", "population": "Adults with HIV associated lipodystrophy", "outcome": "Visceral fat minus 27.7 cm2, hepatic fat minus 4.28 percentage points, lean body mass plus 1.42 kg versus placebo; no significant change in subcutaneous fat or BMI", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/41545261/" } ], "sources": [ { "id": "falutz-2010", "type": "pubmed", "title": "Falutz J et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab 2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20554713/", "pmid": "20554713", "year": 2010 }, { "id": "stanley-2019", "type": "pubmed", "title": "Stanley TL et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31611038/", "pmid": "31611038", "year": 2019 }, { "id": "stanley-2012", "type": "pubmed", "title": "Stanley TL et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22495074/", "pmid": "22495074", "year": 2012 }, { "id": "egrifta-label", "type": "fda", "title": "FDA prescribing information for Egrifta formulations (tesamorelin for injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=egrifta", "year": 2025 }, { "id": "fda-compounding-qa", "type": "fda", "title": "FDA: Compounding and the FDA, questions and answers (biological products are not eligible for the 503A or 503B compounding exemptions)", "url": "https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, including tesamorelin)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-listing-egrifta-wr", "type": "other", "title": "Published retail cash price listing for tesamorelin (Egrifta WR) kits, accessed 2026-09-22", "url": "https://www.drugs.com/price-guide/egrifta-wr" }, { "id": "dailymed-egrifta-wr", "type": "fda", "title": "FDA prescribing information for Egrifta WR (tesamorelin) for injection, 11.6 mg vial, via DailyMed (Indications, Dosage and Administration, Warnings and Precautions, Use in Specific Populations, and Clinical Studies sections)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75", "year": 2025 }, { "id": "dailymed-egrifta-sv", "type": "fda", "title": "FDA prescribing information for Egrifta SV (tesamorelin) for injection, 2 mg vial, via DailyMed (Dosage and Administration section)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224", "year": 2024 }, { "id": "makimura-2012", "type": "pubmed", "title": "Makimura H et al. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. J Clin Endocrinol Metab 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23015655/", "pmid": "23015655", "year": 2012 }, { "id": "adrian-2019", "type": "pubmed", "title": "Adrian S et al. The growth hormone releasing hormone analogue, tesamorelin, decreases muscle fat and increases muscle area in adults with HIV. J Frailty Aging 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31237318/", "pmid": "31237318", "year": 2019 }, { "id": "badran-2026", "type": "pubmed", "title": "Badran AS et al. Body composition, hepatic fat, metabolic, and safety outcomes of tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: a meta-analysis of randomized controlled trials. Obes Res Clin Pract 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41545261/", "pmid": "41545261", "year": 2026 }, { "id": "fda-biologics-transition", "type": "fda", "title": "FDA: List of approved NDAs for biological products that were deemed to be BLAs on March 23, 2020 (includes tesamorelin, Egrifta and Egrifta SV, application 022505)", "url": "https://www.fda.gov/media/119229/download", "year": 2020 } ], "related": [ "sermorelin", "cjc-1295", "ipamorelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 4, "seo": { "title": "Tesamorelin (Egrifta): evidence, side effects, dosing", "description": "Tesamorelin (Egrifta WR, Egrifta SV): FDA label dosage, side effects, safety, and what trials showed for belly fat, liver fat, and muscle.", "h1": "Tesamorelin (Egrifta)", "headings": { "safety": "Tesamorelin side effects" } } }, { "slug": "sermorelin", "name": "Sermorelin", "aliases": [ "Sermorelin acetate", "GHRH(1-29)-NH2", "GRF 1-29", "Geref", "Growth hormone releasing hormone 1-29" ], "class": "Synthetic 29 amino acid N-terminal fragment of human growth hormone releasing hormone (GHRH 1-29), the shortest fragment with full GHRH receptor activity", "one_liner": "Formerly FDA approved piece of growth hormone releasing hormone (Geref, withdrawn 2009 for business reasons); small trials show higher GH and IGF-1.", "summary": "Sermorelin is the first 29 amino acids of human growth hormone releasing hormone (GHRH), the brain hormone that tells the pituitary to release growth hormone. It raises growth hormone and IGF-1 (a growth factor that growth hormone raises) in humans, and it was FDA approved as Geref for diagnosing GH deficiency (1990) and treating GH deficiency of unknown cause in children (1997) before the sponsor withdrew both NDAs, its approved drug applications, in 2009 for reasons FDA later confirmed were not safety or effectiveness. In adults the best trial is a 19 person, 16 week study showing higher IGF-1, thicker skin, and a small gain in lean mass in men only; there is no current FDA approved product and compounded (pharmacy-made) sermorelin sold by telehealth clinics for anti-aging or fat loss rests on that limited evidence.", "mechanism": "Sermorelin binds the GHRH receptor on pituitary somatotrophs and stimulates synthesis and pulsatile release of growth hormone, which in turn raises hepatic IGF-1. Because it works upstream of the pituitary, the response is limited by somatostatin tone and by the pituitary's own capacity, so it cannot push GH to the levels seen with injected recombinant GH. Its plasma half life is minutes, which is why it is given by nightly or twice daily subcutaneous injection.", "evidence_grade": "human_rct", "evidence_summary": "Human data are real but small and mostly from the 1980s and 1990s. Dose response studies in healthy men established that intravenous, subcutaneous, and intranasal GHRH(1-29) release GH acutely. A 12 month open study in 18 short children raised height velocity from 4.8 to 7.2 cm per year. A single blind, placebo controlled, 5 month trial in 19 adults aged 55 to 71 raised nocturnal GH and IGF-1 and increased skin thickness in both sexes, with lean mass, insulin sensitivity, and well being gains in men only; sleep quality did not change. No trial has tested sermorelin for fat loss, athletic performance, or longevity in adults, and the pediatric approval rested on growth velocity, not long term outcomes.", "human_evidence": "Vance 1986: dose response in normal men showed GH release after intravenous, subcutaneous, and intranasal [Nle27]GHRH(1-29). Kirk 1994: 18 prepubertal children with idiopathic short stature given 20 ug/kg subcutaneously twice daily for 12 months; mean height velocity rose from 4.8 to 7.2 cm per year (p = 0.001) with catch down growth after stopping. Khorram 1997: 10 women and 9 men aged 55 to 71 self injected placebo nightly for 4 weeks then 10 ug/kg [Nle27]GHRH(1-29) nightly for 16 weeks; 12 hour nocturnal GH and IGF-1 rose significantly, skin thickness increased in both sexes, lean body mass and insulin sensitivity improved in men only, sleep quality was unchanged, and the only adverse effect was transient hyperlipidemia. Regulatory reviews summarize the pediatric trials that supported the 1997 Geref approval.", "animal_evidence": "Preclinical work in rats and other species established that GHRH(1-29) is the minimal fragment with full GH releasing activity and that its effect depends on an intact pituitary. Animal data are mainly mechanistic and supported the human pharmacology rather than any independent claim.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Geref label (pediatric idiopathic GH deficiency): 30 ug/kg subcutaneously once daily at bedtime. Geref diagnostic: 1 ug/kg as a single intravenous dose. Khorram 1997 adult trial: 10 ug/kg subcutaneously nightly for 16 weeks. Kirk 1994: 20 ug/kg subcutaneously twice daily for 12 months in children. No dose has been established for adult anti-aging, body composition, or sleep use.", "routes": [ "Subcutaneous injection, usually at bedtime (approved and trial use)", "Intravenous bolus (former diagnostic use)", "Intranasal (research only, lower bioavailability)", "Oral tablets and troches sold by some compounders have no published pharmacokinetic data" ], "side_effects": [ "Injection site pain, redness, or swelling (most common in the pediatric trials)", "Facial flushing, headache, and dizziness after injection", "Transient hyperlipidemia in the adult trial, which resolved by study end", "Rising fasting glucose and insulin during treatment in children", "Antibody formation to sermorelin was reported in the pediatric program without apparent loss of effect", "Theoretical GH related effects (fluid retention, joint pain, carpal tunnel, reduced insulin sensitivity) at higher exposures" ], "interactions": [ "Glucocorticoids, particularly at supraphysiologic doses, blunt the GH response to GHRH", "Somatostatin analogs (octreotide, lanreotide) directly oppose GH release", "Insulin and diabetes medications: GH raises glucose and may change requirements", "Levothyroxine: untreated hypothyroidism reduces the GH response; thyroid status should be normal before use", "Cyclooxygenase inhibitors and antimuscarinic drugs can alter GH release in provocative testing" ], "contraindications": [ "Hypersensitivity to sermorelin or the formulation", "Active malignancy (GH and IGF-1 are growth promoting; no human safety data)", "Pregnancy and breastfeeding (no data)", "Untreated hypothyroidism (blunts response)", "Competitive athletes subject to WADA testing (prohibited under S2)" ], "wada_status": "prohibited", "fda_status": "unknown", "compounding_status": "There is no currently approved sermorelin product in the United States. Geref (sermorelin acetate) was approved as a diagnostic on December 28, 1990 (NDA 19-863) and for treatment of idiopathic growth hormone deficiency in children on September 26, 1997 (NDA 20-443); the sponsor discontinued both in 2008 and FDA withdrew the approvals effective June 18, 2009. In March 2013 FDA determined in the Federal Register that Geref was not withdrawn for reasons of safety or effectiveness, which allows generic applications. Sermorelin was not placed on the 503A Category 2 list in 2023 and is not on the 503A bulks list; many 503A pharmacies compound it on the basis of the former approval, and whether that satisfies the component of an approved drug condition depends on how a state board and the pharmacy read it. Compounded sermorelin for adult anti-aging, fat loss, or sleep is an unapproved use with no supporting trial.", "typical_cost": "About 105 to 180 USD per month for compounded sermorelin through licensed telehealth programs, including the consultation and medication. Research chemical listings are not lawful for human use. Prices checked 2026-09-22 on published provider and pharmacy price pages.", "access_path": [ "Prescription from a licensed provider filled by a state licensed 503A compounding pharmacy, commonly through telehealth clinics.", "No FDA approved product is currently marketed (Geref was withdrawn in 2009).", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is sermorelin FDA approved or legal?", "a": "It was. Geref (sermorelin acetate) was FDA approved in 1990 as a diagnostic and in 1997 to treat GH deficiency in children, but the manufacturer discontinued it and FDA withdrew the approvals in 2009. FDA later confirmed the withdrawal was not for safety or effectiveness. Today there is no approved product; sermorelin is prescribed and compounded (custom-made) by 503A pharmacies, which compound for individual patients, and it was not placed on FDA's 2023 Category 2 list of compounding ingredients with significant safety risks. Possessing it is not a crime, but research chemical versions are not lawful for human use.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "q": "Does sermorelin work?", "a": "It reliably raises the body's own growth hormone and IGF-1; several small human studies show that. Evidence for the results people want is thin. The only placebo controlled adult trial had 19 people aged 55 to 71 treated nightly for 16 weeks: skin thickness increased in both sexes, and men (not women) gained lean body mass and insulin sensitivity. Body weight, blood pressure, and bone density did not change and sleep quality was unaffected. That is evidence of a hormonal effect with modest, sex dependent physical changes, not proof of anti-aging or meaningful muscle gain.", "source_ids": [ "khorram-1997", "corpas-1992", "vance-1986" ] }, { "q": "Sermorelin before and after: what did trials actually measure?", "a": "Hormones and body composition, not appearance. In 10 healthy older men, two weeks of twice daily injections at the higher of two doses raised 24 hour GH and IGF-1 to levels seen in young men. In 19 adults aged 55 to 71, 16 weeks of nightly injections raised IGF-1 within 2 weeks, thickened skin, and added lean mass in men only, with no change in weight or bone density. In 11 older men, 6 weeks of nightly injections improved 2 of 6 strength measures without changing muscle or fat on DEXA, in a study with no placebo group. Before and after photos and testimonials are not trial data.", "source_ids": [ "corpas-1992", "khorram-1997", "vittone-1997" ] }, { "q": "Sermorelin reviews: what does the evidence say?", "a": "Published reviews describe sermorelin as an effective growth hormone stimulant that was approved for children with growth hormone deficiency. A 2006 review proposed it for adult-onset growth hormone insufficiency, but the adult trials behind that idea enrolled 20 or fewer people each and ran 2 to 16 weeks. None tested anti-aging, fat loss, or sleep as a primary outcome in a large controlled trial. Clinic testimonials and online ratings are not controlled evidence.", "source_ids": [ "prakash-1999", "walker-2006", "khorram-1997", "vittone-1997" ] }, { "q": "What are the side effects of sermorelin?", "a": "In trials the common effects were injection site pain or redness, facial flushing, headache, and dizziness. The adult trial reported transient hyperlipidemia that resolved, and the pediatric study saw rises in fasting glucose and insulin during treatment. Because sermorelin raises GH and IGF-1, the theoretical concerns of GH therapy (fluid retention, joint pain, insulin resistance, growth of existing tumors) apply, though no long term adult safety study exists.", "source_ids": [ "khorram-1997", "kirk-1994" ] }, { "q": "Is sermorelin an injection or a pill?", "a": "The approved product, Geref, was an injection, and the adult trials used injections under the skin, usually at bedtime. A 1986 study found intranasal sermorelin raised growth hormone only weakly, releasing about a fifth as much as an intravenous dose even when far more was given. Some compounders sell troches, tablets, or nasal sprays; no published trial shows those forms produce the effects seen with injections.", "source_ids": [ "prakash-1999", "khorram-1997", "vance-1986" ] }, { "q": "How much does sermorelin cost?", "a": "Compounded sermorelin through licensed telehealth programs costs about 105 to 180 USD per month including the prescriber consultation, depending on plan length. There is no branded product and no insurance coverage for adult off-label use. Prices were checked on 2026-09-22 and change often.", "source_ids": [ "price-telehealth-sermorelin-a", "price-telehealth-sermorelin-b", "fda-503a-bulks" ] }, { "q": "Is sermorelin banned by WADA?", "a": "Yes. Sermorelin is named explicitly in section S2 of the WADA Prohibited List (growth hormone releasing hormone and its analogues, alongside CJC-1295 and tesamorelin) and is prohibited at all times, in and out of competition. Tested athletes should not use it.", "source_ids": [ "wada-list" ] }, { "q": "Sermorelin vs ipamorelin vs CJC-1295: what is the difference?", "a": "Sermorelin and CJC-1295 are both GHRH analogs that act on the GHRH receptor; sermorelin lasts minutes, CJC-1295 with DAC lasts about a week. Ipamorelin is a ghrelin receptor agonist that releases GH through a different receptor and is often stacked with a GHRH analog. Sermorelin is the only one that was ever FDA approved and the only one currently compounded by licensed pharmacies without a Category 2 history; ipamorelin and CJC-1295 were placed in Category 2 in 2023 and later listed as withdrawn nominations.", "source_ids": [ "walker-2006", "fda-503a-bulks" ] }, { "q": "Does sermorelin help you sleep?", "a": "Not according to the trial data. In the 16 week adult study, sleep quality measured by questionnaire did not change in either sex, even though nocturnal GH rose. Claims that sermorelin improves deep sleep are extrapolated from GH physiology, not from a sermorelin sleep trial.", "source_ids": [ "khorram-1997" ] } ], "studies": [ { "pmid": "9141536", "title": "Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women", "year": 1997, "design": "Single blind, randomized, placebo controlled trial, 4 weeks placebo then 16 weeks active, nightly subcutaneous injection", "n": 19, "population": "Healthy men and women aged 55 to 71", "outcome": "Increased 12 hour nocturnal GH, IGF-1, and IGFBP-3; increased skin thickness in both sexes; increased lean mass, insulin sensitivity, well being, and libido in men only; sleep unchanged; transient hyperlipidemia", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9141536/" }, { "pmid": "7955460", "title": "Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity", "year": 1994, "design": "Open label, single arm, 12 month treatment study with pre and post treatment comparison", "n": 18, "population": "Prepubertal children aged 4 to 11 with idiopathic short stature (not GH deficient)", "outcome": "Mean height velocity rose from 4.8 to 7.2 cm per year (p = 0.001) on 20 ug/kg twice daily; catch down growth after stopping; fasting glucose and insulin rose", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/7955460/" }, { "pmid": "3096623", "title": "The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships", "year": 1986, "design": "Dose response pharmacology study in healthy volunteers", "population": "Healthy adult men", "outcome": "GH release after intravenous, subcutaneous, and intranasal dosing with dose dependent responses; intranasal route least potent", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/3096623/" }, { "pmid": "18031173", "title": "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency", "year": 1999, "design": "Drug evaluation review", "population": "Children with idiopathic GH deficiency in the registration trials", "outcome": "Summarizes growth velocity gains with 30 ug/kg daily and the tolerability profile (injection site reactions, flushing, headache) that supported the 1997 approval", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18031173/" }, { "pmid": "18046908", "title": "Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?", "year": 2006, "design": "Narrative review and opinion", "population": "Adults with age related decline in GH secretion", "outcome": "Argues that GHRH analog therapy preserves feedback regulation compared with recombinant GH; presents no new trial data", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/18046908/" }, { "pmid": "1379256", "title": "Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men", "year": 1992, "design": "Randomized crossover of two dose levels, 14 days each, with a young male comparison group", "n": 19, "population": "Healthy old men (n = 10) compared with healthy young men (n = 9)", "outcome": "At the higher dose, 24 hour GH and IGF-1 in old men rose to levels not different from young men; no change in fasting glucose or blood pressure", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/1379256/" }, { "pmid": "9005976", "title": "Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men", "year": 1997, "design": "Uncontrolled before and after study, 6 weeks", "n": 11, "population": "Healthy non-obese men aged 64 to 76 with low baseline IGF-1", "outcome": "Nocturnal GH rose without a change in IGF-1; 2 of 6 strength measures and one endurance test improved; no change in DEXA muscle or fat, weight, glucose, or lipids", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9005976/" } ], "sources": [ { "id": "khorram-1997", "type": "pubmed", "title": "Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/9141536/", "pmid": "9141536", "year": 1997 }, { "id": "kirk-1994", "type": "pubmed", "title": "Kirk JM et al. Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clin Endocrinol (Oxf) 1994", "url": "https://pubmed.ncbi.nlm.nih.gov/7955460/", "pmid": "7955460", "year": 1994 }, { "id": "vance-1986", "type": "pubmed", "title": "Vance ML et al. The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships. Clin Pharmacol Ther 1986", "url": "https://pubmed.ncbi.nlm.nih.gov/3096623/", "pmid": "3096623", "year": 1986 }, { "id": "prakash-1999", "type": "pubmed", "title": "Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/18031173/", "pmid": "18031173", "year": 1999 }, { "id": "walker-2006", "type": "pubmed", "title": "Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/18046908/", "pmid": "18046908", "year": 2006 }, { "id": "fr-geref-2013", "type": "federal_register", "title": "Federal Register, March 4, 2013: Determination that Geref (sermorelin acetate) injection was not withdrawn from sale for reasons of safety or effectiveness (NDA 19-863 and NDA 20-443)", "url": "https://www.govinfo.gov/content/pkg/FR-2013-03-04/html/2013-04827.htm", "year": 2013 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (503A bulks list, Category 1, 2, and 3 lists)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, including sermorelin)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-telehealth-sermorelin-a", "type": "other", "title": "Licensed telehealth provider price page for compounded sermorelin, accessed 2026-09-22", "url": "https://trynovamd.com/sermorelin" }, { "id": "price-telehealth-sermorelin-b", "type": "other", "title": "Second licensed telehealth provider price page for compounded sermorelin, accessed 2026-09-22", "url": "https://precisiontelemed.com/sermorelin/" }, { "id": "corpas-1992", "type": "pubmed", "title": "Corpas E et al. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab 1992", "url": "https://pubmed.ncbi.nlm.nih.gov/1379256/", "pmid": "1379256", "year": 1992 }, { "id": "vittone-1997", "type": "pubmed", "title": "Vittone J et al. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/9005976/", "pmid": "9005976", "year": 1997 } ], "related": [ "tesamorelin", "cjc-1295", "ipamorelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Sermorelin: evidence, results, and legal status", "description": "Sermorelin, the GHRH 1-29 peptide once approved as Geref: what trials measured before and after, side effects, and its US legal status.", "headings": { "evidence": "Sermorelin before and after: what trials measured", "safety": "Sermorelin side effects" } } }, { "slug": "ipamorelin", "name": "Ipamorelin", "aliases": [ "Ipamorelin acetate", "NNC 26-0161", "Aib-His-D-2-Nal-D-Phe-Lys-NH2", "CJC-1295/ipamorelin blend" ], "class": "Synthetic pentapeptide growth hormone secretagogue; selective agonist at the ghrelin receptor (GHS-R1a)", "one_liner": "Growth hormone releaser acting on the hunger hormone (ghrelin) receptor; raised GH in animals and one small study in men; its only randomized trial failed.", "summary": "Ipamorelin is a five amino acid ghrelin receptor agonist (it activates the receptor for the hunger hormone ghrelin) developed in the 1990s as a growth hormone secretagogue, a drug that makes the pituitary release growth hormone, that unlike GHRP-2 and GHRP-6 does not raise cortisol or prolactin in animals. The only randomized human trial tested it for postoperative ileus (the gut stalling after bowel surgery) and found no significant benefit. One small pharmacology study showed a single IV (into a vein) infusion releases GH in healthy men, but there is no human trial of ipamorelin for GH deficiency, body composition, recovery, or sleep, which are the uses it is sold for. FDA placed it on the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in September 2023, the nominators withdrew it in 2024, and it is now listed as a withdrawn nomination with no lawful basis for compounding (custom-making by a pharmacy).", "mechanism": "Ipamorelin binds the growth hormone secretagogue receptor (GHS-R1a, the ghrelin receptor) on pituitary somatotrophs and hypothalamic neurons, triggering GH release through a pathway separate from GHRH. In rats and pigs its potency and efficacy for GH release matched GHRP-6, but it did not raise ACTH, cortisol, prolactin, LH, FSH, or TSH even at doses 200 fold above the GH ED50. Ghrelin receptor activation also stimulates gastric motility, which is why it was later tested for postoperative ileus.", "evidence_grade": "animal_only", "evidence_summary": "For the uses ipamorelin is marketed for (GH release for muscle, fat loss, recovery, anti-aging, sleep) the evidence is animal and in vitro only: rat, pig, and cell studies show selective GH release and rat studies show increased bone growth. The one randomized, double blind, placebo controlled human trial (n = 117) tested intravenous ipamorelin for postoperative ileus and found no significant difference from placebo in time to first tolerated meal (25.3 versus 32.6 hours, p = 0.15); it did show the drug was well tolerated over up to 7 days. Development stopped after that trial. One small human pharmacology study (40 healthy men, five IV infusion rates) found GH release at every dose, but no human study reports GH, IGF-1, or body composition outcomes with the subcutaneous doses sold today. That trial used intravenous ipamorelin for a surgical indication, not the subcutaneous product as marketed; it is listed but does not raise the grade.", "human_evidence": "Beck 2014 (Ipamorelin 201 Study Group): 117 adults enrolled after small or large bowel resection, 114 analyzed, randomized to 0.03 mg/kg intravenous ipamorelin or placebo twice daily on postoperative days 1 to 7. Median time to first tolerated solid meal was 25.3 hours with ipamorelin versus 32.6 hours with placebo (p = 0.15); secondary endpoints also did not differ. Treatment emergent adverse events occurred in 87.5% of the ipamorelin group and 94.8% of placebo, with no safety signal. A 1999 dose escalation study in 40 healthy men found that a single 15 minute IV infusion released GH at all five infusion rates, with a terminal half-life of about 2 hours; no published trial measures GH or IGF-1 responses to the subcutaneous doses used outside research. No indexed human trial for GH deficiency, body composition, or sleep identified.", "animal_evidence": "Raun 1998: in rat pituitary cells ipamorelin released GH with potency similar to GHRP-6; in anesthetized rats and conscious pigs it released GH with comparable efficacy while, unlike GHRP-2 and GHRP-6, not raising ACTH or cortisol. Johansen 1999: ipamorelin increased longitudinal bone growth in rats. Venkova 2009 and Greenwood-Van Meerveld 2012: ipamorelin accelerated gastric emptying and reversed delayed transit in rodent models of postoperative ileus, which motivated the human trial.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Not established in human literature for GH related use. The only human RCT used 0.03 mg/kg intravenously twice daily for up to 7 days for postoperative ileus. Animal GH release studies used nanomole per kilogram intravenous doses (rat ED50 about 80 nmol/kg; pig ED50 about 2.3 nmol/kg). No human dose finding study for subcutaneous ipamorelin has been published.", "routes": [ "Subcutaneous injection (as sold, no human pharmacokinetic publication)", "Intravenous infusion (human ileus trial)", "Intranasal (anti-doping metabolite study only)" ], "side_effects": [ "No safety signal versus placebo in the 7 day intravenous ileus trial (adverse events 87.5% versus 94.8%, mostly surgical)", "Injection site reactions, headache, flushing, and lightheadedness reported anecdotally", "Increased appetite (ghrelin receptor effect) reported anecdotally", "FDA cited immunogenicity risk from aggregation and impurities and limited safety data by the routes used in compounding when it placed ipamorelin in Category 2", "Theoretical GH and IGF-1 related effects (fluid retention, insulin resistance, growth of existing tumors) untested in humans at marketed doses" ], "interactions": [ "No formal human interaction studies exist", "Glucocorticoids and somatostatin analogs blunt GH release from any secretagogue", "Diabetes medications: GH raises glucose, so a theoretical effect on insulin requirements exists", "Often sold blended with CJC-1295; the combination has never been tested in humans" ], "contraindications": [ "Active malignancy (GH and IGF-1 are growth promoting; no human safety data)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (named in section S2)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Not FDA approved for any use and never approved anywhere. FDA placed ipamorelin (free base and acetate) on the 503A Category 2 list on September 29, 2023, citing immunogenicity risk, peptide related impurities, and lack of safety data for the compounded routes. The nominators withdrew the 503A nominations in September 2024 and FDA's April 2026 update moved it to the list of nominated but withdrawn substances rather than Category 1 or the bulks list. Ipamorelin acetate also remains in 503B Category 2 (added September 29, 2023) on the FDA page current as of April 22, 2026. It was not among the peptides the Pharmacy Compounding Advisory Committee reviewed in July 2026. Because it has no active nomination, is not on the 503A bulks list, and is not a component of an approved drug, licensed 503A pharmacies and 503B outsourcing facilities have no lawful basis to compound it.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available through a licensed pharmacy (no active 503A nomination, not on the bulks list, not an approved drug).", "Clinics that still advertise compounded ipamorelin are dispensing outside FDA's stated categories; ask what the legal basis is.", "Products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "What is ipamorelin?", "a": "Ipamorelin is a synthetic five amino acid peptide that activates the ghrelin receptor (the receptor for the hunger hormone ghrelin) and makes the pituitary gland release growth hormone. Developed in the 1990s, it was described as the first selective growth hormone secretagogue (growth hormone releaser) because in animals it released growth hormone without raising cortisol or prolactin. In people it was tested only for bowel recovery after surgery, where it did not help, and it has never been approved.", "source_ids": [ "raun-1998", "beck-2014" ] }, { "q": "Is ipamorelin legal in the United States?", "a": "It is not an FDA approved drug and cannot lawfully be compounded. FDA put ipamorelin on the 503A Category 2 list (substances with significant safety risks) in September 2023, the companies that nominated it withdrew those nominations in 2024, and in April 2026 FDA moved it to the list of withdrawn nominations. That is not a listing on the 503A bulks list, so pharmacies have no legal basis to compound it. Possession is not a crime, but research chemical versions are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Ipamorelin benefits: what does the evidence show?", "a": "Nobody has tested it. In rats and pigs ipamorelin releases GH about as well as GHRP-6, and in rats it increased bone growth. In humans the only randomized trial tested it for bowel recovery after surgery, not body composition, and it was negative. One small study found a single IV infusion releases GH in healthy men, but no published trial measures GH, IGF-1, muscle, or fat changes from the subcutaneous doses sold today, so PeptideAgent grades the evidence for the marketed uses animal-only.", "source_ids": [ "raun-1998", "johansen-1999", "beck-2014", "gobburu-1999" ] }, { "q": "What are the side effects of ipamorelin?", "a": "In the only human RCT, 7 days of intravenous ipamorelin after bowel surgery produced no more adverse events than placebo (87.5% versus 94.8%, mostly surgical). Anecdotal reports with subcutaneous use mention injection site reactions, headache, flushing, lightheadedness, and increased appetite. FDA's Category 2 evaluation flagged immunogenicity risk from peptide aggregation and impurities. Long term effects of raising GH this way in adults are unstudied.", "source_ids": [ "beck-2014", "fda-503a-bulks" ] }, { "q": "How much does ipamorelin cost?", "a": "There is no lawful licensed channel, so there is no legitimate price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is ipamorelin banned by WADA?", "a": "Yes. Ipamorelin is named in section S2 of the WADA Prohibited List under growth hormone secretagogues (with GHRP-2, GHRP-6, hexarelin, and ibutamoren) and is prohibited at all times. Anti-doping laboratories have published methods to detect it and its metabolites in urine.", "source_ids": [ "wada-list", "semenistaya-2015" ] }, { "q": "Ipamorelin vs CJC-1295: what is the difference and why are they combined?", "a": "They act on different receptors. Ipamorelin is a ghrelin receptor agonist; CJC-1295 is a long acting GHRH analog. In theory activating both pathways releases more GH than either alone, which is why clinics sold them blended, but that combination has never been tested in a human trial. CJC-1295 has small human RCTs showing sustained GH and IGF-1 increases; ipamorelin has only one small IV pharmacology study of GH release in healthy men. Both were placed in Category 2 in 2023 and both are now withdrawn nominations, so neither can be lawfully compounded.", "source_ids": [ "raun-1998", "fda-503a-bulks", "gobburu-1999" ] }, { "q": "Why is ipamorelin called the cleanest GH secretagogue?", "a": "Because of the 1998 animal pharmacology. In pigs, GHRP-2 and GHRP-6 raised ACTH and cortisol along with GH, while ipamorelin released GH without raising ACTH, cortisol, prolactin, LH, FSH, or TSH, even at very high doses. That selectivity is real in animals, but it has not been confirmed in a human trial at the doses people use.", "source_ids": [ "raun-1998" ] } ], "studies": [ { "pmid": "25331030", "title": "Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients", "year": 2014, "design": "Multicenter, randomized, double blind, placebo controlled phase 2 trial, intravenous dosing up to 7 days", "n": 117, "population": "Adults after open or laparoscopic small or large bowel resection", "outcome": "Median time to first tolerated meal 25.3 hours versus 32.6 hours with placebo (p = 0.15); no significant difference on any efficacy endpoint; well tolerated", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25331030/" }, { "pmid": "9849822", "title": "Ipamorelin, the first selective growth hormone secretagogue", "year": 1998, "design": "In vitro rat pituitary cell assays plus in vivo studies in anesthetized rats and conscious pigs", "population": "Rat pituitary cells, rats, and pigs", "outcome": "GH release comparable to GHRP-6 (pig ED50 2.3 nmol/kg) with no increase in ACTH, cortisol, prolactin, LH, FSH, or TSH", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" }, { "pmid": "10373343", "title": "Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats", "year": 1999, "design": "Controlled animal study", "population": "Rats", "outcome": "Increased longitudinal bone growth and IGF-1 related markers with repeated dosing", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/10373343/" }, { "pmid": "19289567", "title": "Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus", "year": 2009, "design": "Controlled animal study", "population": "Rats with surgically induced postoperative ileus", "outcome": "Ipamorelin accelerated gastric emptying and intestinal transit, motivating the later human trial", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/19289567/" }, { "pmid": "10496658", "title": "Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers", "year": 1999, "design": "Dose escalation pharmacokinetic and pharmacodynamic study, five IV infusion rates", "n": 40, "population": "Healthy men (8 per dose level)", "outcome": "A single 15 minute IV infusion released GH at all dose levels, with a single GH peak at about 0.67 hours and a terminal half-life of about 2 hours; no clinical or body composition outcome", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/10496658/" } ], "sources": [ { "id": "beck-2014", "type": "pubmed", "title": "Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25331030/", "pmid": "25331030", "year": 2014 }, { "id": "raun-1998", "type": "pubmed", "title": "Raun K et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/", "pmid": "9849822", "year": 1998 }, { "id": "johansen-1999", "type": "pubmed", "title": "Johansen PB et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10373343/", "pmid": "10373343", "year": 1999 }, { "id": "venkova-2009", "type": "pubmed", "title": "Venkova K et al. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19289567/", "pmid": "19289567", "year": 2009 }, { "id": "semenistaya-2015", "type": "pubmed", "title": "Semenistaya E et al. Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, hexarelin, and ipamorelin. Drug Test Anal 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25869809/", "pmid": "25869809", "year": 2015 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (503A bulks list, Category 1, 2, and 3 lists, and withdrawn nominations)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone secretagogues, including ipamorelin)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "gobburu-1999", "type": "pubmed", "title": "Gobburu JV et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10496658/", "pmid": "10496658", "year": 1999 } ], "related": [ "cjc-1295", "sermorelin", "ghrp-2", "ghrp-6" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 4, "seo": { "title": "Ipamorelin: benefits, side effects, and legal status", "description": "Ipamorelin benefits and side effects, graded: animal GH data, one negative human trial, and why no US pharmacy can lawfully compound it.", "headings": { "evidence": "Ipamorelin benefits: what the evidence shows", "safety": "Ipamorelin side effects" } } }, { "slug": "cjc-1295", "name": "CJC-1295", "aliases": [ "CJC-1295 with DAC", "CJC-1295 DAC", "DAC:GRF", "Modified GRF (1-29) (marketed as CJC-1295 without DAC)", "Tetrasubstituted GHRH(1-29)", "CJC-1295/ipamorelin blend", "CJC-1295 without DAC", "Mod GRF 1-29", "CJC peptide" ], "class": "Synthetic 29 amino acid GHRH(1-29) analog with four stabilizing amino acid substitutions and a drug affinity complex (maleimidoproprionic acid) that binds covalently to circulating albumin", "one_liner": "Long acting lab-made growth hormone releasing hormone: small randomized trials raised GH 2 to 10 fold and IGF-1 1.5 to 3 fold per dose; no lawful compounding.", "summary": "CJC-1295 is a GHRH(1-29) analog, a lab-made version of the hormone that tells the pituitary gland to release growth hormone (GH), engineered to bind albumin (the main protein in blood) so that one injection stimulates GH for about a week. Two small randomized, placebo controlled trials (people assigned by chance to the drug or a dummy injection) in healthy adults showed dose dependent GH increases of 2 to 10 fold for 6 or more days and IGF-1 (a growth factor that GH raises) increases of 1.5 to 3 fold for 9 to 11 days after a single injection under the skin, with a half life (time for half the drug to clear) of 5.8 to 8.1 days. It was never approved anywhere, development stopped in the late 2000s, FDA placed it on the 503A Category 2 list (compounding ingredients flagged for significant safety risks) in September 2023, and it is now a withdrawn nomination with no lawful basis for compounding (custom-making by a pharmacy).", "mechanism": "CJC-1295 activates the pituitary GHRH receptor like native GHRH, increasing GH synthesis and release and downstream hepatic IGF-1. Four substitutions (D-Ala2, Gln8, Ala15, Leu27) protect it from dipeptidyl peptidase IV and other proteases, and the reactive DAC group forms a covalent bond with serum albumin within minutes of injection, extending the half life from minutes to about a week. In healthy men, GH pulsatility was preserved but trough GH levels rose 7.5 fold, which drove the increase in IGF-1. The version sold as CJC-1295 without DAC lacks the albumin linker and has a half life of about 30 minutes; it has no published human trials under that name.", "evidence_grade": "human_rct", "evidence_summary": "Evidence is limited to small phase 1 and 2 pharmacology trials in healthy adults with hormonal endpoints. Teichman 2006 ran two randomized, placebo controlled, double blind ascending dose studies (28 and 49 days) in healthy adults aged 21 to 61: a single injection raised mean GH 2 to 10 fold for 6 or more days and IGF-1 1.5 to 3 fold for 9 to 11 days, with IGF-1 staying above baseline for up to 28 days after repeated doses and no serious adverse reactions. Ionescu 2006 gave 60 or 90 ug/kg to healthy men aged 20 to 40 and found trough GH up 7.5 fold, mean GH up 46%, and IGF-1 up 45% one week later with preserved pulsatility. No trial has measured body composition, strength, fat loss, sleep, or any clinical outcome, and there is no long term safety data. Development for HIV lipodystrophy and GH deficiency was discontinued.", "human_evidence": "Teichman 2006: two randomized, placebo controlled, double blind ascending dose trials in healthy adults 21 to 61; single subcutaneous doses produced dose dependent GH increases of 2 to 10 fold lasting 6 or more days and IGF-1 increases of 1.5 to 3 fold lasting 9 to 11 days; half life 5.8 to 8.1 days; cumulative effect with weekly or biweekly dosing; best tolerated at 30 or 60 ug/kg. Ionescu 2006: healthy men 20 to 40, single dose of 60 or 90 ug/kg, overnight 20 minute sampling before and 1 week after; trough GH up 7.5 fold (p < 0.0001), mean GH up 46%, IGF-1 up 45%, pulse frequency and amplitude unchanged, no difference between doses. Sackmann-Sala 2009: serum proteomic changes consistent with GH and IGF-1 axis activation in normal adults. No trial with clinical endpoints has been published.", "animal_evidence": "Jette 2005 identified CJC-1295 among GHRH(1-29) albumin bioconjugates that activate the GRF receptor in rat pituitary and produce sustained GH and IGF-1 elevation in rats. Alba 2006 showed once daily CJC-1295 normalized growth, IGF-1, and pituitary GH content in GHRH knockout mice. These support the mechanism and duration of action but add nothing about efficacy for adult body composition.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Human pharmacology trials only: single subcutaneous doses in ascending cohorts, with 30 or 60 ug/kg described as best tolerated, and repeated weekly or biweekly dosing over 28 to 49 days (Teichman 2006); single doses of 60 or 90 ug/kg (Ionescu 2006). No maintenance dose, no trial longer than 49 days, and no dose for any clinical indication has been established. Doses advertised in milligrams per week for the version without DAC come from no human study.", "routes": [ "Subcutaneous injection (human trials and as sold)" ], "side_effects": [ "Injection site reactions (most common in trials)", "Flushing, headache, and transient warmth or vasodilation shortly after injection", "Increased heart rate and a systemic vasodilatory reaction were among the serious adverse events FDA cited in its Category 2 evaluation", "Water retention, tingling, and joint aches consistent with raised GH and IGF-1 reported in trials and anecdotally", "No serious adverse reactions in the two small 2006 trials; no long term safety data", "Theoretical risks of sustained IGF-1 elevation, including insulin resistance and growth of existing tumors, have not been studied" ], "interactions": [ "No formal human interaction studies exist", "Glucocorticoids and somatostatin analogs blunt GH release from GHRH analogs", "Diabetes medications: sustained GH raises glucose, so insulin or oral agent requirements could change", "Levothyroxine: untreated hypothyroidism reduces GH response", "Often sold blended with ipamorelin; the combination has never been tested in humans" ], "contraindications": [ "Active malignancy (sustained IGF-1 elevation; no human safety data)", "Pregnancy and breastfeeding (no data)", "Untreated hypothyroidism (blunts response)", "Competitive athletes subject to WADA testing (named in section S2)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Not FDA approved for any use and never approved anywhere; the developer's programs in HIV lipodystrophy and GH deficiency were discontinued in the late 2000s. FDA placed CJC-1295 on the 503A Category 2 list on September 29, 2023, citing limited clinical data, peptide related impurities, and serious adverse events including increased heart rate and a systemic vasodilatory reaction. The nomination was later withdrawn and FDA's April 2026 update lists CJC-1295 under nominated but withdrawn substances rather than Category 1 or the bulks list. It was not among the peptides the Pharmacy Compounding Advisory Committee reviewed in July 2026. With no active nomination, no bulks list entry, and no approved product, licensed 503A pharmacies and 503B facilities have no lawful basis to compound it. Products sold as CJC-1295 without DAC are a different molecule (modified GRF 1-29) with the same non-status.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available through a licensed pharmacy (withdrawn 503A nomination, not on the bulks list, not an approved drug).", "Clinics that still advertise compounded CJC-1295 are dispensing outside FDA's stated categories; ask what the legal basis is.", "Products labeled research use only are not lawful for human use." ], "faqs": [ { "q": "What is CJC-1295?", "a": "CJC-1295 is a synthetic growth hormone releasing hormone analog, a lab-made version of the hormone that tells the pituitary gland to release growth hormone: the first 29 amino acids of GHRH with four amino acid substitutions, linked to a drug affinity complex (DAC) that binds albumin, the main protein in blood, so one injection lasts about a week. It was developed as a long acting growth hormone stimulant, tested only in small trials in healthy adults, and never approved. The name is also used loosely for modified GRF (1-29), the version without DAC.", "source_ids": [ "teichman-2006", "jette-2005" ] }, { "q": "Is CJC-1295 legal in the United States?", "a": "It is not an FDA approved drug and cannot lawfully be compounded. FDA put CJC-1295 on the 503A Category 2 list in September 2023 because of limited clinical data, impurity concerns, and reported serious adverse events. The nomination was later withdrawn, and in April 2026 FDA moved it to the withdrawn nominations list, which is not the 503A bulks list. Possession is not a crime, but research chemical versions are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "CJC-1295 with DAC vs without DAC: what is the difference?", "a": "CJC-1295 with DAC is the molecule studied in humans: the drug affinity complex binds it to albumin so it lasts 5.8 to 8.1 days and one dose raises GH and IGF-1 for over a week. CJC-1295 without DAC is a marketing name for modified GRF (1-29), the same four substitution GHRH analog without the albumin linker; it lasts about 30 minutes and has no published human trials under that name. Both are GHRH analogs, both are WADA prohibited, and neither can be lawfully compounded.", "source_ids": [ "teichman-2006", "jette-2005" ] }, { "q": "Does CJC-1295 actually raise growth hormone?", "a": "Yes, that part is well documented in small trials. In two randomized, placebo controlled studies in healthy adults, one subcutaneous dose raised mean GH 2 to 10 fold for 6 or more days and IGF-1 1.5 to 3 fold for 9 to 11 days, and a separate study found trough GH up 7.5 fold and IGF-1 up 45% a week after a 60 or 90 ug/kg dose. What no trial shows is whether that translates into muscle gain, fat loss, better sleep, or any clinical benefit; those outcomes were never measured.", "source_ids": [ "teichman-2006", "ionescu-2006" ] }, { "q": "CJC-1295 results: how long do they take to show?", "a": "There is no trial-based answer for visible results. In the human studies, growth hormone and IGF-1 rose after a single injection, IGF-1 stayed elevated for 9 to 11 days, and repeated doses kept IGF-1 above baseline for up to 28 days. No trial measured muscle, fat, recovery, or sleep, alone or combined with ipamorelin, so timelines quoted online are not from studies.", "source_ids": [ "teichman-2006", "ionescu-2006" ] }, { "q": "What are the side effects of CJC-1295?", "a": "In the two small 2006 trials the main effects were injection site reactions, flushing, headache, and transient warmth, with no serious adverse reactions and best tolerability at 30 or 60 ug/kg. FDA's Category 2 evaluation cited serious adverse events including increased heart rate and a systemic vasodilatory reaction and noted the overall clinical data are thin. Because one dose raises IGF-1 for over a week, the concerns of sustained GH excess (water retention, joint pain, insulin resistance, tumor growth) apply, and there is no long term safety study.", "source_ids": [ "teichman-2006", "fda-503a-bulks" ] }, { "q": "How much does CJC-1295 cost?", "a": "There is no lawful licensed channel, so there is no legitimate price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is CJC-1295 banned by WADA?", "a": "Yes. CJC-1295 is named explicitly in section S2 of the WADA Prohibited List under growth hormone releasing hormone and its analogues, together with sermorelin and tesamorelin, and is prohibited at all times. Anti-doping laboratories have identified it in seized preparations and developed detection methods.", "source_ids": [ "wada-list", "henninge-2010" ] }, { "q": "CJC-1295 vs sermorelin: which is better?", "a": "They hit the same receptor. Sermorelin is the unmodified GHRH(1-29) fragment with a half life of minutes and a former FDA approval, and it can still be compounded by 503A pharmacies. CJC-1295 lasts about a week per dose, produces larger and more sustained IGF-1 increases in trials, but was never approved, carries FDA cited serious adverse events, and cannot be lawfully compounded after the 2023 Category 2 listing. Neither has a trial showing muscle, fat, or performance benefits in adults.", "source_ids": [ "teichman-2006", "fda-503a-bulks" ] } ], "studies": [ { "pmid": "16352683", "title": "Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults", "year": 2006, "design": "Two randomized, placebo controlled, double blind ascending dose trials, 28 and 49 days, single and repeated subcutaneous doses", "population": "Healthy adults aged 21 to 61", "outcome": "Mean GH up 2 to 10 fold for 6 or more days and IGF-1 up 1.5 to 3 fold for 9 to 11 days after one dose; half life 5.8 to 8.1 days; IGF-1 above baseline up to 28 days with repeated dosing; no serious adverse reactions", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/" }, { "pmid": "17018654", "title": "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog", "year": 2006, "design": "Single dose pharmacodynamic study with overnight 20 minute sampling before and 1 week after injection", "population": "Healthy men aged 20 to 40", "outcome": "Trough GH up 7.5 fold (p < 0.0001), mean GH up 46%, IGF-1 up 45%; pulse frequency and amplitude unchanged; no difference between 60 and 90 ug/kg", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/" }, { "pmid": "19386527", "title": "Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects", "year": 2009, "design": "Proteomic analysis of serum from a CJC-1295 dosing study", "population": "Normal adult subjects", "outcome": "Serum protein changes consistent with GH and IGF-1 axis activation after CJC-1295", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/19386527/" }, { "pmid": "15817669", "title": "Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog", "year": 2005, "design": "In vitro receptor assays and in vivo rat pharmacology", "population": "Rat pituitary cells and rats", "outcome": "CJC-1295 bound albumin, activated the GRF receptor, and produced sustained GH and IGF-1 elevation in rats", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/15817669/" }, { "pmid": "16822960", "title": "Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse", "year": 2006, "design": "Controlled animal study", "population": "GHRH knockout mice", "outcome": "Daily CJC-1295 normalized body growth, IGF-1, and pituitary GH content", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/16822960/" } ], "sources": [ { "id": "teichman-2006", "type": "pubmed", "title": "Teichman SL et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16352683/", "pmid": "16352683", "year": 2006 }, { "id": "ionescu-2006", "type": "pubmed", "title": "Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/17018654/", "pmid": "17018654", "year": 2006 }, { "id": "sackmann-sala-2009", "type": "pubmed", "title": "Sackmann-Sala L et al. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19386527/", "pmid": "19386527", "year": 2009 }, { "id": "jette-2005", "type": "pubmed", "title": "Jette L et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15817669/", "pmid": "15817669", "year": 2005 }, { "id": "alba-2006", "type": "pubmed", "title": "Alba M et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16822960/", "pmid": "16822960", "year": 2006 }, { "id": "henninge-2010", "type": "pubmed", "title": "Henninge J et al. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Test Anal 2010", "url": "https://pubmed.ncbi.nlm.nih.gov/21204297/", "pmid": "21204297", "year": 2010 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (503A bulks list, Category 1, 2, and 3 lists, and withdrawn nominations)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, including CJC-1295)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ipamorelin", "sermorelin", "tesamorelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "CJC-1295 (with and without DAC): evidence and legality", "description": "CJC-1295 with DAC vs without DAC (mod GRF 1-29): what small human trials showed, side effects, and why no US pharmacy can lawfully compound it.", "h1": "CJC-1295 (with and without DAC)", "headings": { "evidence": "CJC-1295 with and without DAC: what the evidence shows" } } }, { "slug": "ghrp-2", "name": "GHRP-2", "aliases": [ "Growth hormone releasing peptide-2", "Pralmorelin", "KP-102", "GHRP 2", "D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2" ], "class": "Synthetic hexapeptide growth hormone secretagogue (ghrelin receptor agonist)", "one_liner": "Lab-made peptide that triggers growth hormone through the hunger hormone (ghrelin) receptor; approved only as a diagnostic test in Japan; WADA prohibited.", "summary": "GHRP-2 (pralmorelin) is a synthetic six amino acid peptide that stimulates growth hormone release by activating the ghrelin (GHS-R1a) receptor, the receptor for the body's hunger hormone. Small human pharmacology studies (short studies of a drug's effects) show it reliably raises growth hormone, cortisol, and prolactin and increases food intake, and it is approved in Japan as a diagnostic test for growth hormone deficiency, but there is no approved therapeutic use anywhere and no controlled trial of long term use in adults. FDA placed it in 503B Category 2 (ingredients flagged for significant safety risks in outsourcing facility compounding) in September 2023 for injectable and nasal routes, it has no 503A listing (the pathway for pharmacies compounding for individual patients), and it is prohibited by WADA.", "mechanism": "GHRP-2 binds the growth hormone secretagogue receptor (GHS-R1a), the same receptor as ghrelin, on pituitary somatotrophs and hypothalamic neurons. Activation triggers a pulse of growth hormone that is additive with GHRH, and it also raises ACTH, cortisol, and prolactin. Because it mimics ghrelin it increases hunger. It contains D amino acids and an unnatural amino acid (D-beta-naphthylalanine), which resist enzymatic breakdown.", "evidence_grade": "human_observational", "evidence_summary": "Human data consist of acute pharmacology studies and diagnostic test validation. Single doses of 1 ug/kg intravenous reliably release growth hormone in children and adults, a 2007 Japanese study established a 100 ug intravenous test with a peak GH cutoff of 9 ng/mL for diagnosing adult GH deficiency, and a placebo controlled crossover in 7 healthy men found a 1 ug/kg infusion raised food intake by about 36%. No randomized trial of chronic therapeutic use in adults has been published. The randomized crossover was a single dose physiology study of appetite, not a therapeutic trial; it is listed but does not raise the grade.", "human_evidence": "Pihoker 1995 (n = 34 short children) showed intravenous and intranasal GHRP-2 produced dose dependent GH release, with 1 ug/kg intravenously being a reliable stimulus. Arvat 1997 compared GHRP-2 and hexarelin in healthy adults and found both raised GH more than GHRH and also raised prolactin, ACTH, and cortisol. Laferrere 2005 gave 7 healthy men a 1 ug/kg per hour infusion in a double blind crossover and measured a 35.9% increase in ad libitum food intake. Chihara 2007 (n = 62 adults, plus controls) validated a 100 ug intravenous test for adult GH deficiency. Long term outcome data in adults are absent.", "animal_evidence": "GHRP-2 was developed from the original GHRP-6 series in rats and shown to release GH in rats, dogs, and primates and to act synergistically with GHRH. Rodent work established the ghrelin receptor as its target. Animal data are pharmacological rather than disease model based.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Diagnostic use only: single intravenous doses of 1 ug/kg in children (Pihoker 1995) and 100 ug in adults (Chihara 2007), or a 1 ug/kg per hour intravenous infusion in the food intake study (Laferrere 2005). No chronic therapeutic dose has been established in human literature; subcutaneous regimens sold online are not from any published trial.", "routes": [ "Intravenous bolus or infusion (diagnostic and research studies)", "Intranasal (research studies)", "Subcutaneous injection (as sold, not from published trials)" ], "side_effects": [ "Increased hunger (36% increase in food intake in a controlled study)", "Transient flushing, warmth, and sweating after intravenous dosing", "Rise in cortisol and prolactin with each dose", "Reduced insulin sensitivity and higher blood glucose (FDA cites reports of increased insulin requirements)", "FDA notes reports of pancreatitis, infection, and death in critically ill study subjects without established causality", "Water retention and numbness or tingling reported with growth hormone secretagogues generally" ], "interactions": [ "Insulin and oral diabetes medications: GH secretagogues raise blood glucose and can increase insulin requirements", "Glucocorticoids: GHRP-2 raises ACTH and cortisol, so stacking adds to steroid exposure", "GHRH analogs (sermorelin, CJC-1295, tesamorelin): synergistic GH release, untested for long term safety", "No formal human drug interaction studies exist" ], "contraindications": [ "Active cancer (GH and IGF-1 stimulation is a theoretical tumor growth concern)", "Diabetes or impaired glucose tolerance without monitoring", "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved for any use. FDA added GHRP-2 (for injectable and nasal routes) to the 503B Category 2 list on September 29, 2023, citing immunogenicity risk, an unnatural amino acid that complicates characterization, and reports of serious adverse events. As of the FDA page current to April 22, 2026, GHRP-2 remains in 503B Category 2 and has no 503A nomination or listing, so licensed compounding pharmacies have no lawful basis to compound it. It was not among the peptides withdrawn from Category 2 in April 2026. Pralmorelin is approved in Japan only as a diagnostic agent.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product; FDA placed GHRP-2 in 503B Category 2 on September 29, 2023 and it has no 503A nomination or listing.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is GHRP-2 legal in the United States?", "a": "It is not an FDA approved drug and cannot be lawfully compounded (custom-made by a pharmacy). FDA placed GHRP-2 in 503B Category 2 (substances with significant safety risks, under the rules for large outsourcing facilities) on September 29, 2023 for injectable and nasal use, and it has no 503A nomination (the pathway for pharmacies compounding for individual patients), so no licensed pharmacy can compound it. Possession is not a crime, but products sold as research chemicals are not lawful for human use. In Japan it is approved only as a diagnostic test for growth hormone deficiency.", "source_ids": [ "fda-category-2", "fda-503a-bulks", "chihara-2007" ] }, { "q": "Does GHRP-2 work for muscle growth or fat loss?", "a": "Nobody has tested that. The human studies are acute pharmacology and diagnostic studies: a single 1 ug/kg intravenous dose reliably releases a pulse of growth hormone, and GHRP-2 raises GH more than GHRH alone. There is no randomized trial measuring body composition, strength, or fat loss with repeated dosing in adults, so any such benefit is extrapolated from growth hormone physiology rather than shown.", "source_ids": [ "pihoker-1995", "arvat-1997" ] }, { "q": "What are the side effects of GHRP-2?", "a": "The best documented effect is hunger: in a double blind crossover, a 1 ug/kg per hour infusion raised food intake in healthy men by about 36%. Each dose also raises cortisol and prolactin. FDA's Category 2 rationale cites reports of increased insulin requirements, pancreatitis, infection, and deaths in critically ill study subjects, without established causality. Flushing and sweating are common after intravenous doses.", "source_ids": [ "laferrere-2005", "arvat-1997", "fda-category-2" ] }, { "q": "How is GHRP-2 taken?", "a": "In published studies it was given intravenously as a bolus (1 ug/kg in children, 100 ug in adults) or as an infusion, and intranasally in one pediatric study. Products sold online are subcutaneous injection vials, a route and schedule that has not been studied in any published human trial.", "source_ids": [ "pihoker-1995", "chihara-2007" ] }, { "q": "How much does GHRP-2 cost?", "a": "There is no licensed US price because no pharmacy can lawfully compound it. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is GHRP-2 banned by WADA?", "a": "Yes. Growth hormone secretagogues, including growth hormone releasing peptides such as GHRP-2, are prohibited at all times under section S2 of the WADA Prohibited List. GHRP-2 is one of the peptides most commonly detected in doping controls.", "source_ids": [ "wada-list" ] }, { "q": "GHRP-2 vs GHRP-6: what is the difference?", "a": "Both are synthetic hexapeptides acting on the ghrelin receptor. GHRP-2 is generally reported as the more potent GH releaser and is the one validated as a diagnostic test, while GHRP-6 was the original compound and produces the stronger hunger response in most reports. Both raise cortisol and prolactin, both are in FDA 503B Category 2 since September 2023, and both are WADA prohibited. Neither has long term human trial data.", "source_ids": [ "bowers-1998", "fda-category-2", "arvat-1997" ] }, { "q": "Is GHRP-2 the same as pralmorelin?", "a": "Yes. Pralmorelin (KP-102) is the international nonproprietary name for GHRP-2. Under that name it is approved in Japan as a single dose intravenous diagnostic test for growth hormone deficiency, which is the only regulatory approval the molecule holds anywhere.", "source_ids": [ "chihara-2007" ] } ], "studies": [ { "pmid": "7559885", "title": "Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature", "year": 1995, "design": "Dose response pharmacology study", "n": 34, "population": "Children with short stature", "outcome": "Intravenous 1 ug/kg and intranasal doses produced dose dependent GH release; intravenous route was the more reliable diagnostic stimulus", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/7559885/" }, { "pmid": "9285939", "title": "Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH", "year": 1997, "design": "Crossover pharmacology study in healthy volunteers", "population": "Healthy young adults", "outcome": "GHRP-2 and hexarelin released more GH than GHRH and also raised prolactin, ACTH, and cortisol", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9285939/" }, { "pmid": "15699539", "title": "Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men", "year": 2005, "design": "Double blind, placebo controlled crossover", "n": 7, "population": "Healthy lean men", "outcome": "A 1 ug/kg per hour intravenous infusion increased ad libitum food intake by 35.9% versus saline", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/15699539/" }, { "pmid": "17609397", "title": "A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency", "year": 2007, "design": "Diagnostic validation study", "n": 62, "population": "Adults with suspected GH deficiency and healthy controls in Japan", "outcome": "A 100 ug intravenous GHRP-2 test with a peak GH cutoff of 9 ng/mL discriminated severe adult GH deficiency", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/17609397/" }, { "pmid": "9893708", "title": "Growth hormone-releasing peptide (GHRP)", "year": 1998, "design": "Narrative review by the discoverer of the GHRP series", "population": "Animal and human pharmacology of GHRP-6, GHRP-2, and related peptides", "outcome": "Summarizes receptor mechanism, synergy with GHRH, and human GH release data", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9893708/" } ], "sources": [ { "id": "pihoker-1995", "type": "pubmed", "title": "Pihoker C et al. Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature. J Clin Endocrinol Metab 1995", "url": "https://pubmed.ncbi.nlm.nih.gov/7559885/", "pmid": "7559885", "year": 1995 }, { "id": "arvat-1997", "type": "pubmed", "title": "Arvat E et al. Effects of GHRP-2 and hexarelin on GH, prolactin, ACTH and cortisol levels in man. Peptides 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/9285939/", "pmid": "9285939", "year": 1997 }, { "id": "laferrere-2005", "type": "pubmed", "title": "Laferrere B et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. J Clin Endocrinol Metab 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15699539/", "pmid": "15699539", "year": 2005 }, { "id": "chihara-2007", "type": "pubmed", "title": "Chihara K et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Eur J Endocrinol 2007", "url": "https://pubmed.ncbi.nlm.nih.gov/17609397/", "pmid": "17609397", "year": 2007 }, { "id": "bowers-1998", "type": "pubmed", "title": "Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9893708/", "pmid": "9893708", "year": 1998 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ghrp-6", "hexarelin", "ipamorelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "ghrp-6", "name": "GHRP-6", "aliases": [ "Growth hormone releasing peptide-6", "GHRP 6", "SKF-110679", "His-D-Trp-Ala-Trp-D-Phe-Lys-NH2" ], "class": "Synthetic hexapeptide growth hormone secretagogue (ghrelin receptor agonist), the first of the GHRP series", "one_liner": "Original lab-made growth hormone releasing peptide: raises GH and hunger in small human studies; never approved; on an FDA compounding risk list; WADA banned.", "summary": "GHRP-6 is a synthetic six amino acid peptide first described in 1984 that releases growth hormone by activating the ghrelin receptor (the receptor for the body's hunger hormone), years before ghrelin itself was discovered. Small human pharmacology studies show it releases GH, raises the stress hormones ACTH and cortisol, and strongly stimulates appetite, but no randomized trial of repeated therapeutic use exists and it has never been approved anywhere. FDA placed it in 503B Category 2 (ingredients flagged for significant safety risks in outsourcing facility compounding) in September 2023, it has no 503A listing (the pathway for pharmacies compounding for individual patients), and it is prohibited by WADA.", "mechanism": "GHRP-6 binds and activates the growth hormone secretagogue receptor (GHS-R1a) on pituitary somatotrophs and in the hypothalamus, producing a GH pulse that is synergistic with GHRH. As a ghrelin mimetic it also drives hunger, and it stimulates ACTH, cortisol, and prolactin release. It is the reference compound from which GHRP-2, hexarelin, and ipamorelin were derived.", "evidence_grade": "human_observational", "evidence_summary": "Human evidence is limited to acute dosing studies in healthy volunteers and children. Oral and intravenous doses release GH, and a placebo controlled sleep laboratory study found repeated intravenous boluses raised GH, ACTH, and cortisol and increased stage 2 sleep. No trial has measured body composition, strength, or clinical outcomes with chronic use.", "human_evidence": "Frieboes 1995 gave healthy men 4 intravenous boluses of 50 ug GHRP-6 overnight in a placebo controlled design and found increased GH, ACTH, and cortisol secretion and more stage 2 sleep. Bellone 1995 showed an oral dose (300 ug/kg) released GH in children with short stature, though less than intravenous administration. Camanni 1998 reviews the human pharmacology and notes the consistent rise in cortisol and prolactin. There are no controlled trials of chronic administration and no outcome data.", "animal_evidence": "Bowers 1984 described GHRP-6 as a synthetic hexapeptide that specifically released GH from rat pituitary cells in vitro and in vivo, with activity across species. Rodent studies established synergy with GHRH and appetite stimulation. Some rodent work suggests cardioprotective effects shared with hexarelin, but these have not been tested in humans.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Acute study doses only: 1 ug/kg intravenous bolus in adults, 4 x 50 ug intravenous overnight in the sleep study (Frieboes 1995), and 300 ug/kg orally in children (Bellone 1995). No chronic therapeutic dose has been established in human literature; subcutaneous regimens sold online are not from any published trial.", "routes": [ "Intravenous bolus (research studies)", "Oral (one pediatric study)", "Subcutaneous injection (as sold, not from published trials)" ], "side_effects": [ "Marked increase in hunger (the most consistently reported effect)", "Rise in cortisol, ACTH, and prolactin with each dose", "Reduced insulin sensitivity and higher blood glucose (cited in FDA's Category 2 rationale)", "Flushing, warmth, and sweating after intravenous doses", "Water retention and tingling reported with GH secretagogues generally", "No long term human safety data" ], "interactions": [ "Insulin and oral diabetes medications: GH secretagogues raise blood glucose", "Glucocorticoids: additive cortisol exposure because GHRP-6 raises ACTH", "GHRH analogs (sermorelin, CJC-1295): synergistic GH release, untested long term", "No formal human drug interaction studies exist" ], "contraindications": [ "Active cancer (theoretical GH and IGF-1 driven tumor growth)", "Diabetes or impaired glucose tolerance without monitoring", "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved for any use. FDA added GHRP-6 to the 503B Category 2 list on September 29, 2023, citing immunogenicity risk from aggregation and impurities, effects on cortisol, and increased blood glucose from reduced insulin sensitivity. As of the FDA page current to April 22, 2026, GHRP-6 remains in 503B Category 2 and has no 503A nomination, so no licensed pharmacy has a lawful basis to compound it. It was not among the peptides withdrawn from Category 2 in April 2026.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product; FDA placed GHRP-6 in 503B Category 2 on September 29, 2023 and it has no 503A nomination or listing.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is GHRP-6 legal in the United States?", "a": "It is not FDA approved and cannot be lawfully compounded (custom-made by a pharmacy). FDA placed GHRP-6 in 503B Category 2 (substances with significant safety risks) on September 29, 2023, and it has never been nominated for the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), so no licensed pharmacy can compound it. Possession is not a crime, but research chemical products are not lawful for human use and are untested for purity.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Does GHRP-6 work for muscle growth or fat loss?", "a": "It has not been tested for either. Published human studies measured hormone levels after single doses: GHRP-6 releases GH, and it does so orally as well as intravenously. No trial has measured muscle, fat, or strength with repeated dosing. Because it also raises cortisol and strongly increases appetite, a net body composition benefit cannot be assumed from GH physiology alone.", "source_ids": [ "frieboes-1995", "bellone-1995", "camanni-1998" ] }, { "q": "What are the side effects of GHRP-6?", "a": "Hunger is the hallmark: GHRP-6 is a ghrelin mimetic and is widely reported to cause intense appetite within minutes of injection. Controlled dosing studies show rises in cortisol, ACTH, and prolactin alongside GH. FDA's Category 2 rationale cites reduced insulin sensitivity and increased blood glucose. There are no long term safety data in humans.", "source_ids": [ "frieboes-1995", "fda-category-2" ] }, { "q": "How is GHRP-6 taken?", "a": "In published studies it was given as intravenous boluses (for example 50 ug repeated overnight, or 1 ug/kg) and orally at 300 ug/kg in children. Products sold online are subcutaneous injection vials taken one to three times daily, a schedule that has never been studied in a published trial.", "source_ids": [ "frieboes-1995", "bellone-1995" ] }, { "q": "How much does GHRP-6 cost?", "a": "There is no licensed US price because no pharmacy can lawfully compound it. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is GHRP-6 banned by WADA?", "a": "Yes. Growth hormone secretagogues and growth hormone releasing peptides, including GHRP-6, are prohibited at all times under section S2 of the WADA Prohibited List.", "source_ids": [ "wada-list" ] }, { "q": "GHRP-6 vs ipamorelin: which is better?", "a": "Ipamorelin was designed from the GHRP series to release GH with less effect on cortisol, ACTH, and prolactin, and it causes less hunger, so it is usually described as the more selective compound. GHRP-6 releases GH robustly but raises cortisol and appetite. Neither has long term human outcome data, both were placed in FDA 503B Category 2 in September 2023, and both are WADA prohibited.", "source_ids": [ "camanni-1998", "fda-category-2" ] }, { "q": "Does GHRP-6 work orally?", "a": "Partly. A 1995 study in children with short stature found that 300 ug/kg of GHRP-6 given orally released GH, though the response was smaller than with intravenous dosing. Oral bioavailability is low, which is why later development focused on non peptide oral secretagogues such as MK-677.", "source_ids": [ "bellone-1995", "bowers-1984" ] } ], "studies": [ { "pmid": "6714155", "title": "On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone", "year": 1984, "design": "In vitro pituitary cell and in vivo rat pharmacology", "population": "Rat pituitary cells and live rats", "outcome": "GHRP-6 specifically released GH in vitro and in vivo, defining the GHRP class", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/6714155/" }, { "pmid": "7617137", "title": "Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man", "year": 1995, "design": "Placebo controlled sleep laboratory study", "population": "Healthy young men", "outcome": "Four overnight 50 ug intravenous boluses increased GH, ACTH, and cortisol secretion and stage 2 sleep", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/7617137/" }, { "pmid": "7581965", "title": "Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature", "year": 1995, "design": "Pharmacology study", "population": "Children with short stature", "outcome": "Oral GHRP-6 at 300 ug/kg released GH, with a smaller response than intravenous dosing", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/7581965/" }, { "pmid": "9465289", "title": "Growth hormone-releasing peptides and their analogs", "year": 1998, "design": "Narrative review", "population": "Human and animal pharmacology of GHRP-6, GHRP-2, hexarelin, and analogs", "outcome": "Summarizes GH releasing potency, synergy with GHRH, and effects on cortisol and prolactin", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9465289/" } ], "sources": [ { "id": "bowers-1984", "type": "pubmed", "title": "Bowers CY et al. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 1984", "url": "https://pubmed.ncbi.nlm.nih.gov/6714155/", "pmid": "6714155", "year": 1984 }, { "id": "frieboes-1995", "type": "pubmed", "title": "Frieboes RM et al. Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology 1995", "url": "https://pubmed.ncbi.nlm.nih.gov/7617137/", "pmid": "7617137", "year": 1995 }, { "id": "bellone-1995", "type": "pubmed", "title": "Bellone J et al. Growth hormone-releasing effect of oral GHRP-6 administration in children with short stature. Eur J Endocrinol 1995", "url": "https://pubmed.ncbi.nlm.nih.gov/7581965/", "pmid": "7581965", "year": 1995 }, { "id": "camanni-1998", "type": "pubmed", "title": "Camanni F, Ghigo E, Arvat E. Growth hormone-releasing peptides and their analogs. Front Neuroendocrinol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9465289/", "pmid": "9465289", "year": 1998 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ghrp-2", "ipamorelin", "hexarelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "hexarelin", "name": "Hexarelin", "aliases": [ "Examorelin", "EP 23905", "His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2", "Hexarelin acetate" ], "class": "Synthetic hexapeptide growth hormone secretagogue (ghrelin receptor agonist), methylated analog of GHRP-6", "one_liner": "Potent lab-made growth hormone releaser with 1990s human data; the GH response fades with repeated use; never approved anywhere; WADA prohibited.", "summary": "Hexarelin (examorelin) is a synthetic six amino acid analog (modified version) of GHRP-6 that releases growth hormone through the ghrelin receptor (the receptor for the body's hunger hormone) and is active by intravenous, subcutaneous (under the skin), intranasal, and even oral routes. Human studies in the 1990s showed strong acute GH release, but a 16 week study found the GH response declined substantially with continued use, and development stopped without any approval. It is not on any FDA compounding list (the lists of raw ingredients pharmacies may use), is not FDA approved, and is prohibited by WADA.", "mechanism": "Hexarelin activates the growth hormone secretagogue receptor (GHS-R1a) on pituitary somatotrophs and hypothalamic neurons, releasing GH synergistically with GHRH and raising prolactin, ACTH, and cortisol. It also binds CD36 on cardiac and vascular cells, which is the basis of animal studies showing cardioprotection independent of GH. Methylation of the tryptophan residue makes it more stable than GHRP-6.", "evidence_grade": "human_observational", "evidence_summary": "Human data are acute and short term pharmacology studies from the 1990s. A 1994 dose finding study showed GH release after intravenous (1 to 2 ug/kg), subcutaneous, intranasal, and oral dosing in healthy adults. Studies in GH deficient and short children confirmed GH release when pituitary function was intact. A 16 week trial of twice daily subcutaneous hexarelin in healthy adults found the GH response attenuated by about half and IGF-1 did not rise durably. A small surgical study found a single intravenous dose improved cardiac indices during bypass. No randomized trial of clinical outcomes exists.", "human_evidence": "Ghigo 1994: hexarelin released GH in healthy volunteers by intravenous, subcutaneous, intranasal, and oral routes, with intravenous 1 to 2 ug/kg producing the largest response. Loche 1995: GH release in short normal and obese children and reduced response in hypopituitary subjects. Arvat 1997: hexarelin and GHRP-2 released more GH than GHRH and raised prolactin, ACTH, and cortisol. Rahim 1998: 16 weeks of 1.5 mg twice daily subcutaneous hexarelin in healthy adults led to a partial loss of the GH response and no sustained IGF-1 rise, with recovery after washout. Frieboes 2004: hexarelin decreased slow wave sleep and raised GH, ACTH, cortisol, and prolactin during sleep. Broglio 2002: a single 2 ug/kg intravenous dose improved cardiac performance indices in patients with coronary artery disease during bypass surgery.", "animal_evidence": "Rodent studies show hexarelin protects the heart against ischemia and reperfusion injury and improves cardiac function after infarction, partly through CD36 binding rather than GH. Rat studies also show GH release and synergy with GHRH. These cardiac findings have not progressed to human outcome trials.", "conditions": [ "growth-hormone-deficiency" ], "literature_dosing": "Acute studies used 1 to 2 ug/kg intravenously, 2 to 3 ug/kg subcutaneously, 20 ug/kg intranasally, and up to 20 mg orally in adults (Ghigo 1994). The only chronic study used 1.5 mg subcutaneously twice daily for 16 weeks (Rahim 1998). No dose has been established for any therapeutic use.", "routes": [ "Intravenous (research studies)", "Subcutaneous injection (research studies and as sold)", "Intranasal and oral (research studies, lower bioavailability)" ], "side_effects": [ "Rise in cortisol, ACTH, and prolactin with each dose", "Loss of GH response with continued use (about 50% attenuation over 16 weeks)", "Transient flushing and warmth after intravenous dosing", "Reduced slow wave sleep in a controlled sleep study", "Increased hunger (ghrelin mimetic effect)", "No long term human safety data" ], "interactions": [ "Insulin and oral diabetes medications: GH secretagogues raise blood glucose", "Glucocorticoids: additive cortisol exposure", "GHRH analogs (sermorelin, CJC-1295): synergistic GH release, untested long term", "No formal human drug interaction studies exist" ], "contraindications": [ "Active cancer (theoretical GH and IGF-1 driven tumor growth)", "Diabetes or impaired glucose tolerance without monitoring", "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Not FDA approved and never commercially developed to approval anywhere. Hexarelin does not appear on the FDA 503A or 503B bulks lists or in Category 2 as of the FDA pages current to April 2026, which means it has not been nominated and there is no lawful basis for a compounding pharmacy to use it. It was not part of the April 2026 Category 2 withdrawals or the July 2026 advisory committee review.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product, not nominated for the 503A bulks list, and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is hexarelin legal in the United States?", "a": "It is not FDA approved and is not on any FDA compounding list (the lists of raw ingredients pharmacies may use to custom-make drugs), so no licensed pharmacy can lawfully compound it. It has never been approved in any country. Possession is not a crime, but research chemical products are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Does hexarelin work to raise growth hormone?", "a": "Acutely, yes, and strongly: intravenous 1 to 2 ug/kg produced larger GH peaks than GHRH in healthy adults, and it worked by subcutaneous, intranasal, and oral routes. The catch is tolerance. In the only 16 week study, the GH response to twice daily injections fell by about half and IGF-1 did not stay elevated, which is one reason development stopped.", "source_ids": [ "ghigo-1994", "arvat-1997", "rahim-1998" ] }, { "q": "What are the side effects of hexarelin?", "a": "Each dose raises cortisol, ACTH, and prolactin along with GH, and a controlled sleep study found it reduced slow wave sleep. Flushing after intravenous dosing and hunger are reported. The GH response fades with continued use. No long term human safety data exist.", "source_ids": [ "arvat-1997", "frieboes-2004", "rahim-1998" ] }, { "q": "How is hexarelin taken?", "a": "In published studies it was given intravenously (1 to 2 ug/kg), subcutaneously (2 to 3 ug/kg, or 1.5 mg twice daily in the chronic study), intranasally, and orally at high doses. Products sold online are subcutaneous injection vials. No therapeutic dosing schedule has been established.", "source_ids": [ "ghigo-1994", "rahim-1998" ] }, { "q": "How much does hexarelin cost?", "a": "There is no licensed US price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is hexarelin banned by WADA?", "a": "Yes. Growth hormone secretagogues including hexarelin (examorelin) are prohibited at all times under section S2 of the WADA Prohibited List.", "source_ids": [ "wada-list" ] }, { "q": "Hexarelin vs GHRP-6: what is the difference?", "a": "Hexarelin is GHRP-6 with a methylated tryptophan, which makes it more stable and, in head to head human studies, a somewhat more potent GH releaser. Both raise cortisol and prolactin and both stimulate hunger. GHRP-6 was placed in FDA 503B Category 2 in September 2023 while hexarelin has never been nominated at all. Neither has long term outcome data.", "source_ids": [ "camanni-1998", "fda-category-2" ] }, { "q": "Does hexarelin protect the heart?", "a": "In rodents, hexarelin reduces ischemia and reperfusion injury through CD36 binding independent of GH. In humans the only data are a small study in which a single 2 ug/kg intravenous dose improved cardiac performance indices during coronary bypass surgery. No trial has tested repeated dosing for any cardiac condition, so the cardioprotection claim is animal level evidence.", "source_ids": [ "broglio-2002" ] } ], "studies": [ { "pmid": "8126144", "title": "Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man", "year": 1994, "design": "Dose finding pharmacology study", "population": "Healthy adult volunteers", "outcome": "GH release by all four routes; intravenous 1 to 2 ug/kg produced the largest response", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/8126144/" }, { "pmid": "9589671", "title": "Growth hormone status during long-term hexarelin therapy", "year": 1998, "design": "16 week open treatment study with washout", "population": "Healthy adults given 1.5 mg subcutaneously twice daily", "outcome": "GH response to hexarelin attenuated by about half over 16 weeks with no sustained IGF-1 rise; recovered after washout", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9589671/" }, { "pmid": "9285939", "title": "Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man", "year": 1997, "design": "Crossover pharmacology study", "population": "Healthy young adults", "outcome": "Hexarelin released more GH than GHRH and raised prolactin, ACTH, and cortisol", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9285939/" }, { "pmid": "15177700", "title": "Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers", "year": 2004, "design": "Placebo controlled sleep laboratory study", "population": "Healthy volunteers", "outcome": "Reduced slow wave sleep; increased GH, ACTH, cortisol, and prolactin", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/15177700/" }, { "pmid": "12144941", "title": "Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery", "year": 2002, "design": "Small acute intervention study", "population": "Patients with coronary artery disease undergoing bypass surgery", "outcome": "A single 2 ug/kg intravenous dose improved cardiac performance indices", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/12144941/" }, { "pmid": "7673411", "title": "The effect of hexarelin on growth hormone (GH) secretion in patients with GH deficiency", "year": 1995, "design": "Pharmacology study", "population": "Children and adults with GH deficiency", "outcome": "GH response present when pituitary function was intact and blunted in organic hypopituitarism", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/7673411/" } ], "sources": [ { "id": "ghigo-1994", "type": "pubmed", "title": "Ghigo E et al. Growth hormone-releasing activity of hexarelin after intravenous, subcutaneous, intranasal, and oral administration in man. J Clin Endocrinol Metab 1994", "url": "https://pubmed.ncbi.nlm.nih.gov/8126144/", "pmid": "8126144", "year": 1994 }, { "id": "rahim-1998", "type": "pubmed", "title": "Rahim A, O'Neill PA, Shalet SM. Growth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9589671/", "pmid": "9589671", "year": 1998 }, { "id": "arvat-1997", "type": "pubmed", "title": "Arvat E et al. Effects of GHRP-2 and hexarelin on GH, prolactin, ACTH and cortisol levels in man. Peptides 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/9285939/", "pmid": "9285939", "year": 1997 }, { "id": "frieboes-2004", "type": "pubmed", "title": "Frieboes RM et al. Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Psychoneuroendocrinology 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15177700/", "pmid": "15177700", "year": 2004 }, { "id": "broglio-2002", "type": "pubmed", "title": "Broglio F et al. Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. Eur J Pharmacol 2002", "url": "https://pubmed.ncbi.nlm.nih.gov/12144941/", "pmid": "12144941", "year": 2002 }, { "id": "camanni-1998", "type": "pubmed", "title": "Camanni F, Ghigo E, Arvat E. Growth hormone-releasing peptides and their analogs. Front Neuroendocrinol 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9465289/", "pmid": "9465289", "year": 1998 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ghrp-6", "ghrp-2", "ipamorelin", "mk-677" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "mk-677", "name": "MK-677 (ibutamoren)", "aliases": [ "Ibutamoren", "Ibutamoren mesylate", "MK-0677", "L-163,191", "Nutrobal" ], "class": "Oral non peptide growth hormone secretagogue (small molecule ghrelin receptor agonist)", "one_liner": "Oral ghrelin mimetic with real RCTs: raises IGF-1 and lean mass modestly, raises glucose and appetite, a heart failure signal stopped development. Not approved.", "summary": "MK-677 (ibutamoren) is not a peptide but an oral small molecule that activates the ghrelin receptor and raises growth hormone and IGF-1 for a full day after a single dose. It has more randomized trial data than any injectable GH secretagogue: two years of 25 mg daily in healthy older adults increased fat free mass by about 1.1 kg versus placebo but also raised fasting glucose and appetite, and a hip fracture trial was stopped early for a congestive heart failure signal. It has never been approved, FDA placed it in both 503A and 503B Category 2, and it is prohibited by WADA.", "mechanism": "Ibutamoren is an orally active, long acting agonist of the growth hormone secretagogue receptor (GHS-R1a), the ghrelin receptor. It amplifies pulsatile GH release from the pituitary without changing GH pulse frequency, which raises IGF-1 into the young adult range in older people. As a ghrelin mimetic it increases hunger, and the GH rise reduces insulin sensitivity. Its half life supports once daily dosing.", "evidence_grade": "human_rct", "evidence_summary": "Several randomized placebo controlled trials, mostly from the 1990s and 2000s. Nass 2008 (n = 65 healthy adults aged 60 to 81, 2 years): 25 mg daily increased fat free mass by about 1.1 kg and IGF-1 by roughly 50 to 60% versus placebo, without improving strength or function, while fasting glucose and insulin resistance increased. Svensson 1998 (n = 24 obese men, 8 weeks): fat free mass rose about 3 kg and energy expenditure increased, with no loss of fat. Murphy 1999: bone turnover markers rose in elderly adults. Sevigny 2008 (n = 563 Alzheimer patients, 12 months): no effect on disease progression. Adunsky 2011: a phase 2b hip fracture trial was terminated early for a potential congestive heart failure signal.", "human_evidence": "Chapman 1996 (healthy elderly, 4 weeks) showed 25 mg daily raised 24 hour GH and IGF-1 into the young adult range. Svensson 1998 (24 obese men, 8 weeks) found 25 mg daily raised GH and IGF-1, increased fat free mass by about 3 kg and basal metabolic rate, with no significant change in fat mass. Murphy 1999 found increased markers of bone formation and resorption in older adults. Nass 2008 (65 adults, 2 years) found 25 mg daily increased fat free mass by about 1.1 kg and appendicular lean mass versus placebo, increased fasting glucose by about 0.3 mmol/L, reduced insulin sensitivity, and caused more edema, appetite increase, and muscle pain, with no improvement in strength or function. Sevigny 2008 (563 patients with Alzheimer disease, 12 months) found no clinical benefit. Adunsky 2011 (hip fracture recovery) was stopped early due to a possible heart failure signal, which is the basis of FDA's Category 2 rationale.", "animal_evidence": "Ibutamoren was developed from earlier non peptide secretagogues in dog and rat models, where it produced sustained GH release and IGF-1 elevation with oral dosing. Animal data are pharmacological; the clinically relevant evidence is human.", "conditions": [ "growth-hormone-deficiency", "muscle-wasting" ], "literature_dosing": "Randomized trials used 25 mg orally once daily (Chapman 1996, Svensson 1998, Nass 2008, Sevigny 2008), with 2 mg and 50 mg arms in early studies. These are research doses from trials that did not lead to approval, not a therapeutic recommendation.", "routes": [ "Oral capsule or tablet, once daily (all trials and as sold)" ], "side_effects": [ "Increased appetite (the most common effect across trials)", "Higher fasting glucose and reduced insulin sensitivity (about 0.3 mmol/L glucose rise over 2 years in Nass 2008)", "Edema and fluid retention", "Muscle and joint pain", "Congestive heart failure signal that halted a hip fracture trial (FDA Category 2 rationale)", "Transient rise in cortisol and prolactin", "Lethargy, numbness, and tingling reported anecdotally", "No strength or functional benefit shown despite lean mass gain" ], "interactions": [ "Insulin and oral diabetes medications: raises blood glucose and can worsen control", "Diuretics and heart failure medications: fluid retention and the heart failure signal are relevant", "GHRH analogs and injectable GH secretagogues: additive GH exposure, untested", "No formal human drug interaction studies published" ], "contraindications": [ "Heart failure or reduced ejection fraction (trial terminated for heart failure signal)", "Diabetes or prediabetes without close monitoring", "Active cancer (IGF-1 elevation is a theoretical tumor growth concern)", "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S2)" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not FDA approved for any use. FDA placed ibutamoren mesylate in 503B Category 2 on December 29, 2022 and in 503A Category 2 on September 29, 2023, citing the potential for congestive heart failure based on the terminated hip fracture trial. As of the FDA page current to April 22, 2026, it remains in both categories, so no licensed pharmacy or outsourcing facility can lawfully compound it. It was not among the substances withdrawn from Category 2 in April 2026. It is widely sold online as a research chemical or mislabeled supplement.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product; FDA placed ibutamoren in both 503A and 503B Category 2, and it may not lawfully be sold as a dietary supplement.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "What is MK-677?", "a": "MK-677, also called ibutamoren, is an oral small molecule, not a peptide, that activates the ghrelin receptor and makes the pituitary release growth hormone. Taken once a day in trials, it raised 24 hour growth hormone and IGF-1. It was studied for age related muscle loss, hip fracture recovery, and Alzheimer disease but never approved. FDA lists it in Category 2 for compounding because of a heart failure signal, and it is prohibited in sport.", "source_ids": [ "chapman-1996", "sevigny-2008", "adunsky-2011", "fda-category-2", "wada-list" ] }, { "q": "Is MK-677 legal in the United States?", "a": "It is not an approved drug and cannot lawfully be compounded or sold as a supplement. FDA placed ibutamoren in 503B Category 2 in December 2022 and 503A Category 2 in September 2023 because of a heart failure signal, and it remains there as of April 2026. Possession is not a crime, but products sold online are unapproved drugs.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Does MK-677 build muscle?", "a": "It adds a little lean mass, not strength. In a 2 year randomized trial of 65 healthy older adults, 25 mg daily increased fat free mass by about 1.1 kg versus placebo and raised IGF-1 substantially, but strength and physical function did not improve. An 8 week study in obese men found about 3 kg more fat free mass and higher energy expenditure with no fat loss. Some of the lean mass gain is water.", "source_ids": [ "nass-2008", "svensson-1998" ] }, { "q": "What are the side effects of MK-677?", "a": "Increased appetite, fluid retention and edema, muscle pain, and higher fasting glucose with reduced insulin sensitivity were seen in the 2 year trial. The most serious concern is cardiac: a randomized hip fracture trial was stopped early because of a potential congestive heart failure signal, and FDA cites that trial in its Category 2 rationale. Tingling, lethargy, and vivid dreams are reported anecdotally.", "source_ids": [ "nass-2008", "adunsky-2011", "fda-category-2" ] }, { "q": "Is MK-677 a pill or an injection?", "a": "A pill. Unlike the injectable growth hormone peptides, ibutamoren was taken by mouth once a day in its trials, and because it is long acting a single daily dose kept growth hormone and IGF-1 raised. Being oral does not make it lawful or safer: it is unapproved, in Category 2 for both compounding pathways, and raised glucose and appetite in trials.", "source_ids": [ "chapman-1996", "nass-2008", "fda-category-2" ] }, { "q": "How much does MK-677 cost?", "a": "There is no licensed price. FDA has treated products containing ibutamoren as unapproved drugs, and purity is not verified. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is MK-677 banned by WADA?", "a": "Yes. Ibutamoren is named explicitly under section S2 (growth hormone secretagogues) of the WADA Prohibited List and is prohibited at all times. It is orally active and detectable in urine, and several athletes have been sanctioned for it.", "source_ids": [ "wada-list" ] }, { "q": "MK-677 vs ipamorelin: which is better?", "a": "They act on the same ghrelin receptor. MK-677 is oral and long acting, with far more trial data, including the 2 year lean mass study and the heart failure signal. Ipamorelin is an injectable peptide with only small pharmacology studies and no outcome data. MK-677 raises glucose and appetite more because it stimulates the receptor all day. Both are in FDA Category 2 and both are WADA prohibited.", "source_ids": [ "nass-2008", "fda-category-2" ] }, { "q": "Does MK-677 help with sleep, bone density, or aging?", "a": "Evidence is thin. Bone turnover markers rose in older adults over 9 weeks in one trial, but fracture or bone density outcomes were not shown. The 2 year trial in older adults found no functional benefit. A 12 month trial in 563 people with Alzheimer disease found no effect on progression. Sleep effects come from small older studies and anecdote, not outcome trials.", "source_ids": [ "murphy-1999", "nass-2008", "sevigny-2008" ] } ], "studies": [ { "pmid": "18981485", "title": "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial", "year": 2008, "design": "Randomized, double blind, placebo controlled trial, 2 years", "n": 65, "population": "Healthy adults aged 60 to 81", "outcome": "25 mg daily increased fat free mass by about 1.1 kg and IGF-1 versus placebo; no strength or function benefit; fasting glucose and insulin resistance increased", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/" }, { "pmid": "9467542", "title": "Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure", "year": 1998, "design": "Randomized, double blind, placebo controlled trial, 8 weeks", "n": 24, "population": "Obese men", "outcome": "Fat free mass increased about 3 kg and basal metabolic rate rose; no significant fat loss", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9467542/" }, { "pmid": "8954023", "title": "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects", "year": 1996, "design": "Randomized, double blind, placebo controlled trial, 4 weeks", "population": "Healthy elderly adults", "outcome": "25 mg daily raised 24 hour GH secretion and IGF-1 into the young adult range", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/8954023/" }, { "pmid": "10404019", "title": "Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults", "year": 1999, "design": "Randomized, double blind, placebo controlled trial, 9 weeks", "population": "Healthy and functionally impaired elderly adults", "outcome": "Increased markers of bone formation and bone resorption", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/10404019/" }, { "pmid": "19015485", "title": "Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial", "year": 2008, "design": "Randomized, double blind, placebo controlled trial, 12 months", "n": 563, "population": "Adults with mild to moderate Alzheimer disease", "outcome": "No effect on cognitive or functional progression despite IGF-1 increase", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19015485/" }, { "pmid": "21067829", "title": "MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study", "year": 2011, "design": "Randomized, double blind, placebo controlled phase 2b trial, terminated early", "population": "Older adults recovering from hip fracture", "outcome": "Trial stopped early for a potential congestive heart failure safety signal; no functional benefit established", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/21067829/" } ], "sources": [ { "id": "nass-2008", "type": "pubmed", "title": "Nass R et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18981485/", "pmid": "18981485", "year": 2008 }, { "id": "svensson-1998", "type": "pubmed", "title": "Svensson J et al. Two-month treatment of obese subjects with the oral GH secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9467542/", "pmid": "9467542", "year": 1998 }, { "id": "chapman-1996", "type": "pubmed", "title": "Chapman IM et al. Stimulation of the GH-IGF-I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab 1996", "url": "https://pubmed.ncbi.nlm.nih.gov/8954023/", "pmid": "8954023", "year": 1996 }, { "id": "murphy-1999", "type": "pubmed", "title": "Murphy MG et al. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. J Bone Miner Res 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10404019/", "pmid": "10404019", "year": 1999 }, { "id": "sevigny-2008", "type": "pubmed", "title": "Sevigny JJ et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/19015485/", "pmid": "19015485", "year": 2008 }, { "id": "adunsky-2011", "type": "pubmed", "title": "Adunsky A et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21067829/", "pmid": "21067829", "year": 2011 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics (ibutamoren named)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ipamorelin", "ghrp-2", "ghrp-6", "sermorelin" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "MK-677 (ibutamoren): evidence, side effects, legality", "description": "MK-677 (ibutamoren) is an oral ghrelin mimetic, not a peptide: what its trials showed, side effects, the heart failure signal, and US legality.", "h1": "MK-677 (ibutamoren)", "headings": { "safety": "MK-677 side effects" } } }, { "slug": "aod-9604", "name": "AOD-9604", "aliases": [ "AOD9604", "Anti-obesity drug 9604", "hGH fragment 177-191 (tyrosine modified)", "Tyr-hGH 177-191", "AOD-9604 acetate", "AOD 9604", "AOD-9604 peptide" ], "class": "Synthetic 16 amino acid C terminal fragment of human growth hormone (residues 177 to 191 with an N terminal tyrosine)", "one_liner": "Growth hormone fragment that raised fat burning in obese mice; no human trial in PubMed shows weight loss; FDA nomination withdrawn; banned by WADA.", "summary": "AOD-9604 is a synthetic peptide copying the tail end (residues 177 to 191) of human growth hormone, intended to keep the fat burning activity of growth hormone without its effects on growth and blood sugar. In obese mice it increased fat burning and reduced weight gain without raising IGF-1 (a growth factor made in response to growth hormone) or glucose, but no human trial indexed in PubMed demonstrates weight loss and the sponsor's obesity program ended in the mid 2000s. FDA placed it in 503A Category 2 (compounding ingredients FDA flagged for significant safety risks) in 2023; the nomination was later withdrawn, so it is no longer in Category 2 but has no lawful way to be compounded (custom-made by a pharmacy), and it is prohibited by WADA (the World Anti-Doping Agency).", "mechanism": "The 177 to 191 region of growth hormone is proposed to stimulate lipolysis and inhibit lipogenesis in adipose tissue, possibly through beta-3 adrenergic receptor dependent pathways, without binding the GH receptor in the way full length GH does. In mice it did not raise IGF-1, glucose, or insulin. Whether this mechanism operates in humans at the doses used has not been shown.", "evidence_grade": "animal_only", "evidence_summary": "Rodent studies from one Australian group around 2000 to 2001 showed AOD-9604 increased fat oxidation, reduced body weight gain, and lowered fat mass in obese mice, with the effect absent in beta-3 adrenergic receptor knockout mice. The sponsor ran randomized human obesity trials in the early 2000s, but no indexed publication reports a meaningful weight loss benefit and the program was discontinued. PeptideAgent therefore grades the evidence animal-only; the human trials that exist did not produce a positive published result.", "human_evidence": "No indexed human randomized trial reporting weight loss identified. The sponsor's phase 2 obesity trials in the early 2000s were not published in an indexed journal and the program was discontinued, which is consistent with a lack of efficacy. FDA's Category 2 rationale states it identified only limited safety information and serious adverse events with unclear causality. Newer uses promoted online (joint and cartilage repair) have no published human data.", "animal_evidence": "Ng 2000: metabolic studies in rodents showed the synthetic lipolytic domain increased lipolysis and inhibited lipogenesis without the diabetogenic effects of GH. Heffernan 2001 (Endocrinology): chronic treatment in obese mice reduced weight gain and fat mass, with the effect lost in beta-3 adrenergic receptor knockout mice. Heffernan 2001 (Int J Obes): chronic treatment of obese mice with hGH or the modified C terminal fragment increased fat oxidation and produced weight loss. Doses in mice were on the order of 250 ug/kg to 2 mg/kg per day.", "conditions": [ "obesity" ], "literature_dosing": "Not established in human literature. Mouse studies used roughly 250 ug/kg to 2 mg/kg per day orally or by injection; these rodent ranges do not translate to a human dose, and the unpublished human trials do not provide a citable regimen.", "routes": [ "Subcutaneous injection (as sold)", "Oral and injectable (mouse studies)", "Topical and intra-articular (promoted online, no published data)" ], "side_effects": [ "No systematic human safety data published", "FDA cites serious adverse events possibly associated with AOD-9604 with unclear causality", "Injection site reactions reported anecdotally", "Headache and nausea reported anecdotally", "Immunogenicity risk from aggregation and impurities (FDA Category 2 rationale)" ], "interactions": [ "No formal human interaction studies exist", "In mice it did not change glucose or IGF-1, so interactions with diabetes medications are theoretical rather than observed" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S2)", "Any use requiring an approved product: none exists" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Not FDA approved. FDA placed AOD-9604 in 503A Category 2 in 2023, citing immunogenicity risk, limited safety information, and serious adverse events with unclear causality. FDA's Category 2 page (current as of April 22, 2026) now lists AOD-9604 under bulk drug substances nominated but withdrawn, meaning the nominator withdrew it and it is no longer in Category 2. Because it has no active nomination and is not on the 503A bulks list, there is still no lawful basis for a compounding pharmacy to use it. It was not among the six peptides reviewed by the advisory committee in July 2026.", "typical_cost": "Not available through licensed US channels since the 2023 Category 2 placement. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date; the 503A nomination was withdrawn and it is not on the bulks list.", "Not available as an FDA approved product; a 503A pharmacy has no listed basis to compound it.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "What is AOD-9604?", "a": "AOD-9604 is a synthetic copy of the tail end of human growth hormone (residues 177 to 191, with an added tyrosine), designed to keep growth hormone's fat burning effect without its growth promoting effects. In obese mice it increased fat burning (fat oxidation) and reduced weight gain. It is not FDA approved, it is off the FDA Category 2 list (compounding ingredients flagged for significant safety risks) only because its nomination was withdrawn, and it has no lawful compounded source.", "source_ids": [ "ng-2000", "heffernan-2001-ijo", "fda-category-2" ] }, { "q": "Is AOD-9604 legal in the United States?", "a": "It is not FDA approved and cannot lawfully be compounded. FDA placed it in 503A Category 2 in 2023, and although the nomination has since been withdrawn (so it is no longer listed in Category 2 as of April 2026), it has no place on the 503A bulks list, which leaves compounding pharmacies without a lawful basis to make it. Possession is not a crime; research chemical products are not for human use.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Does AOD-9604 work for weight loss?", "a": "In obese mice, yes: it increased fat oxidation and reduced fat mass without raising blood sugar or IGF-1. In humans, no published trial shows it works. The sponsor ran randomized obesity trials in the early 2000s and discontinued the program without publishing a positive result. PeptideAgent grades the evidence animal-only.", "source_ids": [ "heffernan-2001-endo", "heffernan-2001-ijo", "ng-2000" ] }, { "q": "What are the side effects of AOD-9604?", "a": "There is no systematic human safety data in the indexed literature. FDA's Category 2 rationale notes it identified serious adverse events that may be associated with AOD-9604, though causality is not clear, and flags immunogenicity risk from peptide impurities. Injection site reactions, headache, and nausea are reported anecdotally.", "source_ids": [ "fda-category-2" ] }, { "q": "How is AOD-9604 taken?", "a": "Products sold to people are subcutaneous injection vials, and some clinics have promoted oral, topical, and joint injection use. None of these routes has a published human dose, and mouse study doses do not translate to a human regimen. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "heffernan-2001-endo", "ng-2000" ] }, { "q": "How much does AOD-9604 cost?", "a": "It is no longer available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is AOD-9604 banned by WADA?", "a": "Yes. The WADA Prohibited List names growth hormone fragments, including AOD-9604 and hGH 176-191, under section S2, prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "AOD-9604 vs semaglutide for fat loss: how do they compare?", "a": "They are not comparable in evidence. Semaglutide has large randomized trials showing about 15% average weight loss over 68 weeks and is FDA approved. AOD-9604 has mouse data and no published human trial showing weight loss, and it is not available through licensed channels. Anyone offered AOD-9604 for weight loss is being offered an unproven product in place of proven ones.", "source_ids": [ "heffernan-2001-endo", "fda-category-2" ] }, { "q": "Does AOD-9604 help joints or cartilage?", "a": "There is no published human evidence for joint repair. The claim comes from marketing and from a small amount of animal work on osteoarthritis models. No randomized trial in people with joint pain or cartilage injury has been published.", "source_ids": [ "fda-category-2" ] } ], "studies": [ { "pmid": "11146367", "title": "Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone", "year": 2000, "design": "Rodent metabolic pharmacology", "population": "Rats and mice", "outcome": "The synthetic 177 to 191 fragment stimulated lipolysis and inhibited lipogenesis without GH like effects on glucose or IGF-1", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/11146367/" }, { "pmid": "11713213", "title": "The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice", "year": 2001, "design": "Chronic treatment study in obese and knockout mice", "population": "Obese mice and beta-3 adrenergic receptor knockout mice", "outcome": "Reduced weight gain and fat mass in obese mice; effect absent in beta-3 receptor knockouts", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/11713213/" }, { "pmid": "11673763", "title": "Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment", "year": 2001, "design": "Chronic treatment study in obese mice", "population": "Obese mice", "outcome": "Increased fat oxidation and weight loss with the modified C terminal fragment", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/11673763/" } ], "sources": [ { "id": "ng-2000", "type": "pubmed", "title": "Ng FM et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res 2000", "url": "https://pubmed.ncbi.nlm.nih.gov/11146367/", "pmid": "11146367", "year": 2000 }, { "id": "heffernan-2001-endo", "type": "pubmed", "title": "Heffernan M et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11713213/", "pmid": "11713213", "year": 2001 }, { "id": "heffernan-2001-ijo", "type": "pubmed", "title": "Heffernan MA et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11673763/", "pmid": "11673763", "year": 2001 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list and withdrawn nominations, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone fragments, e.g. AOD-9604 and hGH 176-191)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "semaglutide", "tesofensine", "5-amino-1mq", "tesamorelin" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "AOD-9604 peptide: evidence, side effects, legal status", "description": "What AOD-9604 peptide is (a modified growth hormone fragment), what the mouse fat loss studies show, side effects, and its 2026 legal status.", "h1": "AOD-9604 peptide", "headings": { "evidence": "AOD-9604 benefits: what the evidence shows", "safety": "AOD-9604 side effects" } } }, { "slug": "tesofensine", "name": "Tesofensine", "aliases": [ "NS 2330", "NS-2330", "Tesofensine citrate" ], "class": "Oral small molecule triple monoamine (serotonin, noradrenaline, dopamine) reuptake inhibitor; not a peptide", "one_liner": "Not a peptide: an oral triple reuptake inhibitor that produced about 10% placebo adjusted weight loss over 24 weeks in a phase 2 RCT. Not FDA approved.", "summary": "Tesofensine is an oral small molecule, not a peptide, that blocks reuptake of serotonin, noradrenaline, and dopamine and was first studied for Parkinson and Alzheimer disease before weight loss was noticed. In a 24 week randomized trial of 203 obese adults, 0.5 mg daily produced 9.2% and 1.0 mg 10.6% placebo adjusted weight loss, with dose related increases in heart rate and blood pressure. It has not been approved by FDA and appears on peptide sellers' lists only because it is marketed alongside them.", "mechanism": "Tesofensine inhibits the presynaptic transporters for serotonin, noradrenaline, and dopamine, raising synaptic levels of all three. The appetite suppression is attributed mainly to noradrenergic and dopaminergic effects on hypothalamic feeding circuits, with a smaller contribution from increased energy expenditure. It has an active metabolite and a long half life of several days.", "evidence_grade": "human_rct", "evidence_summary": "One well conducted phase 2 randomized controlled trial in obesity (Astrup 2008, n = 203, 24 weeks) showed mean weight loss of 6.7 kg (0.25 mg), 11.3 kg (0.5 mg), and 12.8 kg (1.0 mg) versus 2.2 kg with placebo and diet, equal to placebo adjusted losses of 4.5%, 9.2%, and 10.6%. Dry mouth, nausea, constipation, insomnia, and a heart rate increase of about 7 beats per minute at the top dose were seen, with blood pressure rises at 1.0 mg. No completed US phase 3 program has been published in the indexed literature.", "human_evidence": "Astrup 2008 (Lancet): 203 obese adults (BMI 30 to 40) randomized to placebo or tesofensine 0.25, 0.5, or 1.0 mg daily with a hypocaloric diet for 24 weeks. Weight loss was 2.2 kg, 6.7 kg, 11.3 kg, and 12.8 kg respectively; the 0.5 mg dose achieved most of the benefit with fewer cardiovascular effects. Adverse events were dry mouth, nausea, constipation, hard stools, diarrhea, and insomnia; heart rate rose by 7.4 beats per minute at 1.0 mg and blood pressure increased at that dose. Earlier trials in Parkinson and Alzheimer disease found no meaningful benefit for those conditions but recorded weight loss as a side effect. Doggrell 2009 reviews the trial and the cardiovascular concerns that shaped later development.", "animal_evidence": "Rodent studies showed reduced food intake and body weight through monoamine reuptake inhibition, consistent with the human findings. Animal data are supportive rather than the primary evidence base.", "conditions": [ "obesity" ], "literature_dosing": "Phase 2 trial doses: 0.25 mg, 0.5 mg, or 1.0 mg orally once daily for 24 weeks (Astrup 2008). The 0.5 mg dose was identified as the best balance of efficacy and tolerability. These are trial doses for an unapproved drug, not a recommendation.", "routes": [ "Oral tablet or capsule, once daily" ], "side_effects": [ "Dry mouth (most common)", "Nausea, constipation, and hard stools", "Insomnia and mood changes", "Increased heart rate (about 7 beats per minute at 1.0 mg)", "Increased blood pressure at the 1.0 mg dose", "Dizziness and headache", "Long term cardiovascular safety not established" ], "interactions": [ "Monoamine oxidase inhibitors and serotonergic antidepressants: theoretical risk of serotonin syndrome and hypertensive effects", "Stimulants and sympathomimetics: additive heart rate and blood pressure effects", "Antihypertensives: may need adjustment because of pressor effects", "No formal human drug interaction studies published" ], "contraindications": [ "Uncontrolled hypertension or cardiovascular disease", "Concurrent MAO inhibitor use", "Pregnancy and breastfeeding (no data)", "History of psychiatric illness or substance use disorder (dopaminergic drug, limited data)" ], "wada_status": "unclear", "fda_status": "unscheduled", "compounding_status": "Not FDA approved and not on any FDA compounding list as of the pages current to April 2026. It is a synthetic small molecule with no US marketing authorization and no 503A nomination, so there is no lawful basis for a US compounding pharmacy to dispense it. Some products sold online as tesofensine are unverified imports or research chemicals.", "typical_cost": "Not available through licensed US channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is tesofensine legal in the United States?", "a": "It is not FDA approved and is not on any FDA compounding list, so no US pharmacy can lawfully dispense it. Products sold online are unapproved drugs of unverified origin. PeptideAgent has not verified approval status in any other country.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Does tesofensine work for weight loss?", "a": "In the one published phase 2 randomized trial, yes: 203 obese adults lost a mean 11.3 kg on 0.5 mg and 12.8 kg on 1.0 mg over 24 weeks versus 2.2 kg on placebo, about 9 to 11% placebo adjusted. That is roughly double the effect of older oral anti-obesity drugs and in the range of semaglutide at 6 months, but it comes from a single 24 week study without a published phase 3 confirmation or long term safety data.", "source_ids": [ "astrup-2008", "doggrell-2009" ] }, { "q": "What are the side effects of tesofensine?", "a": "Dry mouth, nausea, constipation, insomnia, and dizziness were the common effects in the phase 2 trial. The important concern is cardiovascular: heart rate rose by about 7 beats per minute and blood pressure increased at the 1.0 mg dose, which is why the 0.5 mg dose was favored. Long term safety has not been established.", "source_ids": [ "astrup-2008" ] }, { "q": "How is tesofensine taken?", "a": "As a once daily oral tablet or capsule. The phase 2 trial tested 0.25, 0.5, and 1.0 mg daily for 24 weeks alongside a reduced calorie diet. These are trial doses for a drug that has not been approved in the US.", "source_ids": [ "astrup-2008" ] }, { "q": "How much does tesofensine cost?", "a": "There is no licensed US price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2" ] }, { "q": "Is tesofensine banned by WADA?", "a": "It is not named on the WADA Prohibited List, but two sections could capture it: S6 (stimulants) prohibits substances with similar chemical structure or biological effects to listed stimulants in competition, and S0 prohibits any pharmacological substance with no current approval by a governmental health authority. PeptideAgent marks it unclear; tested athletes should treat it as prohibited until their anti-doping organization says otherwise.", "source_ids": [ "wada-list" ] }, { "q": "Is tesofensine a peptide?", "a": "No. It is a small organic molecule (a phenyltropane derivative) taken by mouth. It appears on peptide vendor sites and in peptide clinic menus because it is marketed to the same weight loss customers, not because of its chemistry.", "source_ids": [ "astrup-2008" ] }, { "q": "Tesofensine vs semaglutide: which is better for weight loss?", "a": "Semaglutide has far stronger evidence: about 15% average weight loss at 68 weeks in a 1,961 person trial, proven cardiovascular benefit, and FDA approval. Tesofensine's 9 to 11% placebo adjusted loss comes from one 24 week study of 203 people with unresolved cardiovascular questions and no US approval. The comparison is between a proven, available drug and an unproven, unavailable one.", "source_ids": [ "astrup-2008", "doggrell-2009" ] } ], "studies": [ { "pmid": "18950853", "title": "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial", "year": 2008, "design": "Randomized, double blind, placebo controlled phase 2 trial, 24 weeks", "n": 203, "population": "Obese adults (BMI 30 to 40) on a hypocaloric diet", "outcome": "Weight loss 6.7 kg (0.25 mg), 11.3 kg (0.5 mg), 12.8 kg (1.0 mg) versus 2.2 kg placebo; dose related heart rate and blood pressure increases", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18950853/" }, { "pmid": "19548858", "title": "Tesofensine, a novel potent weight loss medicine. Evaluation of Astrup A et al. Lancet 2008", "year": 2009, "design": "Expert evaluation of the phase 2 trial", "population": "Obese adults from the 2008 trial", "outcome": "Confirms roughly twice the weight loss of existing oral agents and highlights cardiovascular safety questions for phase 3", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19548858/" } ], "sources": [ { "id": "astrup-2008", "type": "pubmed", "title": "Astrup A et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18950853/", "pmid": "18950853", "year": 2008 }, { "id": "doggrell-2009", "type": "pubmed", "title": "Doggrell SA. Tesofensine, a novel potent weight loss medicine. Expert Opin Investig Drugs 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19548858/", "pmid": "19548858", "year": 2009 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (sections S0 non-approved substances and S6 stimulants)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "semaglutide", "tirzepatide", "aod-9604", "5-amino-1mq" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "Tesofensine: weight loss evidence and legal status" } }, { "slug": "5-amino-1mq", "name": "5-Amino-1MQ", "aliases": [ "5-amino-1-methylquinolinium", "5-amino-1-methylquinolin-1-ium", "5A1MQ", "NNMT inhibitor 5-amino-1MQ", "5 amino 1mq", "5-amino-1MQ", "5-amino 1MQ" ], "class": "Oral small molecule nicotinamide N-methyltransferase (NNMT) inhibitor; not a peptide", "one_liner": "Not a peptide: an oral blocker of NNMT, an enzyme overactive in fat tissue, that cut fat in obese mice; no human trial published; not approved or compoundable.", "summary": "5-Amino-1MQ is a small molecule (a simple chemical drug, not a peptide) that blocks nicotinamide N-methyltransferase (NNMT), an enzyme that is overactive in fat tissue in obesity. In mice made obese by a high fat diet it reduced body weight and white fat mass (the body's main fat stores) over 11 days, and in aged mice it improved the function of muscle stem cells, the cells that repair muscle. No human trial of any kind has been published, it has no FDA approval or legal route to be compounded (custom-made by a pharmacy), and because it is unapproved everywhere it falls under WADA's S0 ban on unapproved substances.", "mechanism": "NNMT consumes nicotinamide and S-adenosylmethionine, lowering NAD+ precursors and the cell's methylation capacity; its expression rises in adipose tissue in obesity. 5-Amino-1MQ is a membrane permeable quinolinium compound that selectively inhibits NNMT, which in mouse adipocytes increases NAD+ and SAM, reduces lipogenesis, and increases energy expenditure. The compound also activated senescent muscle stem cells in aged mice. None of this has been demonstrated in humans.", "evidence_grade": "animal_only", "evidence_summary": "Two mouse studies from one University of Texas group. Neelakantan 2018: in diet induced obese mice, 11 days of 5-amino-1MQ reduced body weight, white adipose mass, and adipocyte size and lowered plasma cholesterol, without reducing food intake proportionally. Neelakantan 2019: in aged mice the compound activated senescent muscle stem cells and improved regeneration after injury. No human pharmacokinetic, safety, or efficacy study has been published as of the last verification date.", "human_evidence": "No indexed human study identified. Claims of fat loss, muscle gain, or metabolic benefit in people are extrapolated from mouse data and from vendor testimonials.", "animal_evidence": "Neelakantan 2018 (Biochem Pharmacol): diet induced obese mice given 5-amino-1MQ for 11 days lost body weight and white fat mass relative to vehicle, with smaller adipocytes and lower cholesterol; the compound was selective for NNMT and orally available. Neelakantan 2019 (Biochem Pharmacol): in 24 month old mice the inhibitor activated muscle stem cells and improved muscle regeneration and contractile function after injury. No long term toxicology has been published.", "conditions": [ "obesity" ], "literature_dosing": "Not established in human literature. Mouse studies used low milligram per kilogram daily doses (5 and 10 mg/kg in the aged muscle study); these rodent doses do not translate to a human regimen and no human dose finding study exists.", "routes": [ "Oral capsule (as sold)", "Subcutaneous or intraperitoneal injection and oral gavage (mouse studies)" ], "side_effects": [ "No human safety data of any kind published", "Mild nausea, headache, and appetite changes reported anecdotally", "Long term effects of NNMT inhibition (which alters NAD+ and methylation balance) in humans are unknown" ], "interactions": [ "No human interaction data exist", "Theoretical interaction with NAD+ precursors (nicotinamide, NMN, NR) because NNMT metabolizes nicotinamide" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S0 as a non-approved substance)", "Any use requiring an approved product: none exists" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Not FDA approved and not an active ingredient in any approved drug. It does not appear in FDA's Category 2 list or on the 503A bulks list as of the pages current to April 2026, and it has no USP monograph, so it does not meet any of the three bulk substance criteria in section 503A. That leaves no lawful basis for a compounding pharmacy to dispense it despite its widespread marketing as a compounded capsule. It was not part of the July 2026 advisory committee review.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product, not nominated for the 503A bulks list, and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "What is 5-Amino-1MQ?", "a": "5-Amino-1MQ is a small molecule, not a peptide, that blocks nicotinamide N-methyltransferase (NNMT), an enzyme that is overactive in fat tissue in obesity. It is sold as capsules for fat loss and muscle, but its only published evidence is two short mouse studies. It is not FDA approved, is not on the 503A bulks list (FDA's list of raw ingredients pharmacies may use to compound drugs for individual patients), and has no lawful compounded source.", "source_ids": [ "neelakantan-2018", "neelakantan-2019", "fda-503a-bulks" ] }, { "q": "Is 5-Amino-1MQ legal in the United States?", "a": "It is not FDA approved, is not on the 503A bulks list, and has no USP monograph, so a compounding pharmacy has no lawful basis to dispense it even though it is widely marketed as a compounded capsule. It is also absent from FDA's Category 2 list, which means FDA has not formally reviewed it, not that it has been cleared. Possession is not a crime.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "5-Amino-1MQ benefits: does it work for fat loss?", "a": "In diet induced obese mice, an 11 day course reduced body weight and white fat mass and shrank fat cells. In humans there is no evidence either way, because no clinical trial has been published. PeptideAgent grades it animal-only.", "source_ids": [ "neelakantan-2018" ] }, { "q": "What are the side effects of 5-Amino-1MQ?", "a": "Unknown. No human safety, pharmacokinetic, or toxicology study has been published. Anecdotal reports mention nausea, headache, and appetite changes. Because NNMT inhibition changes NAD+ and methylation balance throughout the body, long term effects cannot be predicted from the two short mouse studies.", "source_ids": [ "neelakantan-2018", "neelakantan-2019" ] }, { "q": "How is 5-Amino-1MQ taken?", "a": "Products sold online are oral capsules. The mouse studies gave it by injection or by mouth, and their doses do not translate to people. No human dose has been established. PeptideAgent does not give doses for unapproved peptides.", "source_ids": [ "neelakantan-2018" ] }, { "q": "How much does 5-Amino-1MQ cost?", "a": "There is no licensed price because no lawful product exists, and purity of these products is not verified. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is 5-Amino-1MQ banned by WADA?", "a": "It is not named on the list, but section S0 of the WADA Prohibited List prohibits at all times any pharmacological substance that has no current approval by a governmental health authority for human therapeutic use. 5-Amino-1MQ has no approval anywhere, so it falls under S0.", "source_ids": [ "wada-list" ] }, { "q": "Is 5-Amino-1MQ a peptide?", "a": "No. It is a small aromatic molecule (a methylquinolinium salt). It is sold by peptide vendors and clinics alongside injectable peptides, which is the only reason it appears in peptide directories.", "source_ids": [ "neelakantan-2018" ] }, { "q": "Does 5-Amino-1MQ build muscle?", "a": "In 24 month old mice, NNMT inhibition activated senescent muscle stem cells and improved regeneration after injury. That is a repair finding in old animals, not a muscle building finding, and it has not been tested in people.", "source_ids": [ "neelakantan-2019" ] } ], "studies": [ { "pmid": "29155147", "title": "Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice", "year": 2018, "design": "Mouse diet induced obesity model, 11 day treatment", "population": "Diet induced obese mice", "outcome": "Reduced body weight, white adipose mass, adipocyte size, and plasma cholesterol versus vehicle", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/29155147/" }, { "pmid": "30753815", "title": "Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle", "year": 2019, "design": "Aged mouse muscle injury model", "population": "24 month old mice", "outcome": "Activated muscle stem cells and improved regeneration and contractile recovery after injury", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/30753815/" } ], "sources": [ { "id": "neelakantan-2018", "type": "pubmed", "title": "Neelakantan H et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29155147/", "pmid": "29155147", "year": 2018 }, { "id": "neelakantan-2019", "type": "pubmed", "title": "Neelakantan H et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30753815/", "pmid": "30753815", "year": 2019 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "nad-plus", "aod-9604", "tesofensine", "mots-c" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 3, "seo": { "title": "5-Amino-1MQ: benefits, side effects, and legal status", "description": "What 5-Amino-1MQ is (a small molecule NNMT inhibitor, not a peptide), what the mouse fat loss studies show, side effects, and its US legal status.", "h1": "5-Amino-1MQ (NNMT inhibitor)", "headings": { "evidence": "5-amino-1MQ benefits: what the evidence shows", "safety": "5-amino-1MQ side effects" } } }, { "slug": "adipotide", "name": "Adipotide", "aliases": [ "Prohibitin-TP01", "FTPP", "Fat targeted proapoptotic peptide", "CKGGRAKDC-GG-D(KLAKLAK)2" ], "class": "Synthetic peptidomimetic: a fat vasculature homing sequence fused to a proapoptotic D amino acid peptide", "one_liner": "Experimental peptide that kills blood vessels feeding white fat; 11% weight loss in obese monkeys with kidney damage; no human results published.", "summary": "Adipotide is an experimental peptidomimetic (a lab-made, peptide-like molecule) that targets prohibitin, a protein on the blood vessels of white fat, and makes those vessel cells die, starving the fat tissue. It reversed obesity in mice in 2004 and produced about 11% body weight loss with improved insulin resistance in obese rhesus monkeys over 4 weeks in 2011, but caused kidney injury that limited the dose. A phase 1 trial (a first, small safety study in people) in men with prostate cancer was started and no human results have been published, so the evidence is animal-only, and it has no approval anywhere and no legal route to be compounded (custom-made by a pharmacy).", "mechanism": "The CKGGRAKDC homing motif binds prohibitin, a protein exposed on endothelial cells of white adipose tissue vasculature. The fused D(KLAKLAK)2 sequence disrupts mitochondrial membranes once internalized, causing apoptosis of those endothelial cells. Loss of blood supply leads to fat cell death and resorption, with a secondary reduction in food intake reported in monkeys. Prohibitin is also present in kidney, which is thought to explain the renal toxicity.", "evidence_grade": "animal_only", "evidence_summary": "Two landmark animal studies. Kolonin 2004 (Nat Med) showed targeted ablation of white fat vasculature reversed diet induced obesity in mice. Barnhart 2011 (Sci Transl Med) treated obese rhesus monkeys for 4 weeks and found about 11% body weight loss, a 38% reduction in abdominal fat by imaging, and improved insulin resistance, with reversible dose dependent kidney tubular injury. No human data have been published.", "human_evidence": "No indexed human study identified. A phase 1 dose escalation study in men with prostate cancer and obesity was registered at a US cancer center around 2011 to evaluate safety; results have not been published as of the last verification date.", "animal_evidence": "Kolonin 2004: daily subcutaneous injection in diet induced obese mice ablated white fat vasculature, caused rapid weight loss, and reversed obesity with normalization of metabolic markers. Barnhart 2011: 10 obese rhesus monkeys received daily subcutaneous injections for 28 days and lost a mean 11% of body weight (versus 1.5% in lean controls), with a 27% reduction in body mass index, 38% reduction in abdominal fat, improved insulin sensitivity by clamp, and reduced food intake; renal tubular effects were dose dependent and reversible in the monkeys but flagged as the main safety concern.", "conditions": [ "obesity" ], "literature_dosing": "Not established in human literature. Monkeys received about 0.43 mg/kg subcutaneously daily for 28 days; mice received daily subcutaneous doses in the milligram per kilogram range. These animal doses do not translate to a human regimen and no human dose has been published.", "routes": [ "Subcutaneous injection (animal studies and as sold)" ], "side_effects": [ "Kidney injury (dose dependent renal tubular damage in monkeys, the dose limiting toxicity)", "Dehydration and reduced food intake in monkeys", "No human safety data published", "Injection site reactions reported anecdotally" ], "interactions": [ "No human interaction data exist", "Theoretical additive kidney risk with NSAIDs, aminoglycosides, and other nephrotoxic drugs based on monkey toxicity" ], "contraindications": [ "Any kidney disease or reduced kidney function", "Pregnancy and breastfeeding (no data)", "Athletes subject to WADA testing (prohibited at all times under S0)", "Any use requiring an approved product: none exists" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Not FDA approved and not on any FDA compounding list as of the pages current to April 2026. Adipotide has never been nominated for the 503A bulks list and has no USP monograph, so no compounding pharmacy has a lawful basis to dispense it. It remains an investigational compound with unpublished phase 1 results.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date outside a registered clinical trial. Clinical development stopped after phase 1.", "Not available as an FDA approved product and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is adipotide legal in the United States?", "a": "It is not FDA approved, has never been nominated for the 503A bulks list (FDA's list of raw ingredients pharmacies may use to compound drugs for individual patients), and has no USP monograph (an official drug quality standard), so no pharmacy can lawfully compound it. It has not gone through FDA's Category 2 review (FDA's safety screen of nominated compounding ingredients) because nobody has nominated it. Possession is not a crime, but research chemical products are not for human use.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Does adipotide work for weight loss?", "a": "In animals, dramatically: obese mice reversed their obesity, and obese rhesus monkeys lost about 11% of body weight and 38% of abdominal fat in 4 weeks with improved insulin sensitivity. In humans nobody knows, because the only human trial (a phase 1 safety study in prostate cancer patients) has not published results. The monkey study also showed kidney toxicity, which is why development has been slow.", "source_ids": [ "kolonin-2004", "barnhart-2011" ] }, { "q": "What are the side effects of adipotide?", "a": "The known problem is kidney damage: in monkeys, adipotide caused dose dependent injury to the renal tubules that was reversible after stopping, and this was the dose limiting toxicity. Monkeys also ate less and needed hydration monitoring. There are no human safety data.", "source_ids": [ "barnhart-2011" ] }, { "q": "How is adipotide taken?", "a": "In animal studies it was a daily subcutaneous injection: about 0.43 mg/kg for 28 days in monkeys. Products sold online are subcutaneous injection vials. No human dose has been established.", "source_ids": [ "barnhart-2011", "kolonin-2004" ] }, { "q": "How much does adipotide cost?", "a": "There is no licensed price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is adipotide banned by WADA?", "a": "It is not named on the list, but section S0 of the WADA Prohibited List prohibits at all times any substance with no current approval by any governmental health authority for human use. Adipotide has no approval anywhere, so it is prohibited under S0.", "source_ids": [ "wada-list" ] }, { "q": "Adipotide vs semaglutide: how do they compare?", "a": "Semaglutide is FDA approved with about 15% weight loss at 68 weeks in a 1,961 person trial and proven heart benefit. Adipotide has a 10 monkey study, no published human data, and kidney toxicity as its main signal. They also work in opposite ways: semaglutide reduces appetite through a gut hormone receptor, adipotide destroys the blood supply of fat tissue. Only one of them is a treatment option.", "source_ids": [ "barnhart-2011" ] } ], "studies": [ { "pmid": "15133506", "title": "Reversal of obesity by targeted ablation of adipose tissue", "year": 2004, "design": "Mouse diet induced obesity model with daily subcutaneous peptide", "population": "Diet induced obese mice", "outcome": "Ablation of white fat vasculature caused rapid weight loss and reversed obesity", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/15133506/" }, { "pmid": "22072637", "title": "A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys", "year": 2011, "design": "Non human primate treatment study, 28 days", "n": 10, "population": "Spontaneously obese rhesus monkeys", "outcome": "About 11% body weight loss, 38% reduction in abdominal fat, improved insulin sensitivity; reversible dose dependent renal tubular toxicity", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/22072637/" } ], "sources": [ { "id": "kolonin-2004", "type": "pubmed", "title": "Kolonin MG et al. Reversal of obesity by targeted ablation of adipose tissue. Nat Med 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15133506/", "pmid": "15133506", "year": 2004 }, { "id": "barnhart-2011", "type": "pubmed", "title": "Barnhart KF et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/22072637/", "pmid": "22072637", "year": 2011 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "aod-9604", "semaglutide", "tesofensine", "5-amino-1mq" ], "cluster": "metabolic", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "setmelanotide", "name": "Setmelanotide", "aliases": [ "Imcivree", "RM-493", "BIM-22493", "Setmelanotide acetate" ], "class": "Cyclic 8 amino acid melanocortin-4 receptor (MC4R) agonist", "one_liner": "FDA approved hunger-pathway (MC4R) drug for rare genetic obesity (POMC, PCSK1, LEPR, Bardet-Biedl) and acquired hypothalamic obesity; not for common obesity.", "summary": "Setmelanotide (Imcivree) is an FDA approved daily injectable melanocortin-4 receptor agonist, a drug that activates a brain receptor controlling hunger, for chronic weight management in people with obesity caused by POMC, PCSK1, or LEPR deficiency, rare gene defects in that hunger pathway (approved November 2020), or Bardet-Biedl syndrome, a rare inherited disorder (June 2022), with the age range extended to 2 years and older in December 2024, and extended in March 2026 to acquired hypothalamic obesity (obesity after damage to the hypothalamus) in patients 4 and older. In phase 3 trials, 80% of POMC deficient and 45% of LEPR deficient patients lost at least 10% of body weight at one year, and about one third of Bardet-Biedl patients did. It is not approved or effective for common obesity, and it is prescription only.", "mechanism": "Setmelanotide activates the melanocortin-4 receptor in the hypothalamus, restoring the satiety signal that is lost when upstream leptin to POMC to MC4R signaling is broken by genetic variants. Unlike earlier MC4R agonists it has little effect on blood pressure at approved doses. Activation of MC1R in skin causes darkening of skin and hair.", "evidence_grade": "human_rct", "evidence_summary": "Phase 3 evidence in rare genetic obesity. Clement 2020: single arm phase 3 trials in POMC or PCSK1 deficiency (n = 10; 8 of 10 achieved at least 10% weight loss, mean 25.6% loss at 1 year) and LEPR deficiency (n = 11; 5 of 11 achieved at least 10%, mean 12.5% loss), with large reductions in hunger scores. Haqq 2022: randomized placebo controlled phase 3 in Bardet-Biedl and Alstrom syndrome (n = 38 randomized, 14 week placebo period then open label to 52 weeks); at 52 weeks about one third of Bardet-Biedl patients aged 12 and older achieved at least 10% weight loss. Roth 2025: phase 3 in children aged 2 to 5 showed BMI reductions. In the randomized phase 3 TRANSCEND trial in acquired hypothalamic obesity (n = 142), BMI fell 15.8% versus a 2.6% rise on placebo at 52 weeks, a placebo adjusted difference of 18.4% (manufacturer reported). An earlier study in common obesity showed no meaningful effect at tolerable doses.", "human_evidence": "Kuhnen 2016 (NEJM): two adults with POMC deficiency lost 51 kg over 42 weeks and 20.5 kg over 12 weeks, with normalization of hunger. Clement 2020 (Lancet Diabetes Endocrinol): 80% of POMC deficient participants and 45% of LEPR deficient participants achieved at least 10% weight loss at 1 year; mean hunger score fell by 27% and 44%. Haqq 2022: in Bardet-Biedl syndrome, mean BMI fell about 6% during the 14 week placebo controlled period on setmelanotide versus a small change on placebo, and 32% of patients aged 12 and older lost at least 10% of body weight at 52 weeks. Roth 2025: in children aged 2 to 5 with POMC, PCSK1, LEPR deficiency or Bardet-Biedl syndrome, BMI z scores fell substantially over 52 weeks.", "animal_evidence": "Rodent and primate studies established that MC4R agonism reduces food intake and body weight and that setmelanotide, unlike earlier compounds, does not raise blood pressure in primates. Animal data guided the human program; the clinically relevant evidence is human.", "conditions": [ "obesity" ], "literature_dosing": "FDA label (Imcivree, DailyMed; subcutaneous once daily): starting doses are 2 mg daily for 2 weeks in patients 12 and older with Bardet-Biedl syndrome or POMC, PCSK1, or LEPR deficiency, 1 mg daily for 2 weeks at ages 6 to under 12, and 0.5 mg daily for 2 weeks at ages 2 to under 6; acquired hypothalamic obesity starts at 0.5 mg daily for 2 weeks in patients 4 and older. The maintenance dose is 3 mg daily for all indications at ages 6 and older, while younger children use a weight based maintenance dose. The label has separate dosing for renal impairment.", "routes": [ "Subcutaneous injection once daily" ], "side_effects": [ "Injection site reactions (96% in trials)", "Skin hyperpigmentation and darkening of moles and hair (78%)", "Nausea (56%) and vomiting", "Headache", "Diarrhea and abdominal pain", "Spontaneous penile erection in males and sexual adverse reactions in females", "Depression and suicidal ideation (label warning; monitor mood)", "Fatigue" ], "interactions": [ "No formal drug interaction studies; the label reports no clinically significant pharmacokinetic interactions", "Other melanocortin agonists (bremelanotide, melanotan II): additive MC receptor effects, not studied", "Antidepressants: monitor mood given the depression warning, no direct interaction established" ], "contraindications": [ "None listed in the label as absolute contraindications", "Not indicated for obesity due to suspected POMC, PCSK1, or LEPR variants classified as benign or likely benign, or for common polygenic obesity", "Pregnancy: weight loss offers no benefit and may harm the fetus; label advises discontinuation", "History of depression or suicidal ideation requires careful monitoring" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved product (Imcivree, November 2020 for POMC, PCSK1, and LEPR deficiency obesity; June 2022 for Bardet-Biedl syndrome; December 2024 expansion to ages 2 and older). It is available only by prescription and requires a confirmed genetic diagnosis for coverage. Because an approved product exists and is not in shortage, compounding is not permitted except for a documented patient specific clinical need. Setmelanotide is not on any FDA compounding bulks list. The current label also covers acquired hypothalamic obesity in patients 4 years and older.", "typical_cost": "List price is in the hundreds of thousands of USD per year. Patients with a confirmed qualifying genetic diagnosis are usually covered by insurance with manufacturer support programs; out of pocket cost without coverage is prohibitive.", "access_path": [ "Prescription from a specialist after genetic confirmation of an eligible condition, dispensed through a specialty pharmacy as Imcivree.", "Not available through compounding pharmacies, telehealth peptide clinics, or for general weight loss." ], "faqs": [ { "q": "Is setmelanotide (Imcivree) FDA approved, and what is it used for?", "a": "Yes. The Imcivree label covers reducing excess body weight and maintaining the reduction long term in patients 4 and older with acquired hypothalamic obesity (obesity after damage to the brain's hunger control center), and in patients 2 and older with Bardet-Biedl syndrome (a rare inherited disorder) or with POMC, PCSK1, or LEPR deficiency (rare gene defects in the hunger pathway) confirmed by genetic testing showing variants interpreted as pathogenic (disease causing), likely pathogenic, or of uncertain significance. It is not approved for common obesity.", "source_ids": [ "fda-imcivree-label" ] }, { "q": "Does setmelanotide work for regular obesity?", "a": "No. It works when the MC4R pathway upstream signal is genetically broken. In POMC deficiency 8 of 10 phase 3 participants lost at least 10% of body weight (mean 25.6%), and in LEPR deficiency 5 of 11 did. In people with common obesity an earlier study found no meaningful weight loss at tolerable doses, and it is not approved for them. Genetic testing comes first.", "source_ids": [ "clement-2020", "fda-imcivree-label" ] }, { "q": "What are the side effects of setmelanotide?", "a": "Injection site reactions (96%), skin darkening and darkening of moles and hair (78%), nausea (56%), vomiting, headache, and diarrhea were the common effects in trials. Males can experience spontaneous erections. The label carries a warning for depression and suicidal ideation, so mood should be monitored. Skin darkening reverses after stopping.", "source_ids": [ "fda-imcivree-label", "clement-2020" ] }, { "q": "What is the setmelanotide (Imcivree) dose on the FDA label?", "a": "A once daily injection under the skin. For Bardet-Biedl syndrome and POMC, PCSK1, or LEPR deficiency, patients 12 and older start at 2 mg for 2 weeks, children 6 to 11 at 1 mg, and children 2 to 5 at 0.5 mg. For acquired hypothalamic obesity, patients 4 and older start at 0.5 mg for 2 weeks. The maintenance dose from age 6 is 3 mg daily; younger children use weight based doses.", "source_ids": [ "fda-imcivree-label" ] }, { "q": "How much does setmelanotide cost?", "a": "The list price is in the hundreds of thousands of USD per year, in line with other rare disease drugs. Insurance generally covers it only with a confirmed qualifying genetic diagnosis, and the manufacturer runs patient support programs. Without coverage the cost is prohibitive. Prices verified on the last verified date.", "source_ids": [ "fda-imcivree-label" ] }, { "q": "Is setmelanotide banned by WADA?", "a": "It is not named on the WADA Prohibited List as of the 2026 list or the 2027 list published in September 2026, and because it is an approved drug the S0 non-approved substance rule does not apply. Athletes with a genetic obesity diagnosis should still confirm with their anti-doping organization and consider a therapeutic use exemption if required by their federation.", "source_ids": [ "wada-list", "wada-2027-list" ] }, { "q": "Setmelanotide vs semaglutide: which is better?", "a": "They serve different patients. Semaglutide treats common obesity and type 2 diabetes with about 15% weight loss at 68 weeks. Setmelanotide treats rare genetic obesity, where it produces 12 to 26% mean weight loss in the phase 3 trials and restores satiety that GLP-1 drugs do not fully address. For someone without a confirmed POMC, PCSK1, LEPR, or Bardet-Biedl diagnosis, setmelanotide is not an option.", "source_ids": [ "clement-2020", "haqq-2022" ] }, { "q": "Does setmelanotide help Bardet-Biedl syndrome?", "a": "Yes, modestly. In the placebo controlled phase 3 trial, BMI fell about 6% on setmelanotide during the 14 week blinded period versus little change on placebo, and after 52 weeks about one third of patients aged 12 and older had lost at least 10% of body weight, with reduced hunger scores. FDA approved this indication in June 2022.", "source_ids": [ "haqq-2022", "fda-imcivree-label" ] } ], "studies": [ { "pmid": "27468060", "title": "Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist", "year": 2016, "design": "Open label treatment of two patients", "n": 2, "population": "Adults with POMC deficiency obesity", "outcome": "Weight loss of 51 kg over 42 weeks and 20.5 kg over 12 weeks with normalization of hunger", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/27468060/" }, { "pmid": "33137293", "title": "Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials", "year": 2020, "design": "Two single arm open label phase 3 trials, 1 year", "n": 21, "population": "Patients aged 6 and older with POMC or PCSK1 deficiency (n = 10) or LEPR deficiency (n = 11)", "outcome": "80% of POMC and 45% of LEPR participants achieved at least 10% weight loss; mean weight loss 25.6% and 12.5%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33137293/" }, { "pmid": "36356613", "title": "Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period", "year": 2022, "design": "Randomized, double blind, placebo controlled 14 weeks then open label to 52 weeks", "n": 38, "population": "Patients aged 6 and older with Bardet-Biedl or Alstrom syndrome", "outcome": "Greater BMI reduction versus placebo at 14 weeks; 32% of Bardet-Biedl patients aged 12 and older achieved at least 10% weight loss at 52 weeks", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36356613/" }, { "pmid": "39549717", "title": "Setmelanotide for the treatment of severe early-childhood genetic obesity", "year": 2025, "design": "Open label phase 3 trial, 52 weeks", "population": "Children aged 2 to 5 with POMC, PCSK1, or LEPR deficiency or Bardet-Biedl syndrome", "outcome": "Substantial reductions in BMI z score over 52 weeks, supporting the age expansion", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/39549717/" } ], "sources": [ { "id": "kuhnen-2016", "type": "pubmed", "title": "Kuhnen P et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27468060/", "pmid": "27468060", "year": 2016 }, { "id": "clement-2020", "type": "pubmed", "title": "Clement K et al. Efficacy and safety of setmelanotide in individuals with severe obesity due to LEPR or POMC deficiency: phase 3 trials. Lancet Diabetes Endocrinol 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33137293/", "pmid": "33137293", "year": 2020 }, { "id": "haqq-2022", "type": "pubmed", "title": "Haqq AM et al. Efficacy and safety of setmelanotide in patients with Bardet-Biedl syndrome and Alstrom syndrome: phase 3 trial. Lancet Diabetes Endocrinol 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36356613/", "pmid": "36356613", "year": 2022 }, { "id": "roth-2025", "type": "pubmed", "title": "Roth CL et al. Setmelanotide for the treatment of severe early-childhood genetic obesity. Lancet Diabetes Endocrinol 2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39549717/", "pmid": "39549717", "year": 2025 }, { "id": "fda-imcivree-label", "type": "fda", "title": "FDA prescribing information for Imcivree (setmelanotide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-2027-list", "type": "wada", "title": "WADA 2027 Prohibited List (published September 21, 2026, in force January 1, 2027)", "url": "https://www.wada-ama.org/en/resources/2027-prohibited-list", "year": 2026 }, { "id": "imcivree-aho-approval", "type": "other", "title": "Manufacturer press release: FDA approval of Imcivree for acquired hypothalamic obesity (March 19, 2026)", "url": "https://www.globenewswire.com/news-release/2026/03/19/3259502/0/en/rhythm-pharmaceuticals-announces-fda-approval-of-imcivree-setmelanotide-for-patients-with-acquired-hypothalamic-obesity.html", "year": 2026 } ], "related": [ "melanotan-ii", "pt-141", "semaglutide", "tirzepatide" ], "cluster": "metabolic", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Setmelanotide (Imcivree): uses, side effects, and dosing", "description": "Imcivree is setmelanotide, a daily MC4 receptor agonist for rare genetic obesity and acquired hypothalamic obesity. FDA label uses, doses, and side effects.", "h1": "Setmelanotide (Imcivree)" } }, { "slug": "pramlintide", "name": "Pramlintide", "aliases": [ "Symlin", "SymlinPen", "Pramlintide acetate", "AC137", "Synthetic amylin analog" ], "class": "Synthetic 37 amino acid analog of human amylin (three proline substitutions to prevent aggregation)", "one_liner": "FDA approved lab-made amylin used with mealtime insulin; lowers HbA1c about 0.3 to 0.4 points more than placebo, modest weight loss, boxed low sugar warning.", "summary": "Pramlintide (Symlin) is an FDA approved injectable analog (lab-made version) of amylin, the hormone released with insulin that slows gastric emptying (how fast food leaves the stomach) and suppresses glucagon, a blood sugar raising hormone, after meals. Approved in March 2005 as an add-on to mealtime insulin in type 1 and type 2 diabetes, it lowers HbA1c (a measure of average blood sugar over about 3 months) by roughly 0.3 to 0.4 percentage points more than placebo over a year and produces about 1 to 2 kg of weight loss instead of the weight gain seen with insulin alone. It carries a boxed warning, FDA's most serious label warning, for severe insulin induced hypoglycemia (low blood sugar) and is prescription only.", "mechanism": "Pramlintide acts at amylin receptors (calcitonin receptor with RAMP proteins) in the brainstem area postrema. This slows gastric emptying, suppresses inappropriate post meal glucagon secretion, and reduces food intake through central satiety signaling. It has no direct effect on insulin secretion or action. Human amylin aggregates into amyloid fibrils; the three proline substitutions in pramlintide prevent that so it can be formulated for injection.", "evidence_grade": "human_rct", "evidence_summary": "Multiple 1 year randomized placebo controlled trials as an add-on to insulin. Whitehouse 2002 (type 1 diabetes, n = 480, 52 weeks): HbA1c fell about 0.4 points on pramlintide versus 0.1 on placebo with a weight difference of about 1 kg. Hollander 2003 (type 2 diabetes on insulin, n = 656, 52 weeks): 120 ug twice daily lowered HbA1c by 0.62 points versus 0.22 with placebo and reduced weight by 1.4 kg versus a 0.7 kg gain. Aronne 2007 (obesity without diabetes, n = 204, 16 weeks): dose escalation to 240 ug three times daily produced about 3.6 kg placebo corrected weight loss.", "human_evidence": "Whitehouse 2002: 480 adults with type 1 diabetes randomized to pramlintide 30 or 60 ug with meals or placebo added to insulin for 52 weeks; HbA1c reduction was greater with pramlintide (about 0.4 versus 0.1 percentage points) and weight was about 1 kg lower, with more nausea and severe hypoglycemia in the first weeks. Hollander 2003: 656 insulin treated adults with type 2 diabetes; 120 ug twice daily reduced HbA1c by 0.62 versus 0.22 points and weight by 1.4 kg versus a 0.7 kg gain over 52 weeks, with insulin doses unchanged. Aronne 2007: 204 obese adults without diabetes; pramlintide up to 240 ug three times daily produced placebo corrected weight loss of about 3.6 kg at 16 weeks with nausea as the main adverse effect. Pramlintide is also the template for cagrilintide, the long acting amylin analog now in phase 3 with semaglutide.", "animal_evidence": "Rodent studies established amylin's effects on gastric emptying, glucagon suppression, and food intake, and showed that pramlintide reproduces them without forming amyloid. Animal data are supportive; the evidence base is human.", "conditions": [ "type-2-diabetes", "obesity" ], "literature_dosing": "FDA label (Symlin, DailyMed): when starting, mealtime insulin is reduced by 50%. Type 1 diabetes: 15 mcg subcutaneously before major meals, increased in 15 mcg steps to a maintenance dose of 30 or 60 mcg as tolerated. Type 2 diabetes: 60 mcg before major meals, increased to 120 mcg as tolerated. The label advises at least 3 days between dose steps to limit nausea, and carries a boxed warning for severe hypoglycemia with insulin, occurring within 3 hours of an injection. Symlin and insulin are always given as separate injections.", "routes": [ "Subcutaneous injection before major meals (pen device)" ], "side_effects": [ "Nausea (28 to 48% in trials, highest in type 1 diabetes and during titration)", "Severe hypoglycemia when insulin is not reduced (boxed warning; risk within 3 hours of injection)", "Reduced appetite and vomiting", "Headache", "Injection site reactions", "Fatigue and dizziness" ], "interactions": [ "Insulin: mealtime insulin must be reduced by about 50% at initiation to prevent severe hypoglycemia", "Oral medications that need rapid absorption (for example analgesics): take 1 hour before or 2 hours after pramlintide because of delayed gastric emptying", "Anticholinergics and other drugs that slow gastric motility: additive effect, not recommended", "GLP-1 receptor agonists: additive slowing of gastric emptying, combination not studied in labeling" ], "contraindications": [ "Confirmed gastroparesis", "Hypoglycemia unawareness", "Hypersensitivity to pramlintide or metacresol", "Not for patients with poor adherence to insulin or glucose monitoring, or HbA1c above 9% (label warnings)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved product (Symlin, March 2005) for type 1 and type 2 diabetes in patients using mealtime insulin who have not achieved glucose control. It is prescription only. Because an approved product is available and not in shortage, compounding is not permitted except for a documented patient specific clinical need. Pramlintide is not on any FDA compounding bulks list and is not sold through peptide vendors in any meaningful way.", "typical_cost": "List price is well over 1,000 USD per month for SymlinPen at typical doses; commercial insurance copays vary and coverage often requires prior authorization. Prices verified on the last verified date.", "access_path": [ "Prescription from an endocrinologist or primary care provider filled at a retail or specialty pharmacy as Symlin.", "Not available through compounding pharmacies or telehealth peptide clinics." ], "faqs": [ { "q": "Is pramlintide (Symlin) FDA approved, and what is it used for?", "a": "Yes. Symlin was approved in March 2005. Its label covers adjunctive (add-on) treatment of type 1 or type 2 diabetes in patients who use mealtime insulin and have not reached glucose goals despite optimal insulin therapy. It is the only amylin analog (lab-made version of the hormone amylin) approved in the US, it is prescription only, and it is not approved for weight loss.", "source_ids": [ "fda-symlin-label" ] }, { "q": "Does pramlintide help with weight loss?", "a": "Modestly. In 1 year diabetes trials it produced about 1 to 2 kg less weight than placebo while insulin alone caused weight gain. In a 16 week trial in 204 obese adults without diabetes, doses up to 240 ug three times daily gave about 3.6 kg placebo corrected weight loss. Its long acting cousin cagrilintide, combined with semaglutide, is the compound being developed for weight loss.", "source_ids": [ "hollander-2003", "aronne-2007" ] }, { "q": "What are the side effects of pramlintide?", "a": "Nausea is the main one, affecting roughly 28 to 48% of trial participants and easing after titration. The serious risk is severe hypoglycemia in the 3 hours after injection when mealtime insulin is not reduced, which is why the label has a boxed warning and requires cutting mealtime insulin by half at the start. Headache, vomiting, and reduced appetite are also reported.", "source_ids": [ "fda-symlin-label", "whitehouse-2002" ] }, { "q": "What is the pramlintide (Symlin) dose on the FDA label?", "a": "A subcutaneous injection before each major meal, with mealtime insulin cut by 50% at the start. Type 1 diabetes starts at 15 mcg and rises in 15 mcg steps to 30 or 60 mcg; type 2 diabetes starts at 60 mcg and rises to 120 mcg, waiting at least 3 days between steps. It is never mixed with insulin in the same syringe, and the boxed warning covers severe hypoglycemia within 3 hours of a dose.", "source_ids": [ "fda-symlin-label" ] }, { "q": "How much does pramlintide cost?", "a": "SymlinPen's list price is well over 1,000 USD per month at typical doses. Commercial and Medicare coverage varies and often requires prior authorization; manufacturer savings programs have been offered. Prices verified on the last verified date and change.", "source_ids": [ "fda-symlin-label" ] }, { "q": "Is pramlintide banned by WADA?", "a": "No. Pramlintide is not on the WADA Prohibited List. Insulin, which it is used alongside, is prohibited under section S4, so athletes with diabetes need a therapeutic use exemption for their insulin regardless.", "source_ids": [ "wada-list" ] }, { "q": "Pramlintide vs semaglutide: which is better for type 2 diabetes?", "a": "Semaglutide, for most people. It lowers HbA1c by 1 to 1.5 points, produces about 15% weight loss at the weight management dose, reduces cardiovascular events, and is given weekly. Pramlintide lowers HbA1c by about 0.3 to 0.4 points more than placebo, gives 1 to 2 kg of weight loss, needs injection before each meal, and works only alongside insulin. Pramlintide's niche is type 1 diabetes, where GLP-1 agonists are not approved.", "source_ids": [ "hollander-2003", "whitehouse-2002" ] }, { "q": "Can pramlintide be used in type 1 diabetes?", "a": "Yes, and it is the main use. In a 52 week trial of 480 adults with type 1 diabetes, pramlintide added to insulin lowered HbA1c by about 0.4 points versus 0.1 with placebo and prevented weight gain. The trade-off is nausea and an early increase in severe hypoglycemia until insulin doses are adjusted.", "source_ids": [ "whitehouse-2002", "fda-symlin-label" ] } ], "studies": [ { "pmid": "11919132", "title": "A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes", "year": 2002, "design": "Randomized, double blind, placebo controlled trial, 52 weeks, with open label extension", "n": 480, "population": "Adults with type 1 diabetes on insulin", "outcome": "Greater HbA1c reduction (about 0.4 versus 0.1 percentage points) and about 1 kg lower weight than placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/11919132/" }, { "pmid": "12610038", "title": "Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial", "year": 2003, "design": "Randomized, double blind, placebo controlled trial, 52 weeks", "n": 656, "population": "Insulin treated adults with type 2 diabetes", "outcome": "120 ug twice daily lowered HbA1c by 0.62 versus 0.22 points and weight by 1.4 kg versus a 0.7 kg gain", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/12610038/" }, { "pmid": "17504894", "title": "Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study", "year": 2007, "design": "Randomized, double blind, placebo controlled dose escalation trial, 16 weeks", "n": 204, "population": "Obese adults without diabetes", "outcome": "About 3.6 kg placebo corrected weight loss at doses up to 240 ug three times daily", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/17504894/" } ], "sources": [ { "id": "whitehouse-2002", "type": "pubmed", "title": "Whitehouse F et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care 2002", "url": "https://pubmed.ncbi.nlm.nih.gov/11919132/", "pmid": "11919132", "year": 2002 }, { "id": "hollander-2003", "type": "pubmed", "title": "Hollander PA et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12610038/", "pmid": "12610038", "year": 2003 }, { "id": "aronne-2007", "type": "pubmed", "title": "Aronne L et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007", "url": "https://pubmed.ncbi.nlm.nih.gov/17504894/", "pmid": "17504894", "year": 2007 }, { "id": "fda-symlin-label", "type": "fda", "title": "FDA prescribing information for Symlin (pramlintide acetate) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff", "year": 2024 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "cagrilintide", "insulin", "semaglutide", "glucagon" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Pramlintide (Symlin): uses, side effects, and dosing", "description": "Symlin is pramlintide, a mealtime amylin analog injection for type 1 and type 2 diabetes on insulin. FDA label use, dose steps, hypoglycemia warning, cost.", "h1": "Pramlintide (Symlin)" } }, { "slug": "insulin", "name": "Insulin", "aliases": [ "Human insulin", "Insulin analogs", "Insulin glargine", "Insulin lispro", "Insulin aspart", "Insulin degludec", "Humulin", "Novolin", "Lantus", "Humalog", "NovoLog" ], "class": "51 amino acid peptide hormone (two chains linked by disulfide bonds) and its recombinant analogs", "one_liner": "The original peptide drug: FDA approved since 1923, essential in type 1 diabetes, proven to cut complications by 25 to 76%; WADA banned without an exemption.", "summary": "Insulin is the peptide hormone that lets cells take up glucose (blood sugar), and injected insulin has been an approved, life sustaining treatment for diabetes since 1923, with recombinant human insulin (made by engineered microbes) approved in 1982 and long and rapid acting analogs (modified versions) from 1996 onward. Landmark randomized trials showed that intensive insulin therapy (tight blood sugar control) reduces retinopathy (eye damage), kidney disease, and neuropathy (nerve damage) by 25 to 76% in type 1 diabetes (DCCT) and microvascular complications (damage to small blood vessels) by 25% in type 2 diabetes (UKPDS), at the cost of more hypoglycemia (low blood sugar) and weight gain. It is prescription only in the US except for older human insulins sold over the counter, and it is prohibited by WADA for athletes without a therapeutic use exemption, a documented medical permission to use it.", "mechanism": "Insulin binds the insulin receptor tyrosine kinase on muscle, fat, and liver cells, triggering GLUT4 translocation and glucose uptake, promoting glycogen and fat storage, and suppressing hepatic glucose output and lipolysis. Analogs alter the amino acid sequence or add fatty acid chains to change absorption speed: rapid acting analogs (lispro, aspart, glulisine) act within 15 minutes, while basal analogs (glargine, detemir, degludec) provide flat coverage for 24 hours or longer.", "evidence_grade": "human_rct", "evidence_summary": "Among the strongest evidence bases in medicine. DCCT (n = 1,441, mean 6.5 years) showed intensive insulin therapy in type 1 diabetes reduced the onset of retinopathy by 76%, progression by 54%, microalbuminuria by 39%, and neuropathy by 60%, with a two to three fold increase in severe hypoglycemia. UKPDS 33 (n = 3,867, median 10 years) showed intensive glucose control with sulfonylureas or insulin in type 2 diabetes reduced microvascular endpoints by 25%. ORIGIN (n = 12,537, median 6.2 years) showed basal insulin glargine was neutral for cardiovascular outcomes in people with dysglycemia, with more hypoglycemia and about 1.6 kg weight gain.", "human_evidence": "DCCT 1993: 1,441 patients with type 1 diabetes randomized to intensive (three or more injections or pump, HbA1c about 7%) or conventional therapy (HbA1c about 9%) for a mean 6.5 years; intensive therapy cut retinopathy onset by 76%, retinopathy progression by 54%, microalbuminuria by 39%, and clinical neuropathy by 60%, with severe hypoglycemia about three times more frequent. UKPDS 33 1998: 3,867 newly diagnosed type 2 patients; intensive policy achieved HbA1c 7.0% versus 7.9% and reduced any diabetes related endpoint by 12% and microvascular endpoints by 25%. ORIGIN 2012: 12,537 people with prediabetes or early type 2 diabetes and cardiovascular risk randomized to insulin glargine or standard care for a median 6.2 years; cardiovascular outcomes were neutral (hazard ratio 1.02), severe hypoglycemia rose from 0.31 to 1.00 per 100 person years, and weight rose 1.6 kg.", "animal_evidence": "Insulin was isolated from dog and cattle pancreas in 1921 to 1922 and its glucose lowering effect established in dogs before the first human use in January 1922. Animal studies underpin the physiology; the clinical evidence base is human.", "conditions": [ "type-2-diabetes" ], "literature_dosing": "FDA labels (DailyMed). Humulin R: the dose is individualized to the route, metabolic needs, blood glucose monitoring, and glycemic goal; it is injected subcutaneously about 30 minutes before a meal, generally in a regimen with an intermediate or long acting insulin, or infused intravenously only under medical supervision. Lantus (insulin glargine): injected subcutaneously once daily at the same time each day, with an individualized dose; for adults with type 2 diabetes not already on insulin, the label's recommended starting dose is 0.2 units/kg or up to 10 units once daily. Doses are then adjusted by the prescriber.", "routes": [ "Subcutaneous injection (pens, syringes, vials)", "Continuous subcutaneous infusion (insulin pump)", "Intravenous infusion (hospital use of regular insulin)", "Inhaled powder (Afrezza, rapid acting)" ], "side_effects": [ "Hypoglycemia, including severe events (two to three fold higher with intensive therapy in DCCT)", "Weight gain (about 1.6 kg over 6 years in ORIGIN; more with intensive therapy)", "Lipohypertrophy or lipoatrophy at injection sites", "Injection site reactions", "Hypokalemia with intravenous use or large doses", "Peripheral edema when starting or intensifying", "Allergic reactions (rare)" ], "interactions": [ "Sulfonylureas, meglitinides, GLP-1 agonists, and pramlintide: additive hypoglycemia risk, doses are usually reduced", "Beta blockers: can mask the adrenergic warning signs of hypoglycemia", "Glucocorticoids, thiazides, atypical antipsychotics, and sympathomimetics: raise glucose and insulin requirements", "Thiazolidinediones: increased fluid retention and heart failure risk in combination", "Alcohol: unpredictable effect, often delayed hypoglycemia" ], "contraindications": [ "Hypoglycemia at the time of dosing", "Hypersensitivity to insulin or excipients", "Inhaled insulin: chronic lung disease such as asthma or COPD" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved in many forms: animal derived insulins from 1923, recombinant human insulin (Humulin) in 1982, insulin lispro in 1996, glargine in 2000, and subsequent analogs and biosimilars (which transitioned to biologic regulation in March 2020, enabling interchangeable products such as Semglee). Regular and NPH human insulin are available without a prescription in most states; analogs are prescription only. Insulin is not compounded and is not on any FDA bulks list.", "typical_cost": "Out of pocket cost is capped at 35 USD per month for Medicare Part D beneficiaries since 2023 and by manufacturer programs and several state laws for commercially insured and uninsured patients. List prices for analog insulins were roughly 100 to 300 USD per vial or pen pack before 2024 list price cuts; retailer branded human insulin is about 25 USD per vial. Prices verified on the last verified date.", "access_path": [ "Prescription from a licensed provider filled at a retail pharmacy; some human insulins are sold without a prescription in many states.", "Not available through compounding pharmacies or telehealth peptide clinics as a compounded product." ], "faqs": [ { "q": "Is insulin FDA approved, and what is it used for?", "a": "Yes. Human insulin and insulin analogs (modified versions) are FDA approved to improve glycemic control (blood sugar control) in adults and children with diabetes mellitus, per the Humulin R and Lantus labels; Lantus is not recommended for diabetic ketoacidosis, a dangerous acid buildup from severe insulin shortage. Regular and NPH human insulins (the older, unmodified types) can be bought without a prescription in most states, but analog insulins such as glargine and lispro are prescription only. Since March 2020 insulins are regulated as biologics, drugs made in living cells.", "source_ids": [ "fda-humulin-label", "fda-lantus-label" ] }, { "q": "Does intensive insulin therapy prevent diabetes complications?", "a": "Yes, decisively in type 1 diabetes. In the DCCT, 1,441 patients followed for a mean 6.5 years, intensive therapy reduced new retinopathy by 76%, retinopathy progression by 54%, microalbuminuria by 39%, and neuropathy by 60%. In type 2 diabetes, UKPDS 33 found intensive glucose control cut microvascular complications by 25%. The cost was two to three times more severe hypoglycemia and more weight gain.", "source_ids": [ "dcct-1993", "ukpds-33" ] }, { "q": "What are the side effects of insulin?", "a": "Hypoglycemia is the dominant risk; severe episodes were about three times more frequent with intensive therapy in DCCT and rose from 0.31 to 1.00 per 100 person years in ORIGIN. Weight gain (about 1.6 kg over 6 years in ORIGIN, more with intensive regimens), injection site lipohypertrophy, and edema when starting are common. Allergic reactions are rare.", "source_ids": [ "dcct-1993", "origin-2012" ] }, { "q": "How is the insulin dose set on the FDA label?", "a": "Insulin labels do not give a fixed dose; they direct the prescriber to individualize it from metabolic needs, glucose monitoring, and the glycemic goal. Humulin R is injected about 30 minutes before a meal, usually alongside a longer acting insulin. Lantus is injected once daily at the same time each day, and the label's starting dose for adults with type 2 diabetes new to insulin is 0.2 units/kg or up to 10 units, then titrated.", "source_ids": [ "fda-humulin-label", "fda-lantus-label" ] }, { "q": "How much does insulin cost?", "a": "Far less out of pocket than the list prices suggest. Medicare Part D caps insulin at 35 USD per month since 2023, the three major manufacturers cap most patients at 35 USD through their programs, and several states cap copays. List prices for analogs were roughly 100 to 300 USD per vial or pen pack before 2024 list price cuts, and retailer branded human insulin is about 25 USD per vial. Prices verified on the last verified date.", "source_ids": [ "fda-lantus-label" ] }, { "q": "Is insulin banned by WADA?", "a": "Yes. Insulins and insulin mimetics are prohibited at all times under section S4 (hormone and metabolic modulators) of the WADA Prohibited List because of their anabolic potential. Athletes with diabetes obtain a therapeutic use exemption, which is routinely granted with documentation.", "source_ids": [ "wada-list" ] }, { "q": "Insulin vs GLP-1 drugs for type 2 diabetes: which comes first?", "a": "Current practice favors GLP-1 agonists or tirzepatide before insulin in most type 2 diabetes because they lower HbA1c by 1 to 2 points, cause weight loss rather than gain, rarely cause hypoglycemia, and semaglutide reduces cardiovascular events. Insulin remains essential when HbA1c is very high, in pregnancy, when other drugs fail, and always in type 1 diabetes. The ORIGIN trial showed basal insulin is cardiovascularly neutral, not protective.", "source_ids": [ "origin-2012", "ukpds-33" ] }, { "q": "Does basal insulin cause heart disease or cancer?", "a": "The ORIGIN trial answered this: 12,537 people randomized to insulin glargine or standard care for a median 6.2 years had identical rates of cardiovascular events (hazard ratio 1.02) and no increase in cancer. The trade-offs were more hypoglycemia and about 1.6 kg of weight gain.", "source_ids": [ "origin-2012" ] } ], "studies": [ { "pmid": "8366922", "title": "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (DCCT)", "year": 1993, "design": "Randomized controlled trial, mean 6.5 years", "n": 1441, "population": "Adolescents and adults with type 1 diabetes", "outcome": "Intensive therapy reduced retinopathy onset 76%, progression 54%, microalbuminuria 39%, neuropathy 60%; severe hypoglycemia about three fold higher", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/8366922/" }, { "pmid": "9742976", "title": "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)", "year": 1998, "design": "Randomized controlled trial, median 10 years", "n": 3867, "population": "Newly diagnosed adults with type 2 diabetes", "outcome": "HbA1c 7.0% versus 7.9%; 12% reduction in any diabetes related endpoint and 25% reduction in microvascular endpoints", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9742976/" }, { "pmid": "22686416", "title": "Basal insulin and cardiovascular and other outcomes in dysglycemia (ORIGIN)", "year": 2012, "design": "Randomized, open label cardiovascular outcomes trial, median 6.2 years", "n": 12537, "population": "Adults with prediabetes or early type 2 diabetes and cardiovascular risk factors", "outcome": "Cardiovascular outcomes neutral (hazard ratio 1.02); severe hypoglycemia 1.00 versus 0.31 per 100 person years; weight gain 1.6 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22686416/" } ], "sources": [ { "id": "dcct-1993", "type": "pubmed", "title": "Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993", "url": "https://pubmed.ncbi.nlm.nih.gov/8366922/", "pmid": "8366922", "year": 1993 }, { "id": "ukpds-33", "type": "pubmed", "title": "UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9742976/", "pmid": "9742976", "year": 1998 }, { "id": "origin-2012", "type": "pubmed", "title": "ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22686416/", "pmid": "22686416", "year": 2012 }, { "id": "fda-lantus-label", "type": "fda", "title": "FDA prescribing information for Lantus (insulin glargine) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5e07a0c-7e14-4756-9152-9fea485d654a", "year": 2025 }, { "id": "fda-humulin-label", "type": "fda", "title": "FDA prescribing information for Humulin R (insulin human) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S4 hormone and metabolic modulators (insulins)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "glucagon", "pramlintide", "semaglutide", "tirzepatide" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Insulin (Humulin, Lantus): uses, side effects, and dosing", "description": "Insulin treats type 1 and type 2 diabetes as human insulin and analogs such as Lantus. FDA label uses, how doses are set, side effects, and cost, sourced.", "h1": "Insulin (Humulin, Lantus, and analogs)" } }, { "slug": "glucagon", "name": "Glucagon", "aliases": [ "Glucagon emergency kit", "GlucaGen", "Gvoke", "Baqsimi (nasal glucagon)", "Zegalogue (dasiglucagon)", "Recombinant glucagon" ], "class": "29 amino acid pancreatic peptide hormone (recombinant or synthetic) and the analog dasiglucagon", "one_liner": "FDA approved rescue hormone for severe low blood sugar; injection, nasal powder, autoinjector, and dasiglucagon restore glucose in about 10 to 15 minutes.", "summary": "Glucagon is the pancreatic peptide hormone that raises blood glucose by releasing glycogen (sugar stored in the liver), and injected glucagon has been the FDA approved emergency treatment for severe hypoglycemia (dangerously low blood sugar) in people on insulin for decades. Newer ready to use forms, nasal glucagon (2019), a liquid autoinjector (2019), and the modified version dasiglucagon (2021), match the traditional kit with recovery in roughly 10 to 15 minutes in randomized trials while being far easier to give. It is prescription only and not on the WADA Prohibited List.", "mechanism": "Glucagon activates the glucagon receptor on hepatocytes, stimulating glycogenolysis and gluconeogenesis and raising blood glucose within minutes, provided liver glycogen stores are present. It also relaxes gastrointestinal smooth muscle, which is why it is used as a diagnostic aid in radiology. Dasiglucagon is a 7 amino acid substituted analog that stays stable in solution.", "evidence_grade": "human_rct", "evidence_summary": "Randomized crossover and placebo controlled trials in adults with type 1 diabetes under insulin induced hypoglycemia. Rickels 2016 (n = 75): 3 mg nasal glucagon was non-inferior to 1 mg intramuscular glucagon, with treatment success in 98.7% versus 100%. Pieber 2021 (n = 170): dasiglucagon 0.6 mg restored glucose in a median 10 minutes versus 40 minutes with placebo, with 99% of patients recovered within 15 minutes. Christiansen 2021: a ready to use liquid glucagon autoinjector was non-inferior to the emergency kit with 99 to 100% success. Pieber 2022: a room temperature liquid glucagon was non-inferior to lyophilized glucagon.", "human_evidence": "Rickels 2016: 75 adults with type 1 diabetes had hypoglycemia induced with insulin in a randomized crossover; nasal glucagon 3 mg achieved treatment success (glucose rise to 70 mg/dL or by 20 mg/dL within 30 minutes) in 98.7% versus 100% for 1 mg intramuscular glucagon, with mean time to success 16 versus 13 minutes. Pieber 2021: 170 adults randomized to dasiglucagon 0.6 mg, placebo, or reconstituted glucagon; median time to plasma glucose recovery was 10 minutes with dasiglucagon versus 40 minutes with placebo and 12 minutes with glucagon. Christiansen 2021: two crossover studies found the ready to use liquid glucagon autoinjector non-inferior to the conventional kit with success in 99 to 100% of episodes. Nausea and vomiting were the common effects across trials.", "animal_evidence": "Glucagon was identified as a hyperglycemic pancreatic factor in the 1920s and characterized in dogs and rodents; animal work established its receptor and hepatic actions. The clinical evidence base is human.", "conditions": [ "type-2-diabetes" ], "literature_dosing": "FDA labels (DailyMed). Glucagon for Injection emergency kit, severe hypoglycemia: 1 mg subcutaneously, intramuscularly, or intravenously for adults and children weighing 20 kg or more, and 0.5 mg (or 20 to 30 mcg/kg) under 20 kg, with one repeat dose after 15 minutes if there is no response; the kit is also labeled as a diagnostic aid to slow gut movement during radiologic exams. Gvoke: 1 mg subcutaneously for ages 12 and older and for children 2 to 11 weighing 45 kg or more, 0.5 mg for children 2 to 11 under 45 kg. Baqsimi nasal powder: 3 mg into one nostril for ages 1 and older. Zegalogue (dasiglucagon): 0.6 mg subcutaneously for ages 6 and older. Emergency help is called after every dose, and oral carbohydrates are given once the person responds.", "routes": [ "Subcutaneous or intramuscular injection (kit, prefilled syringe, autoinjector)", "Intranasal powder (3 mg)", "Intravenous (hospital and diagnostic use)" ], "side_effects": [ "Nausea and vomiting (most common, in roughly 20 to 40% in trials)", "Headache", "Injection site pain or nasal discomfort and watery eyes with the nasal form", "Transient increase in heart rate and blood pressure", "Hypersensitivity reactions (rare)", "Rebound hypoglycemia if carbohydrate is not given after recovery" ], "interactions": [ "Beta blockers: transient rise in pulse and blood pressure after glucagon", "Indomethacin: may blunt glucagon's glucose raising effect", "Warfarin: glucagon may increase anticoagulant effect", "Insulin: glucagon is the antidote; both are used in the same patients by design" ], "contraindications": [ "Pheochromocytoma (glucagon can trigger catecholamine release and hypertensive crisis)", "Insulinoma (glucagon can cause rebound hypoglycemia)", "Known hypersensitivity to glucagon or lactose (for lactose containing kits)", "Ineffective in states of depleted liver glycogen such as starvation, adrenal insufficiency, or chronic hypoglycemia (label warning, not a contraindication)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved in multiple forms: glucagon emergency kits (animal derived from 1960 and recombinant from 1998), nasal glucagon (Baqsimi, July 2019), ready to use liquid glucagon autoinjector and prefilled syringe (Gvoke, September 2019), and dasiglucagon (Zegalogue, March 2021), with generic glucagon kits approved from 2020. All are prescription only. Glucagon is not compounded and is not on any FDA bulks list.", "typical_cost": "List prices for a single dose run roughly 100 to 350 USD depending on product, with generic kits at the low end; insurance copays are usually lower and manufacturer savings cards exist. Prices verified on the last verified date.", "access_path": [ "Prescription from a licensed provider filled at a retail pharmacy as an emergency kit, autoinjector, or nasal powder.", "Administered by clinicians in hospitals and emergency settings; not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is glucagon FDA approved, and what is it used for?", "a": "Yes. Glucagon injection kits have been approved for decades, nasal glucagon (Baqsimi) and the liquid autoinjector (Gvoke) were approved in 2019, dasiglucagon (Zegalogue) in 2021, and generic kits from 2020. Their labels cover treatment of severe hypoglycemia (dangerously low blood sugar) in people with diabetes; the kits and Gvoke VialDx are also labeled as a diagnostic aid to temporarily stop gut movement during radiologic (imaging) exams. All are prescription only in the US.", "source_ids": [ "fda-glucagon-label", "fda-baqsimi-label", "fda-gvoke-label", "fda-zegalogue-label" ] }, { "q": "Does nasal glucagon work as well as the injection?", "a": "Yes. In a randomized crossover of 75 adults with type 1 diabetes, 3 mg nasal glucagon reversed insulin induced hypoglycemia in 98.7% of episodes versus 100% for intramuscular glucagon, with a mean time to success of 16 versus 13 minutes. Because it needs no mixing or needle, caregivers use it correctly far more often.", "source_ids": [ "rickels-2016" ] }, { "q": "What are the side effects of glucagon?", "a": "Nausea and vomiting are the main ones, affecting roughly 20 to 40% of people in trials, along with headache and a brief rise in heart rate and blood pressure. Nasal glucagon adds nasal discomfort and watery eyes. Rebound hypoglycemia can occur if the person does not eat after recovering. Serious reactions are rare.", "source_ids": [ "pieber-2021", "fda-glucagon-label" ] }, { "q": "What is the glucagon dose on the FDA label?", "a": "For severe hypoglycemia: the injection kit is 1 mg for adults and children 20 kg or heavier and 0.5 mg under 20 kg; Gvoke is 1 mg from age 12 (and for younger children 45 kg or heavier) and 0.5 mg for children 2 to 11 under 45 kg; Baqsimi is 3 mg into one nostril; Zegalogue is 0.6 mg under the skin. If there is no response after 15 minutes, one more dose can be given while waiting for emergency help, and oral carbohydrates follow once the person can swallow.", "source_ids": [ "fda-glucagon-label", "fda-gvoke-label", "fda-baqsimi-label", "fda-zegalogue-label" ] }, { "q": "How much does glucagon cost?", "a": "A single dose lists at roughly 100 to 350 USD depending on the product, with generic kits at the low end and the newer ready to use forms at the high end. Insurance copays are usually much lower and manufacturers offer savings cards. Prices verified on the last verified date and change.", "source_ids": [ "fda-glucagon-label" ] }, { "q": "Is glucagon banned by WADA?", "a": "No. Glucagon is not on the WADA Prohibited List. Athletes with diabetes can carry and use it freely, unlike insulin, which requires a therapeutic use exemption.", "source_ids": [ "wada-list" ] }, { "q": "Glucagon vs dasiglucagon: what is the difference?", "a": "Dasiglucagon is a glucagon analog with seven amino acid substitutions that keeps it stable in solution, so it comes as a ready to use autoinjector without mixing. In a 170 person randomized trial it restored glucose in a median 10 minutes versus 12 minutes for reconstituted glucagon and 40 minutes for placebo, with 99% recovered within 15 minutes. Efficacy is equivalent; convenience is the difference.", "source_ids": [ "pieber-2021" ] }, { "q": "Is glucagon used for weight loss?", "a": "Not on its own. Glucagon raises energy expenditure and reduces appetite in physiology studies, which is why glucagon receptor agonism is built into the investigational weight loss peptides retatrutide, survodutide, and mazdutide. Injected glucagon itself is a short acting rescue drug and is not a weight loss treatment.", "source_ids": [ "fda-glucagon-label" ] } ], "studies": [ { "pmid": "26681725", "title": "Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study", "year": 2016, "design": "Randomized crossover non-inferiority trial", "n": 75, "population": "Adults with type 1 diabetes with insulin induced hypoglycemia", "outcome": "Treatment success 98.7% with 3 mg nasal glucagon versus 100% with 1 mg intramuscular glucagon; mean time to success 16 versus 13 minutes", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26681725/" }, { "pmid": "35239971", "title": "Dasiglucagon, a next-generation glucagon analog for rapid and effective treatment of severe hypoglycemia: results of phase 3 randomized double-blind clinical trial", "year": 2021, "design": "Randomized, double blind, placebo controlled phase 3 trial", "n": 170, "population": "Adults with type 1 diabetes with insulin induced hypoglycemia", "outcome": "Median time to glucose recovery 10 minutes with dasiglucagon versus 40 minutes with placebo; 99% recovered within 15 minutes", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/35239971/" }, { "pmid": "34620618", "title": "Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies", "year": 2021, "design": "Two randomized crossover non-inferiority studies", "population": "Adults with type 1 diabetes with insulin induced hypoglycemia", "outcome": "Liquid glucagon autoinjector non-inferior to the emergency kit with 99 to 100% treatment success", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34620618/" }, { "pmid": "35322535", "title": "Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for insulin-induced severe hypoglycaemia in adults with type 1 diabetes", "year": 2022, "design": "Randomized crossover non-inferiority phase 3 trial", "population": "Adults with type 1 diabetes with insulin induced hypoglycemia", "outcome": "Room temperature liquid glucagon non-inferior to lyophilized glucagon for glucose recovery and symptom relief", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/35322535/" } ], "sources": [ { "id": "rickels-2016", "type": "pubmed", "title": "Rickels MR et al. Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: a randomized crossover noninferiority study. Diabetes Care 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26681725/", "pmid": "26681725", "year": 2016 }, { "id": "pieber-2021", "type": "pubmed", "title": "Pieber TR et al. Dasiglucagon, a next-generation glucagon analog for rapid and effective treatment of severe hypoglycemia: phase 3 randomized double-blind clinical trial. Diabetes Care 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/35239971/", "pmid": "35239971", "year": 2021 }, { "id": "christiansen-2021", "type": "pubmed", "title": "Christiansen MP et al. Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for severe hypoglycemia: two randomized crossover non-inferiority studies. BMJ Open Diabetes Res Care 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34620618/", "pmid": "34620618", "year": 2021 }, { "id": "pieber-2022", "type": "pubmed", "title": "Pieber TR et al. Phase 3 noninferiority study of ready-to-use room temperature liquid glucagon versus lyophilised glucagon for insulin-induced severe hypoglycaemia. Diabetes Obes Metab 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35322535/", "pmid": "35322535", "year": 2022 }, { "id": "fda-glucagon-label", "type": "fda", "title": "FDA prescribing information for Glucagon for Injection emergency kit, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8cc40354-b5ac-45b6-a211-93b44444f2a3", "year": 2026 }, { "id": "fda-baqsimi-label", "type": "fda", "title": "FDA prescribing information for Baqsimi (glucagon) nasal powder, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1f5df9b-872f-44e5-a18f-f0b68e7e9254", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-gvoke-label", "type": "fda", "title": "FDA prescribing information for Gvoke (glucagon) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92385737-dbad-98c5-e053-2995a90a2805", "year": 2026 }, { "id": "fda-zegalogue-label", "type": "fda", "title": "FDA prescribing information for Zegalogue (dasiglucagon) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14704879-872c-4967-8779-04a3bbdfb4e6", "year": 2026 } ], "related": [ "insulin", "pramlintide", "retatrutide", "survodutide" ], "cluster": "metabolic", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Glucagon (Gvoke, Baqsimi): uses, side effects, and dosing", "description": "Glucagon treats severe low blood sugar as an injection kit, Gvoke, or Baqsimi nasal powder. FDA label uses and doses, side effects, and dasiglucagon.", "h1": "Glucagon (Gvoke, Baqsimi, and glucagon kits)" } }, { "slug": "thymosin-alpha-1", "name": "Thymosin alpha-1", "aliases": [ "Thymalfasin", "Zadaxin", "Ta1", "T-alpha-1", "Thymosin alpha 1 acetate" ], "class": "28 amino acid N-acetylated thymic peptide (synthetic form of a natural thymus derived immunomodulator)", "one_liner": "Immune modulating thymus peptide approved abroad (not the US) for hepatitis B and as a vaccine booster; mixed sepsis trials; FDA nomination withdrawn.", "summary": "Thymosin alpha-1 (thymalfasin) is a synthetic copy of a 28 amino acid peptide from the thymus, the gland where immune T cells mature, that enhances T cell maturation and function. It is approved as Zadaxin in more than 30 countries, mainly in Asia and Europe, for chronic hepatitis B and as an immune adjuvant (a helper that strengthens immune responses, such as to vaccines), but it has never been approved by FDA. A randomized trial in chronic hepatitis B showed a higher rate of viral clearance at 18 months (41% versus 9%), while the largest sepsis trial (361 patients) found a mortality reduction that was not statistically significant, meaning it could have been chance. FDA placed it in 503A Category 2 (compounding ingredients flagged for significant safety risks) in 2023; the nomination has since been withdrawn, leaving no lawful US compounding pathway.", "mechanism": "Thymosin alpha-1 acts on toll-like receptors (TLR2 and TLR9) on dendritic cells and precursor T cells, promoting T cell differentiation, increasing IL-2 and interferon production, enhancing natural killer and CD8 cytotoxic activity, and reducing T cell exhaustion markers. It has no direct antiviral or antibacterial action; its effects come from immune restoration, which is why it has been studied in hepatitis, sepsis, and severe COVID-19.", "evidence_grade": "human_rct", "evidence_summary": "Randomized trials exist but results are mixed and mostly from Asia. Chien 1998 (n = 98, chronic hepatitis B): 1.6 mg subcutaneously twice weekly for 26 weeks produced complete virological response in 40.6% versus 9.4% of untreated controls at 18 months, with histological improvement and no significant side effects. Wu 2013 ETASS (n = 361, severe sepsis): 28 day mortality was 26.0% with thymosin alpha-1 versus 35.0% with control, a relative risk of 0.74 that did not reach conventional significance (p = 0.062). Liu 2020 (n = 76, severe COVID-19, retrospective): mortality 11.1% versus 30.0% in treated versus untreated patients. Reviews by Camerini 2015 and Dominari 2020 summarize decades of use as an adjuvant with a consistently benign safety profile.", "human_evidence": "Chien 1998: 98 patients with chronic hepatitis B randomized to 26 weeks of therapy, 52 weeks of therapy, or no treatment; complete clearance of HBV DNA and HBeAg at 18 months occurred in 40.6%, 26.5%, and 9.4% respectively, and responses accumulated after therapy ended. Wu 2013: 361 ICU patients with severe sepsis in six Chinese hospitals randomized to thymosin alpha-1 1.6 mg twice daily for 7 days plus standard care or standard care alone; 28 day mortality 26.0% versus 35.0% (relative risk 0.74, 95% CI 0.54 to 1.02) with greater recovery of monocyte HLA-DR expression. Liu 2020: retrospective review of 76 severe COVID-19 cases in Wuhan; treated patients had 11.1% mortality versus 30.0%, with restoration of CD4 and CD8 counts and reduced PD-1 and Tim-3 exhaustion markers. Camerini 2015 and Dominari 2020 review roughly four decades of trials in hepatitis B and C, as a vaccine adjuvant in dialysis patients, and in cancer immunotherapy, noting consistent tolerability.", "animal_evidence": "Mouse and rat studies show thymosin alpha-1 restores T cell function after thymectomy, chemotherapy, or immunosuppression, improves survival in bacterial and fungal infection models, and acts through TLR signaling on dendritic cells. Animal data established the mechanism; the evidence base is human.", "conditions": [ "inflammation" ], "literature_dosing": "Chronic hepatitis B (Chien 1998 and Zadaxin labeling abroad): 1.6 mg subcutaneously twice weekly for 6 to 12 months. Severe sepsis (Wu 2013): 1.6 mg subcutaneously twice daily for 7 days. Vaccine adjuvant studies: 1.6 mg twice weekly around vaccination. These are trial and foreign label doses; there is no US label.", "routes": [ "Subcutaneous injection (all trials and foreign labeling)" ], "side_effects": [ "Injection site redness and discomfort (most common)", "Transient muscle aches or flu like symptoms", "No significant side effects in the hepatitis B trial and no serious drug related events in the sepsis trial", "Immunogenicity risk from impurities in compounded product (FDA Category 2 rationale)" ], "interactions": [ "Immunosuppressants (corticosteroids, calcineurin inhibitors, biologics): thymosin alpha-1 aims to increase immune activity and could oppose them; no formal interaction studies", "Interferon alfa: combined regimens have been studied in hepatitis and appear tolerable", "Vaccines: used deliberately as an adjuvant to improve responses in immunocompromised patients" ], "contraindications": [ "Deliberate immunosuppression, such as after organ transplant (theoretical, from mechanism)", "Known hypersensitivity", "Pregnancy and breastfeeding (no data)", "Autoimmune disease has not been studied and warrants caution" ], "wada_status": "unclear", "fda_status": "category_2_removed", "compounding_status": "Not FDA approved, although approved as Zadaxin (thymalfasin) in more than 30 countries. FDA placed thymosin alpha-1 in 503A Category 2 in 2023, citing immunogenicity risk and inadequate safety information for compounded product. FDA's Category 2 page (current as of April 22, 2026) now lists it under bulk drug substances nominated but withdrawn, so it is no longer in Category 2 but has no active nomination and is not on the 503A bulks list. That leaves US compounding pharmacies without a lawful basis to make it. It was not among the peptides reviewed by the advisory committee in July 2026.", "typical_cost": "Not available through licensed US channels since the 2023 Category 2 placement. Zadaxin is sold by prescription in countries where it is approved.", "access_path": [ "No lawful United States access path identified on the last verified date; the 503A nomination was withdrawn and it is not on the bulks list.", "Not available as an FDA approved product in the United States, although approved abroad as Zadaxin (thymalfasin).", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is thymosin alpha-1 legal in the United States?", "a": "It is not FDA approved and cannot currently be compounded lawfully. FDA placed it in 503A Category 2 (compounding ingredients flagged for significant safety risks) in 2023; the nomination was later withdrawn, which removes it from Category 2 but also leaves it off the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients), so pharmacies have no lawful basis to compound it. It is a prescription drug (Zadaxin) in more than 30 other countries. Possession is not a crime; research chemical products are not for human use.", "source_ids": [ "fda-category-2", "fda-503a-bulks", "camerini-2015" ] }, { "q": "Does thymosin alpha-1 work for hepatitis B?", "a": "In a 98 patient randomized trial, a 26 week course of 1.6 mg twice weekly produced complete virological response (loss of HBV DNA and HBeAg) in 40.6% of patients versus 9.4% of untreated controls when assessed at 18 months, with histological improvement and no significant side effects. That is the basis of its approval abroad. It is now rarely used in the West because nucleoside antivirals are more effective and oral.", "source_ids": [ "chien-1998", "camerini-2015" ] }, { "q": "Does thymosin alpha-1 help sepsis or severe infections?", "a": "Possibly, but not proven. In the 361 patient ETASS trial, 28 day mortality in severe sepsis was 26.0% with thymosin alpha-1 versus 35.0% with standard care, a relative risk of 0.74 that missed statistical significance (p = 0.062). A retrospective study of 76 severe COVID-19 patients found lower mortality (11.1% versus 30.0%) in treated patients, but retrospective data cannot establish cause. Larger confirmatory trials are needed.", "source_ids": [ "wu-2013", "liu-2020" ] }, { "q": "What are the side effects of thymosin alpha-1?", "a": "Few. Injection site redness and discomfort are the most common, with occasional transient muscle aches. The hepatitis B trial reported no significant side effects and the sepsis trial no serious drug related events. FDA's Category 2 concern was about immunogenicity and impurities in compounded product rather than the molecule's clinical record.", "source_ids": [ "chien-1998", "wu-2013", "fda-category-2" ] }, { "q": "How is thymosin alpha-1 taken?", "a": "By subcutaneous injection. Hepatitis B regimens use 1.6 mg twice weekly for 6 to 12 months, the sepsis trial used 1.6 mg twice daily for 7 days, and vaccine adjuvant studies used 1.6 mg twice weekly around vaccination. These are trial and foreign label doses; there is no US label.", "source_ids": [ "chien-1998", "wu-2013", "dominari-2020" ] }, { "q": "How much does thymosin alpha-1 cost?", "a": "It is not currently available through licensed US channels. Zadaxin is available by prescription in countries where it is approved.", "source_ids": [ "fda-category-2" ] }, { "q": "Is thymosin alpha-1 banned by WADA?", "a": "It is not named on the WADA Prohibited List. Because it is approved by health authorities in many countries, the S0 non-approved substance rule does not clearly apply, and it is not a growth factor or hormone in the S2 sense. PeptideAgent marks it unclear; athletes should ask their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "Thymosin alpha-1 vs TB-500 (thymosin beta-4): what is the difference?", "a": "They share a name and nothing else. Thymosin alpha-1 is an immune modulator with decades of human trials and approvals abroad. TB-500 is a fragment of thymosin beta-4, a cell migration protein studied for tissue repair, with no human RCT data. TB-500 was recommended for the 503A bulks list by FDA's advisory committee in July 2026; thymosin alpha-1 was not reviewed.", "source_ids": [ "dominari-2020", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "9581695", "title": "Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial", "year": 1998, "design": "Randomized controlled trial with untreated control, 18 month follow up", "n": 98, "population": "Adults with chronic hepatitis B in Taiwan", "outcome": "Complete virological response at 18 months in 40.6% (26 week course) and 26.5% (52 week course) versus 9.4% of controls; histological improvement; no significant side effects", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9581695/" }, { "pmid": "23327199", "title": "The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial", "year": 2013, "design": "Multicenter, single blind, randomized controlled trial", "n": 361, "population": "ICU patients with severe sepsis in China", "outcome": "28 day mortality 26.0% versus 35.0% (relative risk 0.74, 95% CI 0.54 to 1.02, p = 0.062); improved monocyte HLA-DR recovery", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23327199/" }, { "pmid": "32442287", "title": "Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells", "year": 2020, "design": "Retrospective cohort", "n": 76, "population": "Patients with severe COVID-19 in Wuhan", "outcome": "Mortality 11.1% in treated versus 30.0% in untreated patients; restored T cell counts and reduced exhaustion markers", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/32442287/" }, { "pmid": "26098768", "title": "Historical review of thymosin alpha 1 in infectious diseases", "year": 2015, "design": "Narrative review", "population": "Trials in hepatitis B and C, vaccine adjuvant use, and other infections", "outcome": "Summarizes decades of clinical use and approvals in more than 30 countries with a benign safety profile", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26098768/" }, { "pmid": "33362999", "title": "Thymosin alpha 1: A comprehensive review of the literature", "year": 2020, "design": "Narrative review", "population": "Human and preclinical studies across infection, cancer, and immunodeficiency", "outcome": "Summarizes mechanism, dosing regimens, and clinical evidence across indications", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33362999/" } ], "sources": [ { "id": "chien-1998", "type": "pubmed", "title": "Chien RN et al. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9581695/", "pmid": "9581695", "year": 1998 }, { "id": "wu-2013", "type": "pubmed", "title": "Wu J et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care 2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23327199/", "pmid": "23327199", "year": 2013 }, { "id": "liu-2020", "type": "pubmed", "title": "Liu Y et al. Thymosin alpha 1 reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32442287/", "pmid": "32442287", "year": 2020 }, { "id": "camerini-2015", "type": "pubmed", "title": "Camerini R, Garaci E. Historical review of thymosin alpha 1 in infectious diseases. Expert Opin Biol Ther 2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26098768/", "pmid": "26098768", "year": 2015 }, { "id": "dominari-2020", "type": "pubmed", "title": "Dominari A et al. Thymosin alpha 1: A comprehensive review of the literature. World J Virol 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33362999/", "pmid": "33362999", "year": 2020 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list and withdrawn nominations, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA: July 23-24, 2026 meeting of the Pharmacy Compounding Advisory Committee (BPC-157, KPV, TB-500, MOTS-c, DSIP, semax, epitalon)", "url": "https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "thymulin", "thymalin", "tb-500", "ll-37" ], "cluster": "immune", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "thymulin", "name": "Thymulin", "aliases": [ "Facteur thymique serique (FTS)", "Serum thymic factor", "FTS-Zn", "Nonathymulin", "Thymic nonapeptide", "pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn" ], "class": "Zinc dependent nonapeptide (9 amino acids) hormone produced by thymic epithelial cells", "one_liner": "Zinc dependent thymus hormone (9 amino acids) with 1980s rheumatoid arthritis trials and rodent anti-inflammatory data; never approved, never nominated to FDA.", "summary": "Thymulin is a nine amino acid hormone made by the thymus, the gland where immune T cells mature, that requires zinc to be biologically active and helps T cells mature. Its clinical record is thin and old: two small double blind trials (neither patients nor doctors knew who got the drug) published in 1987 found a synthetic form (nonathymulin) at 5 mg daily improved rheumatoid arthritis in 56% of patients versus 17% on placebo, but development stopped and no modern trial exists, while more recent rodent work shows analgesic (pain relieving) and anti-inflammatory effects. It is not approved anywhere, has never been nominated for FDA's compounding lists, and falls under WADA's S0 prohibition on unapproved substances.", "mechanism": "Thymulin binds zinc in a one to one complex, and only the zinc bound form is active. It promotes differentiation of T cell precursors, modulates T cell subsets and natural killer activity, and is regulated by pituitary hormones such as growth hormone and prolactin, so it is considered part of a thymus to neuroendocrine axis. Rodent studies show it reduces pro-inflammatory cytokines and pain behaviors, possibly through effects on glial and immune cells.", "evidence_grade": "human_rct", "evidence_summary": "Human evidence comes from two double blind placebo controlled trials in rheumatoid arthritis reported together in 1987 (Amor et al.), which compared nonathymulin 1, 5, and 10 mg daily and found the 5 mg dose produced clinical improvement by global assessment in 56% of patients versus 17% on placebo with minimal adverse effects. The work was not replicated and no trial has been published since. Preclinical work by Dardenne, Bach, and later groups characterized the zinc dependence and, in rodents, anti-inflammatory and analgesic effects of thymulin and a synthetic analog. PeptideAgent grades the evidence human RCT on the strength of the 1987 trials but notes they are small, old, and unconfirmed.", "human_evidence": "Amor 1987: two randomized double blind placebo controlled trials in rheumatoid arthritis compared nonathymulin at 1, 5, and 10 mg per day; the 5 mg dose gave significant clinical improvement (56% of all entered patients improved by global assessment versus 17% on placebo, p below 0.02) and improvement in four objective measures, with minimal side effects and no clear change in immune parameters. No subsequent controlled trial of thymulin in any condition has been indexed. Circulating thymulin levels have been measured as a marker of thymic function in aging, zinc deficiency, and malnutrition, which is observational, not therapeutic, evidence.", "animal_evidence": "Dardenne 1982 (PNAS) showed that zinc and certain other metals are required for the biological activity of serum thymic factor, defining thymulin as a metallopeptide. Reggiani 2014 reviews rodent studies in which thymulin or its analog reduced inflammation and pain and in which thymulin gene therapy corrected hormonal abnormalities in athymic (nude) mice. Safieh-Garabedian 2019 reviews rodent neuropathic pain models in which a thymulin related peptide reduced hyperalgesia and inflammatory mediators.", "conditions": [ "inflammation" ], "literature_dosing": "Rheumatoid arthritis trials (Amor 1987): nonathymulin 1, 5, or 10 mg per day, with 5 mg identified as most effective. No dosing has been established for any other use, and no modern human dose finding study exists.", "routes": [ "Injection (1987 trials)", "Subcutaneous injection and intranasal (as sold, not from published trials)" ], "side_effects": [ "Minimal adverse effects reported in the 1987 rheumatoid arthritis trials", "No modern human safety data", "Injection site reactions reported anecdotally", "Immunogenicity risk from impurities in unregulated products" ], "interactions": [ "No human interaction data exist", "Zinc status affects activity, so zinc supplements or deficiency could change effect (mechanistic, not clinical, evidence)", "Immunosuppressants: theoretical opposition of effect" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "Autoimmune disease outside the studied rheumatoid arthritis setting (no data)", "Athletes subject to WADA testing (prohibited at all times under S0)", "Any use requiring an approved product: none exists" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Not FDA approved and not approved in any country. Thymulin does not appear on the FDA 503A bulks list, in Category 2, or among the withdrawn nominations as of the FDA pages current to April 2026, and it has no USP monograph, so there is no lawful basis for a US compounding pharmacy to dispense it. It was not part of the July 2026 advisory committee review. Products sold online are research chemicals.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "No lawful United States access path identified on the last verified date.", "Not available as an FDA approved product, not nominated for the 503A bulks list, and not eligible for compounding under section 503A or 503B.", "Products labeled research use only are not lawful for human use and are not verified for identity or purity." ], "faqs": [ { "q": "Is thymulin legal in the United States?", "a": "It is not FDA approved, has never been nominated for the 503A bulks list (FDA's list of raw ingredients pharmacies may use to compound drugs for individual patients), and has no USP monograph (an official drug quality standard), so no pharmacy can lawfully compound it. It has not been through FDA's Category 2 review (FDA's safety screen of nominated compounding ingredients) because nobody has nominated it. Possession is not a crime, but research chemical products are not for human use.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Does thymulin work for inflammation or autoimmune disease?", "a": "The only human evidence is two small double blind trials in rheumatoid arthritis published in 1987, in which 5 mg daily of synthetic thymulin (nonathymulin) improved 56% of patients versus 17% on placebo. That result was never replicated and development stopped. Rodent studies since then show reduced inflammation and pain, but nothing has been tested in modern human trials.", "source_ids": [ "amor-1987", "reggiani-2014" ] }, { "q": "What are the side effects of thymulin?", "a": "Largely unknown. The 1987 rheumatoid arthritis trials reported minimal adverse effects, and there are no modern human safety data. Injection site reactions are reported anecdotally. Because products are unregulated, impurity and immunogenicity risk is a practical concern.", "source_ids": [ "amor-1987" ] }, { "q": "How is thymulin taken?", "a": "The 1987 trials used 1, 5, or 10 mg of nonathymulin per day by injection, with 5 mg the most effective. Products sold online are subcutaneous or intranasal preparations with no published human dose. Activity depends on zinc binding, which is another reason unregulated products are unpredictable.", "source_ids": [ "amor-1987", "dardenne-1982" ] }, { "q": "How much does thymulin cost?", "a": "There is no licensed price. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is thymulin banned by WADA?", "a": "It is not named, but section S0 of the WADA Prohibited List prohibits at all times any pharmacological substance with no current approval by a governmental health authority for human use. Thymulin has no approval anywhere, so it falls under S0.", "source_ids": [ "wada-list" ] }, { "q": "Thymulin vs thymosin alpha-1: what is the difference?", "a": "Both are thymus derived immune peptides, but their evidence differs sharply. Thymosin alpha-1 (28 amino acids) has decades of randomized trials in hepatitis B and sepsis and is approved in more than 30 countries. Thymulin (9 amino acids, zinc dependent) has two 1987 rheumatoid arthritis trials and rodent data, with no approval anywhere. Thymulin is also distinct from thymalin, a crude thymus extract used in Russia.", "source_ids": [ "reggiani-2014", "amor-1987" ] }, { "q": "Why does thymulin need zinc?", "a": "The peptide is inactive on its own. A 1982 study showed that zinc, and to a lesser extent a few other metals, must bind the peptide for it to have biological activity on T cells, which is why it is sometimes sold as FTS-Zn. Low thymulin activity in zinc deficiency and malnutrition is one of the ways this was discovered.", "source_ids": [ "dardenne-1982", "bach-1989" ] } ], "studies": [ { "pmid": "3310925", "title": "Nonathymulin in rheumatoid arthritis: two double blind, placebo controlled trials", "year": 1987, "design": "Two randomized, double blind, placebo controlled trials comparing 1, 5, and 10 mg per day", "population": "Adults with rheumatoid arthritis", "outcome": "5 mg per day improved 56% of patients by global assessment versus 17% on placebo (p below 0.02), with minimal adverse effects", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/3310925/" }, { "pmid": "6957870", "title": "Contribution of zinc and other metals to the biological activity of the serum thymic factor", "year": 1982, "design": "In vitro and in vivo biochemical study", "population": "Purified serum thymic factor and rodent T cell assays", "outcome": "Zinc binding is required for biological activity, defining thymulin as a metallopeptide", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/6957870/" }, { "pmid": "24588820", "title": "Physiology and therapeutic potential of the thymic peptide thymulin", "year": 2014, "design": "Narrative review", "population": "Rodent and human physiology studies, thymulin gene therapy in athymic mice", "outcome": "Summarizes neuroendocrine regulation, anti-inflammatory and analgesic effects in rodents, and gene therapy results in nude mice", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/24588820/" }, { "pmid": "30503917", "title": "Targeting inflammatory components in neuropathic pain: The analgesic effect of thymulin related peptide", "year": 2019, "design": "Review of rodent neuropathic pain studies", "population": "Rodent models of inflammatory and neuropathic pain", "outcome": "A thymulin related peptide reduced hyperalgesia and inflammatory mediators in rodents", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/30503917/" } ], "sources": [ { "id": "amor-1987", "type": "pubmed", "title": "Amor B et al. Nonathymulin in rheumatoid arthritis: two double blind, placebo controlled trials. Ann Rheum Dis 1987", "url": "https://pubmed.ncbi.nlm.nih.gov/3310925/", "pmid": "3310925", "year": 1987 }, { "id": "dardenne-1982", "type": "pubmed", "title": "Dardenne M et al. Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci USA 1982", "url": "https://pubmed.ncbi.nlm.nih.gov/6957870/", "pmid": "6957870", "year": 1982 }, { "id": "bach-1989", "type": "pubmed", "title": "Bach JF, Dardenne M. Thymulin, a zinc-dependent hormone. Med Oncol Tumor Pharmacother 1989", "url": "https://pubmed.ncbi.nlm.nih.gov/2657247/", "pmid": "2657247", "year": 1989 }, { "id": "reggiani-2014", "type": "pubmed", "title": "Reggiani PC et al. Physiology and therapeutic potential of the thymic peptide thymulin. Curr Pharm Des 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24588820/", "pmid": "24588820", "year": 2014 }, { "id": "safieh-garabedian-2019", "type": "pubmed", "title": "Safieh-Garabedian B et al. Targeting inflammatory components in neuropathic pain: the analgesic effect of thymulin related peptide. Neurosci Lett 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30503917/", "pmid": "30503917", "year": 2019 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-category-2", "type": "fda", "title": "FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2 list, content current as of April 22, 2026)", "url": "https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "thymosin-alpha-1", "thymalin", "tb-500", "epitalon" ], "cluster": "immune", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "ll-37", "name": "LL-37", "aliases": [ "Cathelicidin LL-37", "hCAP18 C-terminal peptide", "Human cathelicidin antimicrobial peptide", "Ropocamptide", "CAP-18" ], "class": "Human cathelicidin antimicrobial peptide (37 amino acids, cleaved from the hCAP18 precursor)", "one_liner": "The only human cathelicidin, a germ-killing peptide. A skin gel had two small leg ulcer RCTs; no human data for injections. Off FDA Category 2 since April 2026.", "summary": "LL-37 is the 37 amino acid antimicrobial (germ-killing) peptide that human neutrophils (a type of white blood cell) and skin cells release from the hCAP18 protein. The only human trials are of a gel applied to hard to heal venous leg ulcers (sores caused by poor vein circulation): a 34 patient phase I/II trial (an early stage study) found faster healing at two of three doses, and a larger phase IIb trial did not meet its primary endpoint, its main goal, in the full population. It is not FDA approved for any use; FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) on April 15, 2026, and it has not been added to the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients).", "mechanism": "LL-37 is amphipathic and cationic. It disrupts bacterial membranes, neutralizes lipopolysaccharide, and acts as a chemoattractant for neutrophils, monocytes, and T cells through the formyl peptide receptor FPR2. In wound models it stimulates keratinocyte migration, angiogenesis, and re-epithelialization, and it modulates toll-like receptor signaling. High concentrations are cytotoxic to human cells, which is why the topical wound trials tested a narrow dose range.", "evidence_grade": "human_rct", "evidence_summary": "Two randomized placebo controlled trials of topical LL-37 in venous leg ulcers exist. The phase I/II trial (n = 34) found the 0.5 mg/mL and 1.6 mg/mL gels healed ulcers faster than placebo, while 3.2 mg/mL did not. The larger phase IIb trial did not meet its primary endpoint across all patients and reported a signal only in a subgroup with larger ulcers. There are no human trials of injected or systemic LL-37, which is the form sold online.", "human_evidence": "Gronberg 2014: 34 adults with hard to heal venous leg ulcers randomized to placebo or LL-37 gel at 0.5, 1.6, or 3.2 mg/mL twice weekly for 4 weeks. The two lower doses produced significantly faster healing rates than placebo with no dose limiting toxicity; the highest dose was not better than placebo. Mahlapuu 2021: a multicenter phase IIb trial of the two lower doses in venous leg ulcers that did not reach its primary endpoint in the whole study population. No human data exist for subcutaneous injection, nebulized, or oral LL-37.", "animal_evidence": "In mice and rats, LL-37 applied to wounds or delivered by gene transfer accelerated re-epithelialization and angiogenesis, and LL-37 or its analogs protected against bacterial infection in skin, lung, and sepsis models. Rodent work also shows pro inflammatory and cytotoxic effects at higher concentrations, and LL-37 is elevated in psoriasis and rosacea lesions, where it is thought to drive inflammation rather than resolve it.", "conditions": [ "wound-healing" ], "literature_dosing": "Topical gel at 0.5 mg/mL or 1.6 mg/mL applied to the ulcer twice weekly for 4 weeks (Gronberg 2014; the same two concentrations were used in Mahlapuu 2021). No human dose exists for injected or systemic LL-37.", "routes": [ "Topical gel on chronic wounds (clinical trials)", "Subcutaneous injection (as sold, no human data)", "Nebulized or intranasal (as sold, no human data)" ], "side_effects": [ "Topical trials: local wound reactions comparable to placebo at the two lower doses; the 3.2 mg/mL dose was not better than placebo and higher concentrations are cytotoxic in vitro", "No systemic human safety data for injected LL-37", "Theoretical concern that LL-37 worsens autoimmune and inflammatory skin disease, because it is elevated in psoriasis and rosacea lesions", "Injection site pain and flu like symptoms reported anecdotally" ], "interactions": [ "No human interaction studies exist", "In vitro, LL-37 binds and neutralizes lipopolysaccharide and can complex with self DNA and RNA to activate plasmacytoid dendritic cells, which is the proposed mechanism in psoriasis; relevance to co-administered drugs is unknown" ], "contraindications": [ "Psoriasis, rosacea, or lupus (theoretical, LL-37 is implicated in these diseases)", "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited under S0)" ], "wada_status": "prohibited", "fda_status": "category_2_removed", "compounding_status": "Not an FDA approved drug. LL-37 was placed on the FDA 503A Category 2 list (bulk substances with significant safety risks) in 2023 and was one of the peptides FDA now lists as withdrawn from 503A Category 2 (page current as of April 22, 2026) after the nominations were withdrawn. It was not among the peptides the Pharmacy Compounding Advisory Committee recommended for the 503A bulks list at its July 23 to 24, 2026 meeting, so it currently sits in neither category and most 503A pharmacies will not compound it. Not eligible for 503B outsourcing.", "typical_cost": "Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. Not routinely available through licensed telehealth or compounding channels as of the last verified date.", "access_path": [ "Not available as an FDA approved product.", "It is off Category 2 but not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is LL-37 legal in the United States?", "a": "It is not an FDA approved drug. FDA removed LL-37 from its 503A Category 2 list on April 15, 2026, which lifted the significant safety risk designation, but it was not among the peptides the July 2026 advisory committee (FDA's outside expert panel) recommended for the 503A bulks list, the list of ingredients pharmacies may use to compound drugs for individual patients. That leaves it in a gray zone where most compounding pharmacies will not fill it. Buying it as a research chemical for personal use is not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does LL-37 work for wound healing?", "a": "Topically, maybe. In a 34 patient randomized trial, LL-37 gel at 0.5 and 1.6 mg/mL healed venous leg ulcers faster than placebo over 4 weeks. A larger phase IIb trial of the same doses did not meet its primary endpoint in the full population. No trial has tested the injected form people buy online, so there is no evidence it heals anything when injected.", "source_ids": [ "gronberg-2014", "mahlapuu-2021" ] }, { "q": "Does LL-37 fight infections in people?", "a": "Not demonstrated. LL-37 kills bacteria in the test tube and protects mice from infection, but no human trial has tested it as an antibiotic. Its antimicrobial activity in vitro is reduced by physiological salt and serum, which is one reason clinical development has focused on wounds rather than systemic infection.", "source_ids": [ "vandamme-2012" ] }, { "q": "What are the side effects of LL-37?", "a": "In the topical trials, local effects at the two lower doses were similar to placebo, and the highest dose (3.2 mg/mL) lost its benefit, consistent with LL-37 being toxic to human cells at higher concentrations. There is no systemic safety data. LL-37 is overproduced in psoriasis and rosacea lesions and is thought to drive inflammation there, so people with those conditions have a theoretical reason to avoid it.", "source_ids": [ "gronberg-2014", "vandamme-2012" ] }, { "q": "How is LL-37 taken?", "a": "In the clinical trials it was a gel applied to the ulcer twice a week for 4 weeks. Products sold online are usually lyophilized vials for subcutaneous injection, sometimes nebulized. No human study has used those routes, so no dose exists for them.", "source_ids": [ "gronberg-2014", "mahlapuu-2021" ] }, { "q": "How much does LL-37 cost?", "a": "Products sold as research chemicals are not lawful for human use and are not tested for purity. It is not routinely offered by licensed telehealth or compounding channels.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is LL-37 banned by WADA?", "a": "Yes. LL-37 has no approval from any government health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times.", "source_ids": [ "wada-list" ] }, { "q": "LL-37 vs thymosin alpha-1 for immune support: which has better evidence?", "a": "Thymosin alpha-1 is an approved drug in several countries and has randomized human trials in hepatitis B and as a vaccine adjuvant. LL-37 has only two topical wound trials and no systemic human data. Neither is FDA approved, and neither has evidence for general immune support in healthy people.", "source_ids": [ "gronberg-2014", "vandamme-2012" ] } ], "studies": [ { "pmid": "25041740", "title": "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial", "year": 2014, "design": "Randomized, double blind, placebo controlled phase I/II trial, 4 weeks", "n": 34, "population": "Adults with hard to heal venous leg ulcers", "outcome": "LL-37 gel at 0.5 and 1.6 mg/mL twice weekly produced significantly faster ulcer healing than placebo; 3.2 mg/mL did not", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25041740/" }, { "pmid": "34687253", "title": "Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial", "year": 2021, "design": "Randomized, double blind, placebo controlled phase IIb trial", "population": "Adults with hard to heal venous leg ulcers", "outcome": "Primary endpoint not met in the full study population; a signal was reported in a subgroup with larger ulcers", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34687253/" }, { "pmid": "23246832", "title": "A comprehensive summary of LL-37, the factotum human cathelicidin peptide", "year": 2012, "design": "Narrative review", "population": "In vitro, animal, and human observational data", "outcome": "Summarizes antimicrobial, immunomodulatory, wound healing, and pro inflammatory roles, including elevated LL-37 in psoriasis and rosacea", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/23246832/" } ], "sources": [ { "id": "gronberg-2014", "type": "pubmed", "title": "Gronberg A et al. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25041740/", "pmid": "25041740", "year": 2014 }, { "id": "mahlapuu-2021", "type": "pubmed", "title": "Mahlapuu M et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial. Wound Repair Regen 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34687253/", "pmid": "34687253", "year": 2021 }, { "id": "vandamme-2012", "type": "pubmed", "title": "Vandamme D et al. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23246832/", "pmid": "23246832", "year": 2012 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "thymosin-alpha-1", "kpv", "ghk-cu", "bpc-157" ], "cluster": "immune", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "vip", "name": "VIP (vasoactive intestinal peptide)", "aliases": [ "Vasoactive intestinal polypeptide", "Aviptadil", "VIP nasal spray", "RLF-100", "Zyesami" ], "class": "Endogenous 28 amino acid neuropeptide of the secretin/glucagon family", "one_liner": "Natural nerve signaling peptide; small trials in lung artery hypertension and COVID-19 breathing failure showed no benefit; not FDA approved; FDA Category 1.", "summary": "VIP (vasoactive intestinal peptide) is a 28 amino acid neuropeptide, a signaling peptide made by nerve cells, that relaxes smooth muscle, widens blood vessels, and dampens inflammation. Its synthetic form, aviptadil, has been tested in small pulmonary hypertension (high blood pressure in the lung arteries) studies and in two randomized COVID-19 respiratory failure trials, the largest of which (TESICO, 461 patients in the aviptadil comparison) found no improvement in recovery. It is not FDA approved for any indication; it sits in FDA 503A Category 1 (nominated compounding ingredients still under evaluation), which means compounding is currently tolerated while FDA decides, and it is sold as a compounded nasal spray for chronic inflammatory conditions without trial evidence.", "mechanism": "VIP binds the G protein coupled receptors VPAC1 and VPAC2, raising intracellular cyclic AMP. This relaxes vascular, airway, and gut smooth muscle, stimulates surfactant production by type II alveolar cells, and shifts macrophages and T cells toward anti inflammatory profiles by lowering TNF alpha, IL-6, and IL-12. It is degraded within minutes in plasma, which is why inhaled, intranasal, and continuous intravenous forms are used.", "evidence_grade": "human_rct", "evidence_summary": "Small human studies exist, and the randomized ones are negative or inconclusive. Petkov 2003 reported hemodynamic improvement in 8 patients with primary pulmonary hypertension after inhaled VIP, but Leuchte 2008 found only modest acute effects and limited chronic benefit in 20 patients. In COVID-19 respiratory failure, a 196 patient 60 day RCT (Youssef 2022) did not meet its primary endpoint, and the NIH sponsored TESICO trial (Brown 2023) found no benefit of intravenous aviptadil on recovery. No randomized trial supports the intranasal VIP used for chronic inflammatory response syndrome or mold illness.", "human_evidence": "Petkov 2003: 8 patients with primary pulmonary hypertension, inhaled VIP 200 ug daily, open label, reduced pulmonary artery pressure and improved 6 minute walk over 3 months. Leuchte 2008: 20 patients with pulmonary hypertension of various causes, single inhalation produced a small acute fall in pulmonary vascular resistance; chronic treatment in 9 patients produced modest changes. Youssef 2022: 196 patients with critical COVID-19 respiratory failure randomized to intravenous aviptadil or placebo; the primary endpoint (alive and free of respiratory failure at day 60) was not significantly different. Brown 2023 (TESICO): 461 patients randomized to aviptadil versus placebo within the ACTIV-3b platform; aviptadil did not improve recovery and the trial stopped for futility.", "animal_evidence": "In rodent and sheep models VIP reduces lung injury from endotoxin and hydrochloric acid, lowers pulmonary artery pressure, and protects against sepsis. VIP knockout mice develop pulmonary hypertension and airway inflammation. VIP also reduces disease severity in mouse models of colitis, rheumatoid arthritis, and experimental autoimmune encephalomyelitis, which underlies its immunology interest.", "conditions": [ "inflammation" ], "literature_dosing": "Inhaled VIP about 200 ug per day in four divided inhalations for 3 months (Petkov 2003, primary pulmonary hypertension) or a single inhalation of 100 ug (Leuchte 2008). Intravenous aviptadil in COVID-19 trials was infused at escalating rates of 50, 100, and 150 pmol/kg/hour over 12 hours on three successive days (Youssef 2022). No dose for intranasal VIP in chronic inflammatory conditions has been established in a randomized trial.", "routes": [ "Inhaled aerosol (pulmonary hypertension studies)", "Intravenous infusion (COVID-19 trials, hospital only)", "Intranasal spray (compounded, no trial evidence)", "Intracavernosal injection combined with phentolamine (approved in some European countries for erectile dysfunction)" ], "side_effects": [ "Hypotension and flushing (vasodilation), the main dose limiting effect of intravenous use", "Diarrhea (VIP is the cause of secretory diarrhea in VIPoma)", "Tachycardia", "Nasal irritation with intranasal use (anecdotal)", "Hyperglycemia reported in infusion studies" ], "interactions": [ "Additive blood pressure lowering with antihypertensives, PDE5 inhibitors, and nitrates (theoretical, based on mechanism)", "No formal drug interaction studies published" ], "contraindications": [ "Hypotension or hemodynamic instability outside a monitored setting", "Pregnancy and breastfeeding (no data)", "Uncontrolled diarrhea" ], "wada_status": "unclear", "fda_status": "under_review", "compounding_status": "Not an FDA approved drug in the United States. An aviptadil and phentolamine combination is approved in some European countries for erectile dysfunction, and aviptadil was studied under FDA authorized COVID-19 trials but never authorized or approved. Vasoactive intestinal peptide appears on the FDA 503A bulk drug substances list as Category 1 (nominated and under evaluation), so 503A pharmacies may compound it while FDA finishes its review; it has not been placed on the bulks list and was not part of the April 2026 Category 2 removals or the July 2026 advisory committee recommendations.", "typical_cost": "Roughly 150 to 400 USD per month for compounded intranasal VIP through a prescribing clinic, plus consultation fees. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Prescription from a licensed provider filled by a 503A compounding pharmacy as an intranasal spray, while VIP remains in FDA Category 1.", "Not available as an FDA approved product.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is VIP peptide legal and FDA approved?", "a": "It is not FDA approved. It is listed in FDA 503A Category 1, meaning it was nominated for the compounding bulks list (ingredients pharmacies may use to compound drugs for individual patients) and is still under evaluation, so licensed 503A pharmacies can compound it with a prescription while FDA decides. It was not among the peptides FDA moved off Category 2 in April 2026 and was not part of the July 2026 advisory committee votes.", "source_ids": [ "fda-503a-bulks", "fda-503a-category-pdf" ] }, { "q": "Does VIP nasal spray work for CIRS or mold illness?", "a": "There is no randomized trial of intranasal VIP for chronic inflammatory response syndrome, mold illness, or any related diagnosis. The claim rests on VIP's anti inflammatory effects in animals and on uncontrolled case series. The only randomized human VIP trials are in pulmonary hypertension and COVID-19, and the COVID-19 trials were negative.", "source_ids": [ "youssef-2022", "brown-2023" ] }, { "q": "Did VIP (aviptadil) work for COVID-19?", "a": "No. A 196 patient randomized trial did not meet its primary endpoint of being alive and free of respiratory failure at 60 days, and the NIH sponsored TESICO trial of 461 patients found no improvement in recovery with intravenous aviptadil and was stopped for futility. FDA did not authorize it.", "source_ids": [ "youssef-2022", "brown-2023" ] }, { "q": "What are the side effects of VIP?", "a": "VIP is a vasodilator, so low blood pressure, flushing, and fast heart rate are the main effects and limited the intravenous dose in COVID-19 trials. It stimulates intestinal secretion, so diarrhea can occur. Intranasal use has no controlled safety data; nasal irritation is reported anecdotally.", "source_ids": [ "youssef-2022", "leuchte-2008" ] }, { "q": "How is VIP taken?", "a": "In pulmonary hypertension studies it was inhaled as an aerosol (about 200 ug per day in four divided doses). In COVID-19 trials it was a 12 hour intravenous infusion on three consecutive days in the ICU. Compounded products are nasal sprays. No dose for the nasal spray has been set by a randomized trial.", "source_ids": [ "petkov-2003", "youssef-2022" ] }, { "q": "How much does VIP nasal spray cost?", "a": "Compounded intranasal VIP typically runs 150 to 400 USD per month through a prescribing clinic, before consultation fees. Research chemical vials are cheaper but not lawful for human use. Prices were checked on the last verified date and vary by pharmacy.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is VIP banned by WADA?", "a": "Unclear. VIP is not named on the WADA Prohibited List. Because an aviptadil product is approved in some countries, it does not clearly fall under S0 (non-approved substances), but it is not covered by any explicit exemption either. Athletes should ask their anti-doping organization before use.", "source_ids": [ "wada-list" ] }, { "q": "VIP vs thymosin alpha-1 for immune modulation?", "a": "Neither has randomized evidence for the immune support uses they are marketed for. Thymosin alpha-1 has approved indications abroad and hepatitis B trials; VIP's randomized trials are in pulmonary hypertension and COVID-19 and did not show benefit in the COVID-19 setting. Both are compounded in the US under different regulatory footing, and neither is FDA approved.", "source_ids": [ "brown-2023", "fda-503a-bulks" ] } ], "studies": [ { "pmid": "12727925", "title": "Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension", "year": 2003, "design": "Open label pilot study, 3 months", "n": 8, "population": "Adults with primary pulmonary hypertension", "outcome": "Inhaled VIP reduced mean pulmonary artery pressure and pulmonary vascular resistance and improved 6 minute walk distance; no control group", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/12727925/" }, { "pmid": "18978135", "title": "Inhalation of vasoactive intestinal peptide in pulmonary hypertension", "year": 2008, "design": "Acute hemodynamic study with a chronic open label extension", "n": 20, "population": "Adults with pulmonary hypertension of various etiologies", "outcome": "Single inhalation produced a small acute fall in pulmonary vascular resistance; 3 months of inhaled VIP in 9 patients produced modest hemodynamic changes", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/18978135/" }, { "pmid": "36044317", "title": "The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial", "year": 2022, "design": "Randomized, double blind, placebo controlled trial, 60 days", "n": 196, "population": "Adults with critical COVID-19 and respiratory failure", "outcome": "Primary endpoint (alive and free of respiratory failure at day 60) not significantly different from placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/36044317/" }, { "pmid": "37348524", "title": "Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial", "year": 2023, "design": "Randomized, double blind, placebo controlled platform trial (ACTIV-3b)", "n": 461, "population": "Adults hospitalized with COVID-19 acute hypoxemic respiratory failure", "outcome": "Aviptadil did not improve recovery versus placebo; enrollment stopped for futility", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37348524/" } ], "sources": [ { "id": "petkov-2003", "type": "pubmed", "title": "Petkov V et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12727925/", "pmid": "12727925", "year": 2003 }, { "id": "leuchte-2008", "type": "pubmed", "title": "Leuchte HH et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18978135/", "pmid": "18978135", "year": 2008 }, { "id": "youssef-2022", "type": "pubmed", "title": "Youssef JG et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial. Crit Care Med 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36044317/", "pmid": "36044317", "year": 2022 }, { "id": "brown-2023", "type": "pubmed", "title": "Brown SM et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO). Lancet Respir Med 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37348524/", "pmid": "37348524", "year": 2023 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-503a-category-pdf", "type": "fda", "title": "FDA: 503A bulk drug substances category lists (PDF, updated 2026; vasoactive intestinal peptide listed in Category 1)", "url": "https://www.fda.gov/media/94155/download", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "thymosin-alpha-1", "kpv", "ll-37", "secretin" ], "cluster": "immune", "last_verified": "2026-09-27", "review_status": "draft", "version": 2 }, { "slug": "pnc-27", "name": "PNC-27", "aliases": [ "PNC 27", "p53 HDM-2 binding peptide", "PNC-27 anticancer peptide" ], "class": "Synthetic 32 amino acid peptide: residues 12 to 26 of the p53 HDM-2 binding domain fused to the penetratin membrane transit sequence", "one_liner": "A lab-stage anticancer peptide tested only in lab-dish cells and mice; no human trials; FDA has warned patients not to use PNC-27 products sold online.", "summary": "PNC-27 is a designed peptide that links a fragment of the p53 protein (a natural tumor suppressor) to a sequence that carries it into cells; in lab dishes it forms pores in the membranes of cancer cells that display the protein HDM-2 and kills them while sparing normal cells. All evidence is from cell lines and a small number of mouse xenograft experiments (human tumors grown in mice), and no human trial has ever been registered or published. It is not FDA approved and never has been reviewed; in January 2017 FDA warned cancer patients not to use PNC-27 products sold online after finding bacterial contamination in a sample.", "mechanism": "The p53 derived segment of PNC-27 binds HDM-2 (MDM2), which is expressed on the plasma membrane of many cancer cells but not on normal cells. On binding, the peptide oligomerizes and forms transmembrane pores, causing rapid necrotic cell death within hours (the authors call this poptosis). Later work suggests PNC-27 also disrupts mitochondrial membranes in cancer cells. Cells lacking membrane HDM-2 are not affected in these assays.", "evidence_grade": "animal_only", "evidence_summary": "In vitro work from one research group shows PNC-27 kills a range of cancer cell lines (pancreatic, breast, leukemia, cervical, and others) by membrane pore formation, with no effect on untransformed cells at the same concentrations. Mouse xenograft experiments with the related PNC-28 peptide showed tumor shrinkage. No human trial, dose finding study, or pharmacokinetic study has been published, so the evidence is graded animal-only and human efficacy and safety are unknown.", "human_evidence": "No indexed human trial identified. No clinical trial of PNC-27 appears in the published literature, and FDA has stated it has not evaluated or approved PNC-27 for any disease. Products sold online as nebulized solutions, intravenous solutions, or suppositories have never been tested in people.", "animal_evidence": "Mouse xenograft studies with the sister peptide PNC-28 reported necrosis and shrinkage of human pancreatic cancer implants. PNC-27 itself has been characterized mostly in cell culture: it kills HDM-2 positive cancer cell lines within hours by pore formation and has no cytotoxicity toward normal fibroblasts, keratinocytes, or hematopoietic cells in the same assays. Toxicology, pharmacokinetics, and immunogenicity in animals have not been reported.", "conditions": [], "literature_dosing": "Not established in human literature. Cell culture studies used micromolar concentrations in vitro; no animal or human dose can be derived from them.", "routes": [ "In vitro exposure only (published studies)", "Nebulized solution, intravenous solution, vaginal or rectal suppository (as sold online, untested)" ], "side_effects": [ "No human safety data of any kind", "Contamination risk: FDA found the bacterium Variovorax paradoxus in a PNC-27 inhalation solution sold online", "Theoretical risk of pore formation in any cell expressing membrane HDM-2, immune reactions to a foreign peptide, and infusion reactions", "Delay of proven cancer treatment while using it" ], "interactions": [ "No interaction studies exist", "Unknown effect on concurrent chemotherapy, immunotherapy, or radiation" ], "contraindications": [ "Any use outside a registered clinical trial (none exists)", "Pregnancy and breastfeeding (no data)", "Immunocompromised patients face the highest risk from contaminated products" ], "wada_status": "prohibited", "fda_status": "unscheduled", "compounding_status": "Not an FDA approved drug and never submitted for FDA review. PNC-27 has not been nominated for the 503A bulks list and does not appear in any FDA compounding category, so licensed pharmacies cannot lawfully compound it. FDA issued a public warning in January 2017 telling cancer patients not to buy or use PNC-27 products after laboratory testing found bacterial contamination in a solution marketed for inhalation.", "typical_cost": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "access_path": [ "Not legally available for human use in the United States.", "No registered clinical trial is recruiting as of the last verified date.", "Products sold online are unapproved and FDA has specifically warned against them." ], "faqs": [ { "q": "Is PNC-27 legal or FDA approved?", "a": "No. PNC-27 has never been reviewed or approved by FDA and is not on any compounding list (FDA's lists of ingredients pharmacies may use), so no licensed pharmacy can make it. In January 2017 FDA warned cancer patients not to purchase or use PNC-27 products sold online after an FDA laboratory found the bacterium Variovorax paradoxus in a sample marketed for inhalation.", "source_ids": [ "fda-pnc27-warning" ] }, { "q": "Does PNC-27 cure cancer?", "a": "There is no evidence in people. PNC-27 kills cancer cell lines in a dish by punching holes in cells that display HDM-2 on their surface, and a related peptide shrank pancreatic tumors in mice. No human trial has ever been published. Cell culture results routinely fail to translate to patients, and using an untested product instead of proven treatment can be harmful.", "source_ids": [ "krzesaj-2024", "bowne-2008", "fda-pnc27-warning" ] }, { "q": "How does PNC-27 work?", "a": "It fuses a piece of the p53 protein, which binds HDM-2, to a cell penetrating sequence. Many cancer cells carry HDM-2 in their outer membrane; PNC-27 binds it, clusters, and forms pores that cause the cell to die by necrosis within hours. Normal cells without membrane HDM-2 are unaffected in the assays. This mechanism has been shown only in cell culture.", "source_ids": [ "krzesaj-2024", "pincus-2024" ] }, { "q": "What are the side effects of PNC-27?", "a": "Unknown, because it has never been given to people in a study. The documented harm so far is contamination: FDA found live bacteria in a PNC-27 solution sold online, which could cause serious infection in people with cancer or weakened immunity. Theoretical risks include damage to any normal tissue expressing membrane HDM-2 and immune reactions.", "source_ids": [ "fda-pnc27-warning", "pincus-2024" ] }, { "q": "How is PNC-27 taken?", "a": "It is not. Published work is confined to cell culture and mice. Online sellers offer nebulizer solutions, intravenous solutions, and suppositories, none of which have been studied for absorption, dose, or safety in humans.", "source_ids": [ "fda-pnc27-warning" ] }, { "q": "How much does PNC-27 cost?", "a": "It is not available through any licensed channel, so there is no legitimate price. Unregulated sellers have charged thousands of dollars per course for unapproved, untested product. Any money spent is at risk with no evidence of benefit.", "source_ids": [ "fda-pnc27-warning" ] }, { "q": "Is PNC-27 banned by WADA?", "a": "Yes, by default. PNC-27 has no approval from any government health authority for human use, so it falls under section S0 of the WADA Prohibited List and is prohibited at all times. It has no performance rationale in any case.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "38802154", "title": "Anti-cancer peptide PNC-27 kills cancer cells by unique interactions with plasma membrane-bound hdm-2 and with mitochondrial membranes causing mitochondrial disruption", "year": 2024, "design": "In vitro cell culture study", "population": "Human cancer cell lines and untransformed control cells", "outcome": "PNC-27 induced pore formation and mitochondrial disruption in cancer cells expressing membrane HDM-2 with no effect on normal cells", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/38802154/" }, { "pmid": "38927351", "title": "Poptosis or peptide-induced transmembrane pore formation: a novel way to kill cancer cells without affecting normal cells", "year": 2024, "design": "Narrative review by the originating laboratory", "population": "Cell line and mouse xenograft data on PNC-27 and PNC-28", "outcome": "Summarizes the membrane HDM-2 targeting mechanism and preclinical selectivity; no human data", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/38927351/" }, { "pmid": "18931881", "title": "The penetratin sequence in the anticancer PNC-28 peptide causes tumor cell necrosis rather than apoptosis of human pancreatic cancer cells", "year": 2008, "design": "In vitro and mouse xenograft study", "population": "Human pancreatic cancer cell lines and nude mice bearing xenografts", "outcome": "The related peptide PNC-28 caused tumor cell necrosis in culture and tumor shrinkage in mice", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/18931881/" } ], "sources": [ { "id": "krzesaj-2024", "type": "pubmed", "title": "Krzesaj P et al. Anti-cancer peptide PNC-27 kills cancer cells by unique interactions with plasma membrane-bound hdm-2 and with mitochondrial membranes. Ann Clin Lab Sci 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38802154/", "pmid": "38802154", "year": 2024 }, { "id": "pincus-2024", "type": "pubmed", "title": "Pincus MR et al. Poptosis or peptide-induced transmembrane pore formation: a novel way to kill cancer cells without affecting normal cells. Biomedicines 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38927351/", "pmid": "38927351", "year": 2024 }, { "id": "bowne-2008", "type": "pubmed", "title": "Bowne WB et al. The penetratin sequence in the anticancer PNC-28 peptide causes tumor cell necrosis rather than apoptosis of human pancreatic cancer cells. Ann Surg Oncol 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18931881/", "pmid": "18931881", "year": 2008 }, { "id": "fda-pnc27-warning", "type": "fda", "title": "FDA warns cancer patients not to use PNC-27 products for treatment (January 2017) (Wayback Machine capture of the FDA page, March 7, 2026)", "url": "https://web.archive.org/web/20260307095200/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-cancer-patients-not-use-pnc-27-products-treatment", "year": 2017 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "thymosin-alpha-1", "ll-37", "foxo4-dri" ], "cluster": "immune", "last_verified": "2026-09-22", "review_status": "draft", "version": 2 }, { "slug": "dsip", "name": "DSIP (delta sleep-inducing peptide)", "aliases": [ "Delta sleep-inducing peptide", "Emideltide", "DSIP peptide", "Deltaran" ], "class": "Endogenous nonapeptide (9 amino acids) first isolated from the cerebral venous blood of rabbits during induced sleep", "one_liner": "A 9 amino acid peptide with small, mixed 1980s insomnia trials; off FDA's Category 2 risk list since April 2026 but rejected by FDA advisers in July 2026.", "summary": "DSIP (delta sleep-inducing peptide) is a nine amino acid peptide isolated in 1977 from blood draining the brains of rabbits in induced sleep and later found in humans. Three small double blind trials (neither patients nor researchers knew who got the peptide) in chronic insomnia in the late 1980s and early 1990s gave inconsistent results, with modest changes in sleep on some measures and none on others, and a 2006 review concluded its role in the body is still unresolved. It is not FDA approved; FDA removed it from the 503A Category 2 list (compounding ingredients flagged for significant safety risks) on April 15, 2026, but the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) voted against adding it to the 503A bulks list (ingredients pharmacies may use to compound drugs for individual patients) on July 23 to 24, 2026.", "mechanism": "Uncertain. DSIP does not bind a known dedicated receptor. Proposed actions include modulation of GABAergic and glutamatergic transmission, effects on the hypothalamic pituitary axis (it lowers stress induced ACTH and cortisol release in some animal studies), and influence on the circadian regulation of slow wave sleep. Its very short plasma half life and poor blood brain barrier penetration raise doubts about how injected DSIP acts on the brain at all.", "evidence_grade": "human_rct", "evidence_summary": "Evidence is limited to small double blind placebo controlled trials from 1987 to 1992 in chronic insomnia, none larger than a few dozen patients. Schneider-Helmert 1987 reported improved 24 hour sleep wake behavior in severe chronic insomnia; Monti 1987 found only short lived effects; Bes 1992 found effects that did not persist and were inconsistent across measures. No modern trial exists, and a 2006 review called DSIP an unresolved riddle. Human evidence is therefore graded as randomized but weak, old, and unreplicated.", "human_evidence": "Schneider-Helmert 1987: severe chronic insomnia patients given intravenous DSIP in a double blind crossover design showed improvements in sleep efficiency and daytime alertness. Monti 1987: chronic insomniacs given DSIP for several nights showed some improvement in sleep latency early in treatment that was not sustained. Bes 1992: double blind study in chronic insomnia found small effects on some polysomnographic measures with no consistent overall benefit. No dose response, long term, or oral study exists, and no trial has tested the subcutaneous form sold today.", "animal_evidence": "In rabbits and rats, DSIP infused into the brain or bloodstream increased delta (slow wave) EEG activity in some experiments and not in others; the original sleep inducing effect was difficult to replicate across laboratories. Rodent studies also report reduced stress hormone release, antioxidant effects, and anticonvulsant activity. The animal literature is decades old and contradictory.", "conditions": [ "sleep" ], "literature_dosing": "Human trials used intravenous DSIP at approximately 25 nmol/kg (about 0.02 mg/kg) given in the evening for a small number of nights (Schneider-Helmert 1987; Monti 1987). No subcutaneous, intranasal, or oral human dose has been studied.", "routes": [ "Intravenous infusion (clinical trials)", "Subcutaneous injection (as sold, no human data)", "Intranasal (as sold, no human data)" ], "side_effects": [ "No adverse effects beyond placebo were reported in the small trials, but total human exposure is a few dozen patients", "Headache and drowsiness reported anecdotally", "Injection site reactions reported anecdotally", "No long term safety data" ], "interactions": [ "No formal interaction studies exist", "Additive sedation with hypnotics, alcohol, opioids, or benzodiazepines is plausible but untested" ], "contraindications": [ "Pregnancy and breastfeeding (no data)", "Competitive athletes subject to WADA testing (prohibited under S0)", "Uncontrolled depression or sleep apnea, where an untested sedative peptide can mask treatable causes of poor sleep" ], "wada_status": "prohibited", "fda_status": "not_eligible", "compounding_status": "Not an FDA approved drug. DSIP was placed on the FDA 503A Category 2 list in 2023 and was one of the peptides FDA now lists as withdrawn from 503A Category 2 (page current as of April 22, 2026) after the nominations were withdrawn. At the July 23 to 24, 2026 Pharmacy Compounding Advisory Committee meeting the committee voted against adding DSIP to the 503A bulks list, citing inadequate evidence of safety and effectiveness. Pending FDA's final action, compounding pharmacies have no basis to compound it. Not eligible for 503B outsourcing.", "typical_cost": "Products sold as research chemicals are not lawful for human use and are not verified for identity or purity. Not available through licensed compounding or telehealth channels.", "access_path": [ "Not available as an FDA approved product.", "Not compounded following the July 2026 advisory committee vote against listing.", "Products labeled research use only are not lawful for human use and are not verified for purity." ], "faqs": [ { "q": "Is DSIP legal in the United States?", "a": "It is not FDA approved, and it cannot currently be compounded (custom-made by a pharmacy). FDA removed DSIP from its 503A Category 2 list (compounding ingredients flagged for significant safety risks) on April 15, 2026, but at the July 2026 meeting the Pharmacy Compounding Advisory Committee (FDA's outside expert panel) voted against adding it to the bulks list of ingredients pharmacies may use, so pharmacies have no lawful pathway to make it. Products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does DSIP work for insomnia or sleep?", "a": "The evidence is thin and old. Three small double blind trials from 1987 to 1992 in chronic insomnia found modest short term effects on some sleep measures and none on others, and no trial has been done since. A 2006 review concluded DSIP's role in sleep is unresolved. It has never been tested in the subcutaneous form sold online.", "source_ids": [ "schneider-helmert-1987", "monti-1987", "bes-1992", "kovalzon-2006" ] }, { "q": "What are the side effects of DSIP?", "a": "The small intravenous trials did not report side effects beyond placebo, but fewer than 100 people have received it in published studies and none for more than a few nights. Anecdotal reports mention headache, grogginess, and injection site irritation. There is no long term safety data.", "source_ids": [ "monti-1987", "bes-1992" ] }, { "q": "How is DSIP taken?", "a": "In the trials it was given intravenously in the evening at about 25 nmol/kg for a few nights. Products sold online are subcutaneous injection vials or nasal sprays, and no human study has used those routes or established a dose for them.", "source_ids": [ "schneider-helmert-1987", "monti-1987" ] }, { "q": "How much does DSIP cost?", "a": "No licensed pharmacy channel exists. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is DSIP banned by WADA?", "a": "Yes. DSIP has no approval from any government health authority for human use, so it is prohibited at all times under section S0 of the WADA Prohibited List.", "source_ids": [ "wada-list" ] }, { "q": "Why did the FDA advisory committee reject DSIP?", "a": "At the July 23 to 24, 2026 Pharmacy Compounding Advisory Committee meeting, DSIP was one of the nominated peptides the committee voted not to recommend for the 503A bulks list, while BPC-157, KPV, TB-500, MOTS-c, semax, and epitalon were recommended. The committee's standard is documented safety, effectiveness, and a history of use, and DSIP's human data consist of a few small trials from the 1980s.", "source_ids": [ "fda-pcac-2026", "kovalzon-2006" ] }, { "q": "DSIP vs epitalon for sleep: which has more evidence?", "a": "Neither has a modern randomized trial for sleep. DSIP has three small placebo controlled insomnia trials from decades ago with inconsistent results; epitalon's human data are mostly Russian observational reports. Epitalon was recommended by the advisory committee in July 2026 and DSIP was not, which changes their compounding outlook but not the strength of their sleep evidence.", "source_ids": [ "bes-1992", "fda-pcac-2026" ] } ], "studies": [ { "pmid": "3622582", "title": "Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia", "year": 1987, "design": "Double blind placebo controlled crossover study", "population": "Adults with severe chronic insomnia", "outcome": "Intravenous DSIP improved sleep efficiency and daytime performance measures relative to placebo in a small sample", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/3622582/" }, { "pmid": "3583493", "title": "Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs", "year": 1987, "design": "Double blind placebo controlled short term study", "population": "Adults with chronic insomnia", "outcome": "Early improvement in sleep latency that was not sustained across the treatment period", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/3583493/" }, { "pmid": "1299794", "title": "Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study", "year": 1992, "design": "Double blind placebo controlled polysomnographic study", "population": "Adults with chronic insomnia", "outcome": "Small changes on some polysomnographic measures with no consistent overall improvement in sleep", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/1299794/" }, { "pmid": "16539679", "title": "Delta sleep-inducing peptide (DSIP): a still unresolved riddle", "year": 2006, "design": "Narrative review", "population": "Animal and human literature 1977 to 2005", "outcome": "Concludes that DSIP's sleep promoting role is unproven and its receptor and physiological function remain unknown", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/16539679/" } ], "sources": [ { "id": "schneider-helmert-1987", "type": "pubmed", "title": "Schneider-Helmert D. Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia. Eur Neurol 1987", "url": "https://pubmed.ncbi.nlm.nih.gov/3622582/", "pmid": "3622582", "year": 1987 }, { "id": "monti-1987", "type": "pubmed", "title": "Monti JM et al. Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs. Int J Clin Pharmacol Res 1987", "url": "https://pubmed.ncbi.nlm.nih.gov/3583493/", "pmid": "3583493", "year": 1987 }, { "id": "bes-1992", "type": "pubmed", "title": "Bes F et al. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. Neuropsychobiology 1992", "url": "https://pubmed.ncbi.nlm.nih.gov/1299794/", "pmid": "1299794", "year": 1992 }, { "id": "kovalzon-2006", "type": "pubmed", "title": "Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16539679/", "pmid": "16539679", "year": 2006 }, { "id": "fda-503a-bulks", "type": "fda", "title": "FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act", "year": 2026 }, { "id": "fda-pcac-2026", "type": "fda", "title": "FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)", "url": "https://www.fda.gov/advisory-committees/human-drug-advisory-committees/pharmacy-compounding-advisory-committee", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "epitalon", "selank", "pinealon" ], "cluster": "other", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "DSIP peptide: sleep evidence and legal status", "h1": "DSIP (delta sleep-inducing peptide)" } }, { "slug": "teriparatide", "name": "Teriparatide", "aliases": [ "Forteo", "PTH (1-34)", "Recombinant human parathyroid hormone 1-34", "Bonsity", "rhPTH(1-34)" ], "class": "Recombinant fragment of human parathyroid hormone (amino acids 1 to 34), a bone anabolic agent", "one_liner": "FDA approved daily osteoporosis injection that cut new spine fractures by 65% in its pivotal trial and beat risedronate head to head.", "summary": "Teriparatide is the active 34 amino acid fragment of parathyroid hormone that, injected daily, builds new bone; it has been FDA approved since 2002 to treat osteoporosis (thin, fragile bones) in people at high risk of fracture. In the pivotal trial of 1,637 postmenopausal women, 20 micrograms daily reduced new vertebral (spine) fractures by 65% and nonvertebral fragility fractures (breaks elsewhere from minor falls) by 53% over a median 21 months, and in the VERO trial it caused fewer new vertebral fractures than risedronate, a standard osteoporosis pill (5.4% versus 12.0%). It is a prescription drug available as brand, biosimilar (a near copy of a biologic drug), and generic products, with no compounding role.", "mechanism": "Given once daily as a brief pulse, teriparatide activates the PTH1 receptor on osteoblasts and stimulates new bone formation more than resorption, increasing trabecular bone density and connectivity. Continuous exposure to parathyroid hormone has the opposite, catabolic effect, which is why the drug is dosed as a single daily subcutaneous injection. The anabolic window narrows after 18 to 24 months as resorption catches up.", "evidence_grade": "human_rct", "evidence_summary": "Large randomized placebo controlled and active comparator trials. Neer 2001 (n = 1,637) found 20 ug daily reduced new vertebral fractures from 14% to 5% (relative risk 0.35) and nonvertebral fragility fractures from 6% to 3% (relative risk 0.47) and raised lumbar spine bone density by 9% over a median 21 months. VERO 2018 (n = 1,360) found new vertebral fractures in 5.4% on teriparatide versus 12.0% on risedronate over 24 months (risk ratio 0.44).", "human_evidence": "Neer 2001: 1,637 postmenopausal women with prior vertebral fractures randomized to placebo, 20 ug, or 40 ug teriparatide daily; the trial was stopped early after a median 21 months. New vertebral fractures occurred in 14% on placebo versus 5% on 20 ug (relative risk 0.35, 95% CI 0.22 to 0.55); nonvertebral fragility fractures 6% versus 3%. VERO 2018: 1,360 postmenopausal women with severe osteoporosis randomized to teriparatide 20 ug daily or oral risedronate 35 mg weekly for 24 months; new vertebral fractures 5.4% versus 12.0% (risk ratio 0.44, 95% CI 0.29 to 0.68), clinical fractures 4.8% versus 9.8%.", "animal_evidence": "In rats given teriparatide for most of their lifespan at 3 to 60 times the human exposure, osteosarcoma occurred in a dose dependent manner. This finding led to the original boxed warning and the 2 year lifetime limit; postmarketing surveillance over nearly two decades found no increased osteosarcoma in humans, and FDA removed the boxed warning in 2020. Monkey studies showed bone gain without tumors.", "conditions": [], "literature_dosing": "FDA label (Forteo, DailyMed): 20 mcg injected subcutaneously once daily into the thigh or abdominal region, with supplemental calcium and vitamin D based on individual need. The first doses are given where the patient can sit or lie down in case of orthostatic hypotension. Use for more than 2 years during a patient's lifetime should be considered only if the patient remains at or has returned to a high risk for fracture. In Neer 2001 the 40 mcg dose added no fracture benefit over 20 mcg and caused more side effects.", "routes": [ "Subcutaneous injection once daily (prefilled pen)" ], "side_effects": [ "Transient hypercalcemia (11% of the 20 ug group in Neer 2001 versus 2% placebo, usually mild)", "Dizziness (9% versus 6%) and leg cramps (3% versus 1%)", "Nausea, headache, and orthostatic hypotension in the first doses", "Injection site reactions", "Hyperuricemia and increased urinary calcium", "Osteosarcoma in rats at high lifetime doses; no increase detected in humans in postmarketing surveillance, boxed warning removed in 2020" ], "interactions": [ "Digoxin: teriparatide induced hypercalcemia can increase sensitivity to digoxin toxicity", "Hydrochlorothiazide: modest additive rise in serum calcium", "Bisphosphonates or denosumab given at the same time blunt the bone density gain; sequential use is standard" ], "contraindications": [ "Hypersensitivity to teriparatide", "Conditions with increased baseline osteosarcoma risk: Paget disease of bone, unexplained elevated alkaline phosphatase, open epiphyses, prior skeletal radiation (per the 2020 label these are risk factors to avoid rather than absolute bars)", "Bone metastases or skeletal malignancy", "Pre-existing hypercalcemia or hyperparathyroidism", "Pregnancy and breastfeeding" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Forteo in November 2002 for postmenopausal women with osteoporosis at high fracture risk, men with primary or hypogonadal osteoporosis, and glucocorticoid induced osteoporosis. A 505(b)(2) product (Bonsity, 2019) and generic teriparatide injections have since been approved. In November 2020 FDA approved label changes removing the boxed warning for osteosarcoma and the 2 year lifetime treatment limit. Because approved products exist, compounding teriparatide is not permitted except in narrow patient specific circumstances.", "typical_cost": "Brand Forteo has a manufacturer list price of 4,289.89 USD per pen, and one pen is a 28 day supply. Generic teriparatide pens cost about 1,036 to 1,146 USD with a discount card at the lowest-priced pharmacies, against average retail prices of about 2,977 to 3,214 USD (checked 2026-09-22). The Forteo savings card can bring a covered commercial prescription to 4 USD a month. Medicare Part D and most commercial plans cover it with prior authorization for high fracture risk.", "access_path": [ "Prescription from a licensed provider (usually endocrinology, rheumatology, or primary care) filled at a retail or specialty pharmacy.", "Prior authorization typically requires a documented fragility fracture, very low bone density, or failure of oral bisphosphonates.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is teriparatide (Forteo) FDA approved, and what is it used for?", "a": "Yes, since 2002. The Forteo label covers postmenopausal women with osteoporosis at high risk for fracture (where it reduces vertebral and nonvertebral fractures), men with primary or hypogonadal (low testosterone) osteoporosis at high risk for fracture (to increase bone mass), and men and women with osteoporosis from sustained systemic glucocorticoid therapy, long term steroid medicines such as prednisone, at high fracture risk, including those who failed or cannot tolerate other therapy. Generic and 505(b)(2) versions, copies approved through a shortened FDA pathway, followed. It is prescription only.", "source_ids": [ "fda-forteo-label" ] }, { "q": "How well does teriparatide prevent fractures?", "a": "In the pivotal trial of 1,637 postmenopausal women with prior vertebral fractures, 20 ug daily for a median 21 months reduced new vertebral fractures from 14% to 5% (a 65% relative reduction) and nonvertebral fragility fractures from 6% to 3%. In the VERO head to head trial, 5.4% of women on teriparatide had a new vertebral fracture over 2 years versus 12.0% on risedronate.", "source_ids": [ "neer-2001", "vero-2018" ] }, { "q": "Does teriparatide cause cancer?", "a": "Rats given teriparatide for most of their lives at 3 to 60 times human exposure developed osteosarcoma, which led to a boxed warning and a 2 year lifetime limit at approval. After nearly two decades of postmarketing surveillance found no increase in osteosarcoma in treated patients, FDA removed the boxed warning and the 2 year limit in November 2020. People with Paget disease, prior skeletal radiation, or open growth plates are still advised to avoid it.", "source_ids": [ "fda-forteo-label", "neer-2001" ] }, { "q": "What are the side effects of teriparatide?", "a": "The most common are transient rises in blood calcium (11% versus 2% on placebo in the pivotal trial), dizziness (9% versus 6%), leg cramps, nausea, and injection site reactions. Orthostatic lightheadedness can occur after the first few doses, so the label advises sitting or lying down for the first injections.", "source_ids": [ "neer-2001", "fda-forteo-label" ] }, { "q": "What is the teriparatide (Forteo) dose on the FDA label?", "a": "20 mcg injected under the skin of the thigh or abdomen once a day from a prefilled pen, with calcium and vitamin D as needed. The label advises giving the first doses sitting or lying down because of orthostatic hypotension, and says use beyond 2 years in a lifetime should be considered only if fracture risk remains high. Bone gains fade after stopping unless an antiresorptive such as a bisphosphonate or denosumab follows.", "source_ids": [ "fda-forteo-label", "vero-2018" ] }, { "q": "How much does teriparatide cost?", "a": "Brand Forteo has a manufacturer list price of 4,289.89 USD per pen, a 28 day supply. A published discount-card price source checked 2026-09-22 showed generic teriparatide pens from about 1,036 to 1,146 USD with a discount card, against average retail prices of about 2,977 to 3,214 USD. Most insurers including Medicare Part D cover it with prior authorization for high fracture risk, and the Forteo savings card lets eligible commercially insured patients pay as little as 4 USD a month.", "source_ids": [ "price-list-disclosure", "price-cash-generic", "price-cash-generic-alt", "price-savings", "fda-forteo-label" ] }, { "q": "Is teriparatide banned by WADA?", "a": "No. Parathyroid hormone analogs are not named on the WADA Prohibited List. Athletes should still confirm with their anti-doping organization, since the list is updated every January.", "source_ids": [ "wada-list" ] }, { "q": "Teriparatide vs abaloparatide: what is the difference?", "a": "Both are daily injectable PTH receptor agonists. Teriparatide is PTH(1-34); abaloparatide is a PTH related protein analog that favors a transient receptor conformation and causes less hypercalcemia. Abaloparatide's placebo controlled trial showed an 86% relative reduction in new vertebral fractures, teriparatide's showed 65%, but the trials enrolled different populations and no fracture endpoint trial has compared them directly. Teriparatide has generics and a longer safety record.", "source_ids": [ "neer-2001", "fda-forteo-label" ] } ], "studies": [ { "pmid": "11346808", "title": "Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis", "year": 2001, "design": "Randomized, double blind, placebo controlled trial, median 21 months", "n": 1637, "population": "Postmenopausal women with at least one prior vertebral fracture", "outcome": "New vertebral fractures 5% with 20 ug versus 14% placebo (relative risk 0.35); nonvertebral fragility fractures 3% versus 6%; lumbar spine BMD up 9%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/11346808/" }, { "pmid": "29129436", "title": "Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial", "year": 2018, "design": "Randomized, double blind, double dummy, active comparator trial, 24 months", "n": 1360, "population": "Postmenopausal women with severe osteoporosis and at least two moderate or one severe vertebral fracture", "outcome": "New vertebral fractures 5.4% with teriparatide versus 12.0% with risedronate (risk ratio 0.44); clinical fractures 4.8% versus 9.8%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/29129436/" } ], "sources": [ { "id": "neer-2001", "type": "pubmed", "title": "Neer RM et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11346808/", "pmid": "11346808", "year": 2001 }, { "id": "vero-2018", "type": "pubmed", "title": "Kendler DL et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO). Lancet 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29129436/", "pmid": "29129436", "year": 2018 }, { "id": "fda-forteo-label", "type": "fda", "title": "FDA prescribing information for Forteo (teriparatide injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "price-list-disclosure", "type": "other", "title": "Manufacturer state price disclosure sheet for teriparatide injection (brand): wholesale acquisition cost per pen, accessed 2026-09-22", "url": "https://pricinginfo.lilly.com/assets/pdf/Connecticut_Disclosure_Sheet-Forteo.pdf", "year": 2025 }, { "id": "price-cash-generic", "type": "other", "title": "Published cash-price comparison for generic teriparatide injection pens, discount-card and average retail prices, accessed 2026-09-22", "url": "https://www.goodrx.com/teriparatide-injection", "year": 2026 }, { "id": "price-cash-generic-alt", "type": "other", "title": "Published cash-price comparison for generic teriparatide referencing the brand pen, discount-card and average retail prices, accessed 2026-09-22", "url": "https://www.goodrx.com/forteo", "year": 2026 }, { "id": "price-savings", "type": "other", "title": "Manufacturer savings and support program terms for brand teriparatide injection, accessed 2026-09-22", "url": "https://forteo.lilly.com/savings-and-support", "year": 2026 } ], "related": [ "abaloparatide", "calcitonin", "tesamorelin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Teriparatide (Forteo): uses, side effects, and dosing", "description": "Forteo is teriparatide, a daily bone-building injection for osteoporosis at high fracture risk. FDA label uses, the 20 mcg dose, side effects, and cost.", "h1": "Teriparatide (Forteo)" } }, { "slug": "abaloparatide", "name": "Abaloparatide", "aliases": [ "Tymlos", "BA058", "PTHrP (1-34) analog", "Abaloparatide-SC" ], "class": "Synthetic 34 amino acid analog of parathyroid hormone related protein (PTHrP), a bone anabolic agent", "one_liner": "FDA approved daily osteoporosis injection that cut new spine fractures by 86% versus placebo (a dummy injection) in the 2,463 patient ACTIVE trial.", "summary": "Abaloparatide is a lab-made version of parathyroid hormone related protein that, injected daily, stimulates new bone formation; it was FDA approved as Tymlos in 2017 for postmenopausal women with osteoporosis (thin, fragile bones) at high fracture risk and in 2022 for men. In the 18 month ACTIVE trial of 2,463 women, 80 micrograms daily reduced new vertebral (spine) fractures from 4.22% to 0.58% and nonvertebral fractures (breaks elsewhere in the skeleton) by 43% versus placebo, with less hypercalcemia (too much calcium in the blood) than teriparatide. It is a prescription drug and is not compounded (custom-made by pharmacies).", "mechanism": "Abaloparatide is a selective activator of the PTH1 receptor that preferentially binds the transient RG conformation, producing a shorter signaling burst than teriparatide. Daily pulses stimulate osteoblast bone formation with a smaller rise in bone resorption and serum calcium. Bone density rises fastest in the first 6 months, and treatment is followed by an antiresorptive to preserve the gain.", "evidence_grade": "human_rct", "evidence_summary": "One large placebo and active controlled RCT plus an extension. ACTIVE (Miller 2016, n = 2,463): new vertebral fractures 0.58% with abaloparatide versus 4.22% with placebo (relative risk reduction 86%) and 0.84% with open label teriparatide; nonvertebral fractures 2.7% versus 4.7% (hazard ratio 0.57); hypercalcemia 3.4% versus 6.4% with teriparatide. ACTIVExtend (Cosman 2017): 18 months of abaloparatide followed by 6 months of alendronate kept vertebral fracture risk reduction at 87% versus the placebo to alendronate arm.", "human_evidence": "ACTIVE: 2,463 postmenopausal women with osteoporosis randomized to abaloparatide 80 ug daily, placebo, or open label teriparatide 20 ug daily for 18 months. New morphometric vertebral fractures: 0.58% abaloparatide, 4.22% placebo, 0.84% teriparatide. Nonvertebral fractures: 2.7% versus 4.7% placebo (hazard ratio 0.57, 95% CI 0.32 to 1.00). Lumbar spine BMD rose 11.2% versus 0.6% placebo. ACTIVExtend: after switching all participants to alendronate for 6 months, cumulative new vertebral fracture incidence remained lower in the abaloparatide sequence (0.55% versus 4.4%). The 2022 male indication rested on a 228 patient BMD trial.", "animal_evidence": "Rats given abaloparatide for 2 years showed a dose dependent increase in osteosarcoma, as with teriparatide. No osteosarcoma has been observed in humans; FDA removed the boxed warning in December 2021 based on the human safety record. Monkey studies showed increased bone formation and strength.", "conditions": [], "literature_dosing": "FDA label (Tymlos, DailyMed): 80 mcg injected subcutaneously once daily into the periumbilical region of the abdomen, rotating the site daily, with supplemental calcium and vitamin D if dietary intake is inadequate. The first several doses are given where the patient can sit or lie down in case of orthostatic hypotension. The label notes safety and efficacy have not been evaluated beyond 2 years of treatment. The ACTIVE trial used the same 80 mcg daily dose.", "routes": [ "Subcutaneous injection once daily (prefilled pen)" ], "side_effects": [ "Hypercalciuria (11%) and hypercalcemia (3.4% versus 0.4% placebo in ACTIVE)", "Dizziness (10%), nausea (8%), headache (8%), palpitations (5%)", "Orthostatic hypotension, usually within 4 hours of injection", "Injection site redness and pain", "Osteosarcoma in rats at high lifetime doses; boxed warning removed in 2021 after no human signal" ], "interactions": [ "Digoxin: abaloparatide induced hypercalcemia may increase digoxin toxicity", "Concurrent bisphosphonates or denosumab blunt the anabolic response; sequential use is standard", "No formal drug interaction studies beyond these" ], "contraindications": [ "Hypersensitivity to abaloparatide", "Pre-existing hypercalcemia, primary hyperparathyroidism, or hypercalcemic disorders", "Bone metastases, skeletal malignancy, Paget disease, prior skeletal radiation, or open epiphyses (higher baseline osteosarcoma risk, per label)", "Pregnancy and breastfeeding" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Tymlos in April 2017 for postmenopausal women with osteoporosis at high risk of fracture, with an expanded indication for men with osteoporosis in December 2022. In December 2021 FDA approved removal of the boxed warning for osteosarcoma and the 2 year cumulative use limit. Because an approved product exists, compounding is not permitted except for a documented patient specific need. No generic is available as of the last verified date.", "typical_cost": "List price roughly 2,000 to 3,000 USD per month. Most commercial plans and Medicare Part D cover it with prior authorization; a manufacturer copay program is available for commercially insured patients.", "access_path": [ "Prescription from a licensed provider filled at a specialty or retail pharmacy.", "Prior authorization typically requires a prior fragility fracture, very low bone density, or intolerance to other agents.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is abaloparatide (Tymlos) FDA approved, and what is it used for?", "a": "Yes. The Tymlos label covers two uses: treatment of postmenopausal women with osteoporosis (bones thin and fragile enough to break easily) at high risk for fracture (a history of osteoporotic fracture or multiple risk factors) or who have failed or cannot tolerate other osteoporosis therapy, and treatment to increase bone density in men with osteoporosis at high risk for fracture on the same terms. It was approved in 2017, with the men's indication added in 2022. It is prescription only.", "source_ids": [ "fda-tymlos-label" ] }, { "q": "How much does abaloparatide reduce fractures?", "a": "In the ACTIVE trial of 2,463 postmenopausal women, 18 months of abaloparatide 80 ug daily reduced new vertebral fractures from 4.22% on placebo to 0.58%, an 86% relative reduction, and nonvertebral fractures from 4.7% to 2.7%. When followed by 6 months of alendronate in ACTIVExtend, the vertebral fracture reduction was maintained at 87%.", "source_ids": [ "active-2016", "activextend-2017" ] }, { "q": "What are the side effects of abaloparatide?", "a": "The most common in ACTIVE were high urine calcium (11%), dizziness (10%), nausea (8%), headache (8%), and palpitations (5%). Blood calcium rose above normal in 3.4% of patients versus 6.4% on teriparatide. Orthostatic dizziness can occur within hours of injection, so the first doses are taken where the person can sit or lie down.", "source_ids": [ "active-2016", "fda-tymlos-label" ] }, { "q": "Does abaloparatide cause bone cancer?", "a": "Rats given abaloparatide for 2 years developed osteosarcoma in a dose dependent way, which produced a boxed warning at approval. No case has been linked to the drug in humans, and in December 2021 FDA removed the boxed warning and the 2 year use limit. People with Paget disease, prior bone radiation, or open growth plates are still advised to avoid it.", "source_ids": [ "fda-tymlos-label" ] }, { "q": "What is the abaloparatide (Tymlos) dose on the FDA label?", "a": "80 mcg injected under the skin of the lower abdomen once a day from a prefilled pen, rotating the site every day, with calcium and vitamin D if diet falls short. The label advises giving the first several doses sitting or lying down because of orthostatic hypotension, and states that safety and efficacy were not studied beyond 2 years. In the trials, treatment was followed by an antiresorptive such as alendronate to hold the bone gain.", "source_ids": [ "fda-tymlos-label", "activextend-2017" ] }, { "q": "How much does abaloparatide cost?", "a": "Roughly 2,000 to 3,000 USD per month at list price, with no generic. Insurance including Medicare Part D usually covers it after prior authorization, and a manufacturer copay program exists for commercially insured patients. Prices were checked on the last verified date.", "source_ids": [ "fda-tymlos-label" ] }, { "q": "Is abaloparatide banned by WADA?", "a": "No. PTH and PTHrP analogs are not named on the WADA Prohibited List. Athletes should confirm with their anti-doping organization since the list changes annually.", "source_ids": [ "wada-list" ] }, { "q": "Abaloparatide vs teriparatide: which is better?", "a": "In ACTIVE, abaloparatide and open label teriparatide had similar vertebral fracture rates (0.58% versus 0.84%), abaloparatide had fewer nonvertebral fractures numerically, and abaloparatide caused about half as much hypercalcemia (3.4% versus 6.4%). The trial was not designed to prove one superior on fractures. Teriparatide has generics and a longer track record; abaloparatide can be stored at room temperature after first use.", "source_ids": [ "active-2016", "fda-tymlos-label" ] } ], "studies": [ { "pmid": "27533157", "title": "Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE)", "year": 2016, "design": "Randomized, double blind, placebo controlled trial with open label teriparatide arm, 18 months", "n": 2463, "population": "Postmenopausal women aged 49 to 86 with osteoporosis", "outcome": "New vertebral fractures 0.58% abaloparatide versus 4.22% placebo (86% relative reduction); nonvertebral fractures hazard ratio 0.57; hypercalcemia 3.4% versus 6.4% with teriparatide", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27533157/" }, { "pmid": "28160873", "title": "Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: results of the ACTIVExtend trial", "year": 2017, "design": "Open label extension of ACTIVE with alendronate in both arms, 6 months", "population": "ACTIVE participants from the abaloparatide and placebo arms", "outcome": "Cumulative new vertebral fracture incidence 0.55% in the abaloparatide to alendronate sequence versus 4.4% in placebo to alendronate (87% relative reduction)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/28160873/" } ], "sources": [ { "id": "active-2016", "type": "pubmed", "title": "Miller PD et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 2016 (ACTIVE)", "url": "https://pubmed.ncbi.nlm.nih.gov/27533157/", "pmid": "27533157", "year": 2016 }, { "id": "activextend-2017", "type": "pubmed", "title": "Cosman F et al. Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: results of the ACTIVExtend trial. Mayo Clin Proc 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28160873/", "pmid": "28160873", "year": 2017 }, { "id": "fda-tymlos-label", "type": "fda", "title": "FDA prescribing information for Tymlos (abaloparatide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=712143d9-e21e-4013-bb3b-3426a21060a8", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "teriparatide", "calcitonin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Abaloparatide (Tymlos): uses, side effects, and dosing", "description": "Tymlos is abaloparatide, a daily bone-building injection for osteoporosis at high fracture risk. FDA-approved uses, label dose, side effects, and cost.", "h1": "Abaloparatide (Tymlos)" } }, { "slug": "octreotide", "name": "Octreotide", "aliases": [ "Sandostatin", "Sandostatin LAR", "Mycapssa", "Bynfezia Pen", "SMS 201-995", "Octreotide acetate" ], "class": "Synthetic cyclic octapeptide analog of somatostatin (somatostatin receptor 2 and 5 agonist)", "one_liner": "FDA approved since 1988 for acromegaly and carcinoid syndrome; the randomized PROMID trial showed it slows midgut neuroendocrine tumor growth (HR 0.34).", "summary": "Octreotide is an eight amino acid somatostatin analog, a lab-made version of the hormone that switches off growth hormone and many gut hormones, that has been FDA approved since 1988 to control growth hormone excess in acromegaly and the flushing and diarrhea of carcinoid and VIPoma syndromes, which are caused by hormone-producing tumors. It normalizes growth hormone or IGF-1 in roughly half to two thirds of acromegaly patients, and in the PROMID trial it lengthened time to tumor progression (growth) in metastatic midgut neuroendocrine tumors, hormone-producing small bowel tumors that have spread, from 6.0 to 14.3 months (hazard ratio 0.34). It is available as short acting injection, monthly depot (slow release injection), and an oral capsule, all by prescription.", "mechanism": "Octreotide binds somatostatin receptors, most strongly subtypes 2 and 5, on pituitary somatotrophs, neuroendocrine tumor cells, and gut endocrine cells. Receptor activation lowers cyclic AMP and calcium influx, suppressing secretion of growth hormone, glucagon, insulin, gastrin, VIP, serotonin, and other gut peptides, and slows tumor cell proliferation through phosphatase activation. Its half life of about 100 minutes is far longer than native somatostatin's 2 to 3 minutes.", "evidence_grade": "human_rct", "evidence_summary": "Decades of trials. A 2005 meta-analysis of long acting somatostatin analog trials in acromegaly found octreotide LAR normalized growth hormone in about 57% and IGF-1 in about 67% of patients, better in patients preselected as responders. PROMID (n = 85) was the first placebo controlled RCT showing antiproliferative effect in neuroendocrine tumors: median time to progression 14.3 versus 6.0 months, hazard ratio 0.34 (95% CI 0.20 to 0.59). Symptom control in carcinoid syndrome is supported by the original approval trials summarized in the 1996 NEJM review.", "human_evidence": "Freda 2005: meta-analysis of 44 studies of long acting somatostatin analogs in acromegaly; octreotide LAR achieved growth hormone control in about 57% and IGF-1 normalization in about 67% of patients overall. Rinke 2009 (PROMID): 85 treatment naive patients with metastatic well differentiated midgut neuroendocrine tumors randomized to octreotide LAR 30 mg monthly or placebo; median time to tumor progression 14.3 versus 6.0 months, hazard ratio 0.34; stable disease at 6 months in 66.7% versus 37.2%. Lamberts 1996 reviews the controlled trials that established symptom control of carcinoid syndrome flushing and diarrhea.", "animal_evidence": "Rodent and cell studies established receptor subtype selectivity, inhibition of hormone secretion, and antiproliferative signaling through somatostatin receptor 2. Animal toxicology showed no carcinogenicity signal relevant to the approved doses.", "conditions": [], "literature_dosing": "FDA labels (DailyMed). Sandostatin injection, subcutaneous or intravenous: acromegaly, 50 mcg three times daily for the first 2 weeks, most commonly 100 mcg three times daily for maintenance, up to 500 mcg three times daily; carcinoid tumors, 100 to 600 mcg a day in two to four divided doses for the first 2 weeks; VIPomas, 200 to 300 mcg a day in two to four divided doses for the first 2 weeks. Sandostatin LAR Depot, intragluteal every 4 weeks in patients who responded to and tolerated the injection: acromegaly, 20 mg every 4 weeks for 3 months, then adjusted between 10 and 40 mg; carcinoid tumors and VIPomas, 20 mg every 4 weeks for 2 months, then adjusted; 10 mg starting dose on dialysis or with cirrhosis. Mycapssa capsules, acromegaly maintenance after response to octreotide or lanreotide: 20 mg twice daily on an empty stomach, increased in 20 mg steps to a maximum of 80 mg a day.", "routes": [ "Subcutaneous injection two to four times daily (Sandostatin, Bynfezia)", "Intramuscular depot every 4 weeks (Sandostatin LAR)", "Oral delayed release capsule (Mycapssa)", "Intravenous infusion (hospital use, for example variceal bleeding off label)" ], "side_effects": [ "Diarrhea, nausea, abdominal pain, and steatorrhea (up to 30 to 60% in acromegaly trials, usually easing over weeks)", "Gallstones or biliary sludge (reported in up to about half of patients on long term treatment, mostly asymptomatic)", "Hyperglycemia or hypoglycemia from suppressed insulin and glucagon", "Bradycardia and conduction abnormalities", "Hypothyroidism with long term use", "Injection site pain (depot)", "Vitamin B12 deficiency with prolonged use" ], "interactions": [ "Insulin and oral antidiabetic drugs: octreotide alters glucose regulation and doses may need adjustment", "Cyclosporine: octreotide reduces cyclosporine absorption", "Beta blockers and calcium channel blockers: additive bradycardia", "Bromocriptine: octreotide increases bromocriptine bioavailability", "Drugs metabolized by CYP3A4 with a narrow therapeutic index: octreotide may slow their clearance", "Lutetium Lu 177 dotatate: the Sandostatin label says to stop short acting octreotide at least 24 hours before each dose" ], "contraindications": [ "Hypersensitivity to octreotide", "Use with caution in diabetes, gallbladder disease, cardiac conduction disease, and hypothyroidism", "Pregnancy: limited data, use only if clearly needed" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Sandostatin injection in 1988 (acromegaly, carcinoid tumors, VIPomas), Sandostatin LAR depot in 1998, Bynfezia Pen in 2020, and Mycapssa oral capsules in 2020 for acromegaly. Generic octreotide injection and generic depot products are available. Compounding is limited to patient specific needs because approved products exist.", "typical_cost": "Generic subcutaneous octreotide runs roughly 200 to 800 USD per month at cash prices depending on dose. Sandostatin LAR lists at roughly 4,000 to 8,000 USD per monthly injection, with generic depot products somewhat lower. Insurance and Medicare Part B or D typically cover it for approved indications.", "access_path": [ "Prescription from an endocrinologist, oncologist, or gastroenterologist filled at a specialty pharmacy, or administered in clinic for the depot.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is octreotide (Sandostatin) FDA approved, and what is it used for?", "a": "Yes, since 1988. The Sandostatin label covers acromegaly (excess growth hormone in adults) when surgery, pituitary irradiation, and bromocriptine have not worked or cannot be used, the severe diarrhea and flushing of metastatic carcinoid tumors (hormone-producing tumors that have spread), and the watery diarrhea of VIP secreting tumors (VIPomas). The monthly Sandostatin LAR Depot covers the same three uses in patients who responded to the injection, and the oral capsule Mycapssa covers acromegaly maintenance. The label notes that effects on tumor size were not shown in its trials. Generics exist; it is prescription only.", "source_ids": [ "fda-sandostatin-label", "fda-sandostatin-lar-label", "fda-mycapssa-label" ] }, { "q": "Does octreotide work for acromegaly?", "a": "For most patients, partly or fully. A 2005 meta-analysis of long acting somatostatin analog trials found octreotide LAR normalized growth hormone in about 57% of patients and IGF-1 in about 67%, with higher rates in patients known to respond to short acting octreotide. Tumor shrinkage occurs in a subset.", "source_ids": [ "freda-2005", "lamberts-1996" ] }, { "q": "Does octreotide slow neuroendocrine tumors?", "a": "Yes for midgut tumors. In the PROMID trial, 85 patients with metastatic well differentiated midgut neuroendocrine tumors were randomized to octreotide LAR 30 mg monthly or placebo; median time to progression was 14.3 versus 6.0 months (hazard ratio 0.34), and 66.7% versus 37.2% had stable disease at 6 months. Overall survival did not differ, partly because placebo patients crossed over.", "source_ids": [ "promid-2009" ] }, { "q": "What are the side effects of octreotide?", "a": "Gastrointestinal effects dominate early: loose stools, nausea, cramping, and fatty stools. Gallstones or sludge develop in a large share of long term users, usually without symptoms. Blood sugar can go up or down, heart rate can slow, and thyroid function can fall over time. The depot causes injection site pain.", "source_ids": [ "fda-sandostatin-label", "lamberts-1996" ] }, { "q": "What is the octreotide (Sandostatin) dose on the FDA label?", "a": "Acromegaly starts at 50 mcg under the skin three times daily, usually maintained at 100 mcg three times daily and up to 500 mcg three times daily. Carcinoid tumors start at 100 to 600 mcg a day and VIPomas at 200 to 300 mcg a day, in two to four divided doses. Responders can switch to Sandostatin LAR Depot, 20 mg into the buttock every 4 weeks and then adjusted (10 to 40 mg in acromegaly). Mycapssa capsules start at 20 mg twice daily, up to 80 mg a day.", "source_ids": [ "fda-sandostatin-label", "fda-sandostatin-lar-label", "fda-mycapssa-label" ] }, { "q": "How much does octreotide cost?", "a": "Generic subcutaneous vials cost roughly 200 to 800 USD per month at cash prices. The monthly depot lists at roughly 4,000 to 8,000 USD per injection, with generic depots lower. Insurance, including Medicare, generally covers it for approved diagnoses. Prices were checked on the last verified date.", "source_ids": [ "fda-sandostatin-label" ] }, { "q": "Is octreotide banned by WADA?", "a": "No. Somatostatin analogs are not on the WADA Prohibited List. Because octreotide suppresses growth hormone it has no doping rationale; athletes should still confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Octreotide vs lanreotide: what is the difference?", "a": "Both are somatostatin analogs with similar receptor profiles, efficacy in acromegaly, and side effects. Octreotide comes in short acting, depot, and oral forms; lanreotide is a deep subcutaneous depot given every 4 weeks (or every 6 to 8 weeks in stable acromegaly) that patients can self inject. Lanreotide has the larger antiproliferative trial (CLARINET, pancreatic and intestinal tumors); octreotide's PROMID trial covered midgut tumors only.", "source_ids": [ "promid-2009", "freda-2005" ] } ], "studies": [ { "pmid": "19704057", "title": "Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group", "year": 2009, "design": "Randomized, double blind, placebo controlled trial", "n": 85, "population": "Treatment naive adults with metastatic well differentiated midgut neuroendocrine tumors", "outcome": "Median time to tumor progression 14.3 versus 6.0 months (hazard ratio 0.34, 95% CI 0.20 to 0.59); stable disease at 6 months 66.7% versus 37.2%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19704057/" }, { "pmid": "15886238", "title": "Long-acting somatostatin analog therapy of acromegaly: a meta-analysis", "year": 2005, "design": "Meta-analysis of 44 studies", "population": "Adults with acromegaly treated with octreotide LAR or lanreotide", "outcome": "Octreotide LAR normalized growth hormone in about 57% and IGF-1 in about 67% of patients; higher in preselected responders", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/15886238/" }, { "pmid": "8532003", "title": "Octreotide", "year": 1996, "design": "Narrative review", "population": "Clinical trials in acromegaly, carcinoid syndrome, VIPoma, and other endocrine tumors", "outcome": "Summarizes symptom control, hormone suppression, and side effects (gallstones, gastrointestinal effects) across the approval era trials", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/8532003/" } ], "sources": [ { "id": "promid-2009", "type": "pubmed", "title": "Rinke A et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID). J Clin Oncol 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19704057/", "pmid": "19704057", "year": 2009 }, { "id": "freda-2005", "type": "pubmed", "title": "Freda PU et al. Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15886238/", "pmid": "15886238", "year": 2005 }, { "id": "lamberts-1996", "type": "pubmed", "title": "Lamberts SW et al. Octreotide. N Engl J Med 1996", "url": "https://pubmed.ncbi.nlm.nih.gov/8532003/", "pmid": "8532003", "year": 1996 }, { "id": "fda-sandostatin-label", "type": "fda", "title": "FDA prescribing information for Sandostatin (octreotide acetate) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e2c9856-1836-49f0-9472-4dbeeb408f39", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-sandostatin-lar-label", "type": "fda", "title": "FDA prescribing information for Sandostatin LAR Depot (octreotide acetate), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0b7fe9e-7000-4b79-ba3b-291ce92c14f9", "year": 2025 }, { "id": "fda-mycapssa-label", "type": "fda", "title": "FDA prescribing information for Mycapssa (octreotide) delayed-release capsules, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58d80bc6-bdfb-4908-93e7-aace447c8d1a", "year": 2025 } ], "related": [ "lanreotide", "tesamorelin", "glucagon" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Octreotide (Sandostatin): uses, side effects, and dosing", "description": "Sandostatin is octreotide, a somatostatin analog for acromegaly, carcinoid syndrome, and VIPomas. FDA label uses and doses, LAR and oral forms, side effects.", "h1": "Octreotide (Sandostatin)" } }, { "slug": "lanreotide", "name": "Lanreotide", "aliases": [ "Somatuline Depot", "Somatuline Autogel", "Lanreotide acetate", "BIM 23014" ], "class": "Synthetic cyclic octapeptide analog of somatostatin (somatostatin receptor 2 and 5 agonist), long acting depot", "one_liner": "FDA approved monthly copy of the hormone somatostatin for acromegaly and neuroendocrine tumors; halved tumor progression risk in the CLARINET trial (HR 0.47).", "summary": "Lanreotide is an eight amino acid somatostatin analog, a lab-made version of the hormone that switches off growth hormone and many gut hormones, given as a deep slow release (depot) injection under the skin every 4 weeks. It is FDA approved for acromegaly (excess growth hormone in adults, 2007), gastroenteropancreatic neuroendocrine tumors (hormone-producing tumors of the gut and pancreas, 2014), and carcinoid syndrome (flushing and diarrhea caused by such tumors, 2017). In the CLARINET trial of 204 patients with nonfunctioning enteropancreatic neuroendocrine tumors, lanreotide 120 mg monthly reduced the risk of progression (tumor growth) or death by 53% versus placebo (hazard ratio 0.47), with median progression free survival, the typical time before tumor growth, not reached versus 18 months. It is a prescription drug; a generic depot has been available since 2021.", "mechanism": "Lanreotide binds somatostatin receptors 2 and 5 on pituitary somatotrophs and neuroendocrine tumor cells, suppressing growth hormone, IGF-1, and gut hormone secretion and slowing tumor proliferation through receptor mediated phosphatase activation and reduced growth factor signaling. The depot formulation is a supersaturated gel that releases drug over about 4 weeks.", "evidence_grade": "human_rct", "evidence_summary": "CLARINET (n = 204) is the key randomized trial: progression free survival hazard ratio 0.47 (95% CI 0.30 to 0.73) for lanreotide 120 mg every 4 weeks versus placebo in metastatic or locally advanced nonfunctioning grade 1 or 2 enteropancreatic neuroendocrine tumors with Ki-67 under 10%. In acromegaly, the 2005 meta-analysis of long acting analog trials found lanreotide normalized growth hormone and IGF-1 in roughly half of patients, similar to octreotide.", "human_evidence": "Caplin 2014 (CLARINET): 204 patients randomized to lanreotide 120 mg or placebo every 28 days for 96 weeks; median progression free survival not reached with lanreotide versus 18.0 months with placebo, hazard ratio 0.47; estimated progression free survival at 24 months 65.1% versus 33.0%; overall survival did not differ. Freda 2005: pooled analysis of long acting somatostatin analog studies in acromegaly, in which lanreotide achieved growth hormone control in about 48% and IGF-1 normalization in about 47% of patients. The carcinoid syndrome indication rested on the ELECT trial (not cited here) showing fewer rescue octreotide doses.", "animal_evidence": "Preclinical work characterized receptor binding and hormone suppression in rodent and pituitary cell models and established the sustained release pharmacokinetics of the depot. No carcinogenicity signal relevant to approved dosing.", "conditions": [], "literature_dosing": "FDA label (Somatuline Depot, DailyMed; deep subcutaneous injection in the superior external quadrant of the buttock, given by a healthcare provider): acromegaly, 90 mg every 4 weeks for 3 months, then 120 mg if growth hormone or IGF-1 stays uncontrolled, 60 mg if growth hormone is 1 ng/mL or less with normal IGF-1, or 90 mg otherwise; patients controlled on 60 or 90 mg may be considered for 120 mg every 6 or 8 weeks. Gastroenteropancreatic neuroendocrine tumors: 120 mg every 4 weeks. Carcinoid syndrome: 120 mg every 4 weeks, with no extra dose for patients already treated for GEP-NETs. The label adjusts the acromegaly starting dose for renal or hepatic impairment.", "routes": [ "Deep subcutaneous injection every 4 weeks (prefilled syringe, can be self administered or given by a caregiver)" ], "side_effects": [ "Diarrhea (26% in CLARINET versus 9% placebo), abdominal pain (14%), nausea", "Cholelithiasis (10% in CLARINET versus 3%), biliary sludge", "Hyperglycemia or hypoglycemia", "Injection site pain, induration, or nodules", "Bradycardia", "Hypothyroidism with long term use", "Musculoskeletal pain and headache" ], "interactions": [ "Insulin and oral antidiabetic drugs: glucose control may shift and require dose changes", "Cyclosporine: lanreotide may reduce cyclosporine absorption", "Bradycardic drugs (beta blockers): additive slowing of heart rate", "Drugs cleared by CYP3A4 with narrow therapeutic index: possible reduced clearance" ], "contraindications": [ "Hypersensitivity to lanreotide or somatostatin analogs", "Use with caution in diabetes, gallbladder disease, cardiac conduction disease, and thyroid disease", "Pregnancy: limited data, use only if clearly needed" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Somatuline Depot in August 2007 for acromegaly, December 2014 for unresectable gastroenteropancreatic neuroendocrine tumors, and September 2017 for carcinoid syndrome. A generic lanreotide injection was approved in December 2021. Compounding is not permitted beyond patient specific exceptions because approved products exist.", "typical_cost": "Brand Somatuline Depot lists at roughly 6,000 to 9,000 USD per monthly injection; generic lanreotide is lower but still several thousand USD. Insurance and Medicare Part B or D typically cover it for approved indications, and a manufacturer assistance program exists.", "access_path": [ "Prescription from an endocrinologist or oncologist, dispensed by a specialty pharmacy or administered in clinic.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is lanreotide (Somatuline Depot) FDA approved, and what is it used for?", "a": "Yes. The Somatuline Depot label covers long term treatment of acromegaly (excess growth hormone in adults) when surgery or radiotherapy has failed or is not possible (approved 2007); unresectable (not removable by surgery), well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, which are hormone-producing tumors of the gut and pancreas, to improve progression free survival, the time before the tumor grows (2014); and carcinoid syndrome, the flushing and diarrhea these tumors can cause, where it reduces the need for short acting somatostatin analog rescue (2017). A generic lanreotide injection was approved in 2021. It is prescription only.", "source_ids": [ "fda-somatuline-label" ] }, { "q": "Does lanreotide slow neuroendocrine tumor growth?", "a": "Yes. In CLARINET, 204 patients with advanced nonfunctioning enteropancreatic neuroendocrine tumors received lanreotide 120 mg or placebo monthly for 96 weeks. The risk of progression or death fell by 53% (hazard ratio 0.47), and 65% of lanreotide patients versus 33% of placebo patients were progression free at 2 years. Median progression free survival was not reached on lanreotide versus 18 months on placebo.", "source_ids": [ "clarinet-2014" ] }, { "q": "Does lanreotide work for acromegaly?", "a": "For about half of patients. A 2005 meta-analysis of long acting somatostatin analog trials found lanreotide normalized growth hormone in about 48% and IGF-1 in about 47%, comparable to octreotide LAR when patient selection is accounted for. Patients who do not respond can be switched to other agents or combined with cabergoline or pegvisomant.", "source_ids": [ "freda-2005" ] }, { "q": "What are the side effects of lanreotide?", "a": "In CLARINET the most common were diarrhea (26% versus 9% on placebo), abdominal pain, and gallstones (10% versus 3%). Blood sugar changes, slow heart rate, injection site nodules, and low thyroid function can occur with long term use. Most gastrointestinal effects ease over the first months.", "source_ids": [ "clarinet-2014", "fda-somatuline-label" ] }, { "q": "What is the lanreotide (Somatuline Depot) dose on the FDA label?", "a": "A deep subcutaneous injection into the upper outer buttock, given by a healthcare provider. Acromegaly starts at 90 mg every 4 weeks for 3 months and is then adjusted to 60, 90, or 120 mg by growth hormone and IGF-1 levels; patients controlled on 60 or 90 mg may move to 120 mg every 6 or 8 weeks. Neuroendocrine tumors and carcinoid syndrome use 120 mg every 4 weeks.", "source_ids": [ "fda-somatuline-label" ] }, { "q": "How much does lanreotide cost?", "a": "Roughly 6,000 to 9,000 USD per monthly injection at brand list price, and somewhat less for the generic approved in 2021. Insurance including Medicare usually covers it for the approved indications, and manufacturer assistance exists. Prices were checked on the last verified date.", "source_ids": [ "fda-somatuline-label" ] }, { "q": "Is lanreotide banned by WADA?", "a": "No. Somatostatin analogs are not on the WADA Prohibited List and lanreotide lowers rather than raises growth hormone. Athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Lanreotide vs octreotide LAR: which is better?", "a": "They are considered interchangeable for acromegaly, with similar biochemical control rates and side effects. Lanreotide's advantages are self injection, a prefilled syringe, and extended dosing intervals for well controlled patients. Octreotide has a short acting form for titration and an oral capsule. For neuroendocrine tumors, lanreotide has the broader trial (CLARINET, pancreatic and intestinal), while octreotide's PROMID covered midgut tumors.", "source_ids": [ "clarinet-2014", "freda-2005" ] } ], "studies": [ { "pmid": "25014687", "title": "Lanreotide in metastatic enteropancreatic neuroendocrine tumors (CLARINET)", "year": 2014, "design": "Randomized, double blind, placebo controlled trial, 96 weeks", "n": 204, "population": "Adults with advanced, well or moderately differentiated, nonfunctioning, somatostatin receptor positive enteropancreatic neuroendocrine tumors (Ki-67 under 10%)", "outcome": "Progression free survival hazard ratio 0.47 (95% CI 0.30 to 0.73); median not reached versus 18.0 months; 24 month progression free rate 65.1% versus 33.0%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25014687/" }, { "pmid": "15886238", "title": "Long-acting somatostatin analog therapy of acromegaly: a meta-analysis", "year": 2005, "design": "Meta-analysis of 44 studies", "population": "Adults with acromegaly treated with lanreotide or octreotide LAR", "outcome": "Lanreotide normalized growth hormone in about 48% and IGF-1 in about 47% of patients", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/15886238/" } ], "sources": [ { "id": "clarinet-2014", "type": "pubmed", "title": "Caplin ME et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014 (CLARINET)", "url": "https://pubmed.ncbi.nlm.nih.gov/25014687/", "pmid": "25014687", "year": 2014 }, { "id": "freda-2005", "type": "pubmed", "title": "Freda PU et al. Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15886238/", "pmid": "15886238", "year": 2005 }, { "id": "fda-somatuline-label", "type": "fda", "title": "FDA prescribing information for Somatuline Depot (lanreotide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6e4a41fd-a753-4362-87ee-8cc56ed3660d", "year": 2024 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "octreotide", "tesamorelin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Lanreotide (Somatuline): uses, side effects, and dosing", "description": "Somatuline Depot is lanreotide, a monthly somatostatin analog for acromegaly, neuroendocrine tumors, and carcinoid syndrome. Label doses, side effects, cost.", "h1": "Lanreotide (Somatuline Depot)" } }, { "slug": "leuprolide", "name": "Leuprolide", "aliases": [ "Lupron", "Lupron Depot", "Eligard", "Fensolvi", "Camcevi", "Leuprorelin", "Leuprolide acetate" ], "class": "Synthetic nonapeptide GnRH (LHRH) agonist analog", "one_liner": "FDA approved since 1985; after a brief surge it shuts down testosterone or estrogen; standard therapy for prostate cancer, endometriosis, and early puberty.", "summary": "Leuprolide is a nine amino acid GnRH agonist, a lab-made version of the brain hormone that controls sex hormone production, that after an initial surge desensitizes the pituitary and drops testosterone or estrogen to castrate levels (as low as after surgical removal of the testes or ovaries) within 2 to 4 weeks. It has been FDA approved since 1985 and is a standard treatment for advanced prostate cancer, endometriosis, uterine fibroids (noncancerous growths in the womb), and central precocious puberty (puberty that starts too early). In the 1984 pivotal trial it matched diethylstilbestrol, an older estrogen drug, for prostate cancer response with fewer cardiovascular side effects, and adding flutamide extended median survival from 28.3 to 35.6 months in a 603 patient trial. It is prescription only and available as daily injections and 1 to 6 month depots (slow release injections).", "mechanism": "Leuprolide is a potent GnRH receptor agonist. Continuous exposure first stimulates then downregulates pituitary GnRH receptors, so LH and FSH secretion falls and gonadal production of testosterone or estradiol drops to castrate or postmenopausal levels after an initial 1 to 2 week flare. Hormone sensitive tissues such as prostate cancer, endometriosis implants, and fibroids regress. The effect reverses after treatment stops.", "evidence_grade": "human_rct", "evidence_summary": "Randomized trials across four decades. The Leuprolide Study Group 1984 trial (n = 199) found leuprolide equivalent to diethylstilbestrol for objective response in metastatic prostate cancer with less gynecomastia, nausea, and thromboembolism. Crawford 1989 (n = 603) found leuprolide plus flutamide extended median survival versus leuprolide alone (35.6 versus 28.3 months). Klotz 2008 (n = 610) used leuprolide 7.5 mg monthly as the comparator for degarelix and documented testosterone suppression below 0.5 ng/mL in 96.4% of patients from day 28 to day 364.", "human_evidence": "Leuprolide Study Group 1984: 199 men with previously untreated stage D2 prostate cancer randomized to leuprolide 1 mg subcutaneously daily or diethylstilbestrol 3 mg daily; objective response and 1 year survival were similar, with fewer cardiovascular and breast side effects on leuprolide. Crawford 1989: 603 men with stage D2 prostate cancer randomized to leuprolide plus flutamide or leuprolide plus placebo; median progression free survival 16.5 versus 13.9 months and median survival 35.6 versus 28.3 months. Klotz 2008: leuprolide 7.5 mg monthly comparator arm achieved sustained castration in 96.4% but with a testosterone surge in the first week and microsurges on reinjection. Endometriosis, fibroid, and pediatric indications rest on smaller controlled trials summarized in the labels.", "animal_evidence": "Preclinical rodent studies established GnRH receptor downregulation and reversible gonadal suppression. Rat carcinogenicity studies showed benign pituitary adenomas at high doses, a species specific finding not reproduced in humans over decades of use.", "conditions": [], "literature_dosing": "FDA labels (DailyMed). Advanced prostate cancer: Lupron Depot 7.5 mg intramuscularly every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks; Eligard 7.5 mg subcutaneously every month, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months; Camcevi 42 mg subcutaneously every 6 months. Endometriosis: Lupron Depot 3.75 mg intramuscularly monthly for up to 6 injections, or 11.25 mg every 3 months for up to 2 injections, alone or with daily 5 mg norethindrone acetate add back, and no more than 12 months in total with add back. Uterine fibroids with anemia: Lupron Depot 3.75 mg or 11.25 mg with iron therapy before surgery, when 3 months of hormonal suppression is needed. Central precocious puberty: Lupron Depot-Ped 7.5, 11.25, or 15 mg monthly by weight, 11.25 or 30 mg every 3 months, or 45 mg every 6 months, intramuscularly; Fensolvi 45 mg subcutaneously every 6 months from age 2. Depot strengths have different release profiles and are not interchangeable or additive.", "routes": [ "Intramuscular depot every 1, 3, 4, or 6 months (Lupron Depot)", "Subcutaneous depot every 1 to 6 months (Eligard, Fensolvi, Camcevi)", "Subcutaneous injection once daily (leuprolide acetate 1 mg)" ], "side_effects": [ "Hot flashes (most patients on prostate cancer doses)", "Testosterone flare in the first 1 to 2 weeks, which can worsen bone pain or urinary obstruction in metastatic prostate cancer", "Loss of libido and erectile dysfunction; vaginal dryness and mood changes in women", "Bone mineral density loss and fracture risk with prolonged use", "Weight gain, insulin resistance, and increased cardiovascular risk with long term androgen deprivation", "QT prolongation with long term androgen deprivation", "Injection site pain and sterile abscess (depot)", "Pituitary apoplexy (rare, reported after first dose in patients with pituitary adenoma)" ], "interactions": [ "QT prolonging drugs: additive risk during androgen deprivation", "Antidiabetic drugs: androgen deprivation worsens glucose control and doses may need adjustment", "Diagnostic tests: suppresses pituitary gonadal function tests during and for up to 3 months after treatment" ], "contraindications": [ "Pregnancy (may cause fetal harm; rule out before starting in women)", "Undiagnosed abnormal vaginal bleeding", "Hypersensitivity to GnRH agonists", "Use with caution in patients with spinal metastases or urinary obstruction where flare could cause compression, unless an antiandrogen covers the flare" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Lupron injection in April 1985 for advanced prostate cancer, with Lupron Depot (1989), Lupron Depot-Ped (1993), Eligard (2002), Fensolvi (2020), and Camcevi (2021) following for prostate cancer, endometriosis, fibroids, and central precocious puberty. Generic leuprolide injection is available. Compounding is limited to patient specific needs because approved products exist.", "typical_cost": "Lupron Depot 7.5 mg lists at roughly 2,000 to 2,500 USD per monthly injection and about 6,000 to 7,000 USD for the 3 month 22.5 mg depot; Eligard and generic leuprolide are lower. Insurance and Medicare Part B routinely cover it for cancer and other approved indications.", "access_path": [ "Prescription from a urologist, oncologist, gynecologist, or pediatric endocrinologist, usually administered in clinic.", "Fertility clinics prescribe low dose leuprolide off label for IVF protocols.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is leuprolide (Lupron Depot) FDA approved, and what is it used for?", "a": "Yes. Leuprolide products are FDA approved for advanced prostate cancer (Lupron Depot 7.5 to 45 mg, Eligard, Camcevi), for endometriosis and for anemia from uterine fibroids (noncancerous growths in the womb) before surgery (Lupron Depot 3.75 mg and 11.25 mg), and for central precocious puberty, puberty that starts too early, in children (Lupron Depot-Ped, Fensolvi). All are prescription only and given by a healthcare provider.", "source_ids": [ "fda-lupron-label", "fda-lupron-375-label", "fda-lupron-ped-label", "fda-eligard-label", "fda-fensolvi-label", "fda-camcevi-label" ] }, { "q": "Does leuprolide work for prostate cancer?", "a": "Yes. In the 1984 pivotal trial of 199 men with metastatic prostate cancer, leuprolide produced the same objective response and 1 year survival as diethylstilbestrol with fewer cardiovascular side effects, and it lowers testosterone to castrate levels in about 96% of men within 4 weeks. Adding the antiandrogen flutamide extended median survival from 28.3 to 35.6 months in a 603 patient trial.", "source_ids": [ "leuprolide-study-group-1984", "crawford-1989", "klotz-2008" ] }, { "q": "What are the side effects of leuprolide?", "a": "Hot flashes, loss of libido, erectile dysfunction, fatigue, weight gain, and bone loss are the expected effects of shutting down sex hormones. A testosterone flare in the first 1 to 2 weeks can temporarily worsen bone pain or urinary symptoms in men with metastatic cancer, which is why an antiandrogen is often given at the start. Long term androgen deprivation raises cardiovascular and diabetes risk.", "source_ids": [ "fda-lupron-label", "klotz-2008" ] }, { "q": "What is the leuprolide (Lupron Depot) dose on the FDA label?", "a": "For advanced prostate cancer, Lupron Depot is 7.5 mg every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks into muscle; Eligard uses the same strengths under the skin monthly to every 6 months, and Camcevi is 42 mg every 6 months. For endometriosis, Lupron Depot is 3.75 mg monthly or 11.25 mg every 3 months for a 6 month course. Children with central precocious puberty receive weight based Lupron Depot-Ped doses or Fensolvi 45 mg every 6 months. Strengths are not interchangeable.", "source_ids": [ "fda-lupron-label", "fda-eligard-label", "fda-camcevi-label", "fda-lupron-375-label", "fda-lupron-ped-label", "fda-fensolvi-label" ] }, { "q": "How much does leuprolide cost?", "a": "Lupron Depot lists at roughly 2,000 to 2,500 USD per monthly 7.5 mg injection and about 6,000 to 7,000 USD for the 3 month depot, with Eligard and generics lower. Insurance and Medicare Part B routinely cover it for approved indications. Prices were checked on the last verified date.", "source_ids": [ "fda-lupron-label" ] }, { "q": "Is leuprolide banned by WADA?", "a": "Yes for male athletes. The WADA Prohibited List section S2 prohibits GnRH and its analogs, including leuprorelin (leuprolide), in males at all times because they can be used to manipulate testosterone testing and recovery. A therapeutic use exemption is required for medical use.", "source_ids": [ "wada-list" ] }, { "q": "Leuprolide vs degarelix: what is the difference?", "a": "Leuprolide is a GnRH agonist and causes a testosterone surge for 1 to 2 weeks before suppression; degarelix is a GnRH antagonist and suppresses testosterone within 3 days without a flare. In the 610 patient head to head trial, castration was maintained through 1 year in 96.4% on leuprolide versus 97.2% to 98.3% on degarelix, but degarelix caused injection site reactions in about 40% of patients. Leuprolide has more depot options and a lower price.", "source_ids": [ "klotz-2008" ] }, { "q": "Why is leuprolide used in IVF and for kids?", "a": "In IVF, low dose leuprolide is used off label to prevent a premature LH surge or to trigger final egg maturation. In children, monthly or 3 monthly depots are FDA approved for central precocious puberty, where they pause puberty until an appropriate age; puberty resumes after stopping.", "source_ids": [ "fda-lupron-label" ] } ], "studies": [ { "pmid": "6436700", "title": "Leuprolide versus diethylstilbestrol for metastatic prostate cancer", "year": 1984, "design": "Randomized, open label, active comparator trial", "n": 199, "population": "Men with previously untreated stage D2 prostate cancer", "outcome": "Similar objective response and 1 year survival with leuprolide 1 mg daily versus diethylstilbestrol 3 mg daily, with fewer cardiovascular, breast, and gastrointestinal side effects", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/6436700/" }, { "pmid": "2503724", "title": "A controlled trial of leuprolide with and without flutamide in prostatic carcinoma", "year": 1989, "design": "Randomized, double blind, placebo controlled trial", "n": 603, "population": "Men with stage D2 prostate cancer", "outcome": "Leuprolide plus flutamide extended median progression free survival (16.5 versus 13.9 months) and median survival (35.6 versus 28.3 months) versus leuprolide plus placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/2503724/" }, { "pmid": "19035858", "title": "The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer", "year": 2008, "design": "Randomized, open label, active comparator trial, 12 months", "n": 610, "population": "Men with prostate cancer requiring androgen deprivation", "outcome": "Leuprolide 7.5 mg monthly maintained testosterone below 0.5 ng/mL from day 28 to 364 in 96.4% of patients, with an initial testosterone surge in the first week", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19035858/" } ], "sources": [ { "id": "leuprolide-study-group-1984", "type": "pubmed", "title": "The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med 1984", "url": "https://pubmed.ncbi.nlm.nih.gov/6436700/", "pmid": "6436700", "year": 1984 }, { "id": "crawford-1989", "type": "pubmed", "title": "Crawford ED et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 1989", "url": "https://pubmed.ncbi.nlm.nih.gov/2503724/", "pmid": "2503724", "year": 1989 }, { "id": "klotz-2008", "type": "pubmed", "title": "Klotz L et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/19035858/", "pmid": "19035858", "year": 2008 }, { "id": "fda-lupron-label", "type": "fda", "title": "FDA prescribing information for Lupron Depot (leuprolide acetate) for prostate cancer, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbc8f94e-7330-4465-05ad-16d64493a5dd", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (GnRH and its analogs in males)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-lupron-375-label", "type": "fda", "title": "FDA prescribing information for Lupron Depot 3.75 mg (leuprolide acetate), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00c486b0-bd7b-4898-834d-8c656e5e73cb", "year": 2025 }, { "id": "fda-lupron-ped-label", "type": "fda", "title": "FDA prescribing information for Lupron Depot-Ped (leuprolide acetate), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e99f47d2-da10-3127-ecb3-e5d942ae6e81", "year": 2025 }, { "id": "fda-eligard-label", "type": "fda", "title": "FDA prescribing information for Eligard (leuprolide acetate) injectable suspension, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc", "year": 2026 }, { "id": "fda-fensolvi-label", "type": "fda", "title": "FDA prescribing information for Fensolvi (leuprolide acetate) injectable suspension, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c311700-edf4-4f2a-a468-9875489a6cc7", "year": 2025 }, { "id": "fda-camcevi-label", "type": "fda", "title": "FDA prescribing information for Camcevi (leuprolide) injectable emulsion, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbff25e5-6fe8-4e44-b10a-8397b3349905", "year": 2026 } ], "related": [ "triptorelin", "degarelix", "gonadorelin", "hcg" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Leuprolide (Lupron Depot): uses, side effects, and dosing", "description": "Lupron Depot and Eligard are leuprolide, a GnRH agonist for prostate cancer, endometriosis, fibroids, and early puberty. FDA label doses and side effects.", "h1": "Leuprolide (Lupron Depot, Eligard)" } }, { "slug": "triptorelin", "name": "Triptorelin", "aliases": [ "Trelstar", "Triptodur", "Decapeptyl", "Triptorelin pamoate", "Triptorelin acetate", "D-Trp6-LHRH" ], "class": "Synthetic decapeptide GnRH (LHRH) agonist analog", "one_liner": "FDA approved depot shot that shuts off sex hormones, for advanced prostate cancer (2000) and early puberty (2017); matched leuprolide in a 284 patient trial.", "summary": "Triptorelin is a ten amino acid GnRH agonist, a lab-made version of the brain hormone that controls sex hormones, that suppresses testosterone to castrate levels (as low as after removal of the testes) after an initial flare, a brief rise, given as a 1, 3, or 6 month intramuscular depot (slow release injection into muscle). It is FDA approved as Trelstar for palliative treatment (symptom control, not cure) of advanced prostate cancer (2000) and as Triptodur for central precocious puberty, puberty that starts too early, in children 2 years and older (2017), and it is widely used abroad for endometriosis and IVF. In a 284 patient randomized trial it produced castration rates comparable to leuprolide at 9 months. It is prescription only and not compounded.", "mechanism": "Triptorelin is a GnRH receptor agonist with a D-tryptophan substitution at position 6 that resists degradation. Continuous exposure downregulates pituitary GnRH receptors, so LH and FSH fall and testosterone or estradiol drops to castrate or prepubertal levels within 2 to 4 weeks after a brief initial surge. In children with central precocious puberty it suppresses the premature pituitary gonadal axis until treatment stops.", "evidence_grade": "human_rct", "evidence_summary": "Heyns 2003 (n = 284) randomized men with advanced prostate cancer to triptorelin pamoate 3.75 mg or leuprolide 7.5 mg monthly for 9 months; both achieved castrate testosterone in the large majority of patients with comparable maintenance of castration through month 9. The pediatric indication rests on an open label single arm trial in which the 6 month depot suppressed LH to prepubertal levels in most children at month 6. Other indications rely on trials conducted outside the US and summarized in the labels.", "human_evidence": "Heyns 2003: 284 men with advanced prostate cancer randomized to monthly triptorelin pamoate or leuprolide acetate for 9 months. Castrate testosterone (50 ng/dL or below) was achieved by day 29 in a slightly smaller proportion on triptorelin, but maintenance of castration through month 9 was comparable, and 9 month survival was similar. Triptodur approval was based on a 44 patient open label trial in children with central precocious puberty in which peak stimulated LH fell to prepubertal levels in the large majority by month 6 and was maintained at month 12. The endometriosis and fertility uses common in Europe rest on trials of non US formulations.", "animal_evidence": "Preclinical studies established GnRH receptor agonism, reversible gonadal suppression, and depot pharmacokinetics. Rat carcinogenicity studies showed pituitary adenomas at high doses, a species specific finding shared by other GnRH agonists.", "conditions": [], "literature_dosing": "FDA labels (DailyMed). Trelstar, advanced prostate cancer: a single intramuscular injection in either buttock of 3.75 mg every 4 weeks, 11.25 mg every 12 weeks, or 22.5 mg every 24 weeks; the strengths are not additive. Triptodur, central precocious puberty in children 2 and older: 22.5 mg as a single intramuscular injection every 24 weeks, given by a healthcare provider, with LH or sex steroid levels checked 1 to 2 months after starting.", "routes": [ "Intramuscular depot every 4, 12, or 24 weeks (Trelstar)", "Intramuscular depot every 24 weeks (Triptodur, pediatric)" ], "side_effects": [ "Hot flashes (the most common effect in men, over half of patients)", "Testosterone flare in the first 1 to 2 weeks, which can worsen bone pain, ureteral obstruction, or spinal cord compression in metastatic prostate cancer", "Erectile dysfunction, decreased libido, fatigue", "Bone density loss with prolonged use", "Hyperglycemia, weight gain, and increased cardiovascular risk with long term androgen deprivation", "QT prolongation", "Injection site pain; in children, injection site reactions and transient vaginal bleeding after the first dose", "Anaphylaxis and pituitary apoplexy (rare)" ], "interactions": [ "QT prolonging drugs: additive risk during androgen deprivation", "Hyperprolactinemic drugs: high prolactin reduces pituitary GnRH receptors and may blunt the effect", "Antidiabetic drugs: glucose control may worsen and require adjustment", "Interferes with pituitary gonadal diagnostic tests during and after treatment" ], "contraindications": [ "Pregnancy (fetal harm) and breastfeeding", "Hypersensitivity to triptorelin, GnRH, or other GnRH analogs", "Use with caution where flare could cause spinal cord compression or urinary obstruction unless an antiandrogen is given" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Trelstar (triptorelin pamoate) in June 2000 for palliative treatment of advanced prostate cancer, with 3 month and 6 month depots added later, and as Triptodur in June 2017 for central precocious puberty in children 2 years and older. Triptorelin is approved in Europe for endometriosis, fibroids, breast cancer, and assisted reproduction, uses that are off label in the US. Compounding is not permitted beyond patient specific needs because approved products exist.", "typical_cost": "Trelstar lists at roughly 1,500 to 2,500 USD per monthly 3.75 mg injection and roughly 4,500 to 7,000 USD for the 3 month 11.25 mg depot. Insurance and Medicare Part B typically cover it for prostate cancer; Triptodur for children is covered with prior authorization.", "access_path": [ "Prescription from a urologist, oncologist, or pediatric endocrinologist, administered in clinic as a depot injection.", "Fertility clinics prescribe triptorelin off label (often imported or compounded acetate) as an IVF trigger.", "Not available through telehealth peptide clinics." ], "faqs": [ { "q": "Is triptorelin FDA approved, and what is it used for?", "a": "Yes. The Trelstar label (approved 2000) covers the treatment of advanced prostate cancer, and the Triptodur label (approved 2017) covers central precocious puberty, puberty that starts too early, in children 2 years and older. Both are prescription only and given as a depot (slow release) injection in a clinic.", "source_ids": [ "fda-trelstar-label", "fda-triptodur-label" ] }, { "q": "Does triptorelin work as well as leuprolide for prostate cancer?", "a": "Comparably. In a 284 patient randomized trial, monthly triptorelin 3.75 mg and leuprolide 7.5 mg both brought testosterone to castrate levels in the large majority of men, with similar maintenance of castration and 9 month survival. Triptorelin was slightly slower to reach castration at day 29 in that trial.", "source_ids": [ "heyns-2003" ] }, { "q": "What are the side effects of triptorelin?", "a": "The expected effects of low testosterone: hot flashes, loss of libido, erectile dysfunction, fatigue, weight gain, and bone loss over time. A testosterone flare in the first 1 to 2 weeks can temporarily worsen bone pain or urinary obstruction in men with metastatic cancer, so an antiandrogen is often given at the start. Long term use raises diabetes and cardiovascular risk and can prolong the QT interval.", "source_ids": [ "fda-trelstar-label", "heyns-2003" ] }, { "q": "What is the triptorelin (Trelstar) dose on the FDA label?", "a": "Trelstar for advanced prostate cancer is one intramuscular injection of 3.75 mg every 4 weeks, 11.25 mg every 12 weeks, or 22.5 mg every 24 weeks. Triptodur for central precocious puberty is 22.5 mg every 24 weeks. A clinician gives every dose, and the strengths are not interchangeable.", "source_ids": [ "fda-trelstar-label", "fda-triptodur-label" ] }, { "q": "How much does triptorelin cost?", "a": "Roughly 1,500 to 2,500 USD per monthly 3.75 mg Trelstar injection and 4,500 to 7,000 USD for the 3 month depot at list price. Insurance and Medicare Part B cover it for prostate cancer, and Triptodur is covered for precocious puberty with prior authorization. Prices were checked on the last verified date.", "source_ids": [ "fda-trelstar-label" ] }, { "q": "Is triptorelin banned by WADA?", "a": "Yes for male athletes. WADA's section S2 names triptorelin among the GnRH analogs prohibited in males at all times. A therapeutic use exemption is required for medical use.", "source_ids": [ "wada-list" ] }, { "q": "Why do IVF clinics use triptorelin?", "a": "A single low dose of a GnRH agonist such as triptorelin triggers an LH surge that matures eggs before retrieval, and it lowers the risk of ovarian hyperstimulation syndrome compared with an HCG trigger. This use is off label in the US and relies on non US formulations or compounded triptorelin acetate.", "source_ids": [ "fda-trelstar-label" ] }, { "q": "Triptorelin vs leuprolide vs degarelix: how do they differ?", "a": "Triptorelin and leuprolide are GnRH agonists with a testosterone flare and comparable castration rates; degarelix is a GnRH antagonist with no flare and suppression within 3 days, at the cost of frequent injection site reactions. Triptorelin has the pediatric 6 month depot; leuprolide has more formulations; degarelix is preferred when a flare would be dangerous.", "source_ids": [ "heyns-2003" ] } ], "studies": [ { "pmid": "12887472", "title": "Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer", "year": 2003, "design": "Randomized, open label, active comparator trial, 9 months", "n": 284, "population": "Men with advanced prostate cancer", "outcome": "Comparable maintenance of castrate testosterone through 9 months and similar 9 month survival; triptorelin reached castration slightly more slowly by day 29", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/12887472/" } ], "sources": [ { "id": "heyns-2003", "type": "pubmed", "title": "Heyns CF et al. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int 2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12887472/", "pmid": "12887472", "year": 2003 }, { "id": "fda-trelstar-label", "type": "fda", "title": "FDA prescribing information for Trelstar (triptorelin pamoate for injectable suspension), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1b84d62-a369-a4b7-5c41-dd1f553a18f3", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (GnRH and its analogs in males)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-triptodur-label", "type": "fda", "title": "FDA prescribing information for Triptodur (triptorelin) for extended-release injectable suspension, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f41380e7-b830-432d-a5f5-a872932f107e", "year": 2025 } ], "related": [ "leuprolide", "degarelix", "gonadorelin", "hcg" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Triptorelin (Trelstar): uses, side effects, and dosing", "description": "Trelstar and Triptodur are triptorelin, a GnRH agonist for advanced prostate cancer and central precocious puberty. FDA label doses, side effects, and cost.", "h1": "Triptorelin (Trelstar, Triptodur)" } }, { "slug": "degarelix", "name": "Degarelix", "aliases": [ "Firmagon", "Degarelix acetate", "FE200486" ], "class": "Synthetic decapeptide GnRH (LHRH) receptor antagonist", "one_liner": "FDA approved GnRH blocker for advanced prostate cancer: castrate testosterone in 3 days with no flare, held in 97 to 98% at 1 year in a 610 patient trial.", "summary": "Degarelix is a ten amino acid GnRH receptor antagonist: it blocks the pituitary's receptor for GnRH, the brain hormone that switches on testosterone production, so testosterone falls to castrate levels (as low as after removal of the testes) within 3 days without the surge seen with agonists (drugs that first stimulate, then shut down, the same receptor) such as leuprolide. It has been FDA approved as Firmagon since December 2008 for advanced prostate cancer. In the 610 patient pivotal trial (the main trial behind approval), 97.2 to 98.3% of men on degarelix maintained castrate testosterone from day 28 through 1 year versus 96.4% on leuprolide, at the cost of injection site reactions in about 40%. It is prescription only and given as a monthly injection under the skin.", "mechanism": "Degarelix competitively blocks GnRH receptors on pituitary gonadotrophs, immediately suppressing LH and FSH release and therefore testicular testosterone production. Because it does not stimulate the receptor, there is no initial testosterone surge and no microsurge on repeat dosing. The subcutaneous depot forms a gel that releases drug over about a month.", "evidence_grade": "human_rct", "evidence_summary": "One large randomized active controlled phase III trial. Klotz 2008 (n = 610): degarelix 240 mg loading dose followed by 80 mg or 160 mg monthly versus leuprolide 7.5 mg monthly for 12 months. Testosterone was 0.5 ng/mL or below from day 28 through day 364 in 97.2% (80 mg) and 98.3% (160 mg) versus 96.4% on leuprolide, meeting noninferiority. By day 3, 96% of degarelix patients were castrate versus none on leuprolide, and PSA fell faster. Injection site reactions occurred in about 40% versus under 1%.", "human_evidence": "Klotz 2008: 610 men with prostate cancer requiring androgen deprivation. Castration maintenance day 28 to 364: 97.2% with degarelix 240/80 mg, 98.3% with 240/160 mg, 96.4% with leuprolide. Day 3 castration: 96% versus 0%. Leuprolide patients had a testosterone surge in week 1 (median rise of about 65%) and PSA fell more slowly. Adverse events were similar apart from injection site reactions (about 40% on degarelix versus under 1%) and chills. Later pooled analyses suggested fewer cardiovascular events with antagonists in men with pre-existing cardiovascular disease, a hypothesis that dedicated trials have not confirmed.", "animal_evidence": "Preclinical rodent and primate studies established rapid, reversible testosterone suppression without a flare and characterized the depot pharmacokinetics. No carcinogenicity signal relevant to human dosing was found.", "conditions": [], "literature_dosing": "FDA label (Firmagon, DailyMed; subcutaneous injection in the abdomen by a healthcare professional only): starting dose 240 mg given as two injections of 120 mg, then a maintenance dose of 80 mg as a single injection every 28 days, with the first maintenance dose 28 days after the starting dose. The pivotal trial (Klotz 2008) used the same regimen.", "routes": [ "Subcutaneous injection into the abdomen every 28 days (loading dose given as two injections)" ], "side_effects": [ "Injection site pain, erythema, swelling, or nodules (about 40% of patients, mostly after the loading dose)", "Hot flashes (about 26% in the pivotal trial)", "Weight gain, fatigue, and increased liver transaminases", "Chills and fever in the first days", "Loss of libido and erectile dysfunction", "Bone density loss and fracture risk with prolonged androgen deprivation", "QT prolongation", "Hyperglycemia and increased cardiovascular risk with long term androgen deprivation" ], "interactions": [ "QT prolonging drugs (class IA and III antiarrhythmics, some antipsychotics and antibiotics): additive risk", "Antidiabetic drugs: glucose control may worsen during androgen deprivation", "No CYP450 mediated interactions identified in vitro" ], "contraindications": [ "Hypersensitivity to degarelix", "Women (not indicated; may cause fetal harm)", "Use with caution in congenital long QT syndrome, electrolyte abnormalities, or heart failure" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Firmagon in December 2008 for advanced prostate cancer. No generic is available as of the last verified date. Because an approved product exists, compounding is not permitted beyond patient specific exceptions.", "typical_cost": "Roughly 600 to 900 USD per monthly 80 mg maintenance injection at list price, with the 240 mg loading dose about twice that. Insurance and Medicare Part B cover it for prostate cancer.", "access_path": [ "Prescription from a urologist or oncologist, administered in clinic as a monthly subcutaneous injection.", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is degarelix (Firmagon) FDA approved, and what is it used for?", "a": "Yes. Firmagon has been approved since December 2008, and its label has one use: treatment of patients with advanced prostate cancer. It is prescription only and is given in a clinic as a subcutaneous injection (under the skin) every 28 days.", "source_ids": [ "fda-firmagon-label" ] }, { "q": "How fast does degarelix lower testosterone?", "a": "Within days. In the 610 patient pivotal trial, 96% of men on degarelix reached castrate testosterone by day 3, compared with none on leuprolide, which caused a testosterone surge in the first week before suppression. From day 28 through 1 year, 97 to 98% of degarelix patients stayed castrate versus 96.4% on leuprolide.", "source_ids": [ "klotz-2008" ] }, { "q": "What are the side effects of degarelix?", "a": "Injection site pain, redness, and swelling affect about 40% of patients, mostly after the large loading dose, and chills can occur in the first days. Beyond that the effects are those of low testosterone: hot flashes (about 26%), weight gain, fatigue, loss of libido, erectile dysfunction, bone loss, and higher diabetes and cardiovascular risk with long term use. Liver enzyme elevations and QT prolongation are also on the label.", "source_ids": [ "klotz-2008", "fda-firmagon-label" ] }, { "q": "What is the degarelix (Firmagon) dose on the FDA label?", "a": "A 240 mg starting dose given as two 120 mg injections under the skin of the abdomen, then 80 mg once every 28 days. A healthcare professional gives every dose, in areas of the abdomen away from waistbands and ribs. Because degarelix blocks GnRH receptors directly, it does not cause the testosterone flare seen with GnRH agonists, so no antiandrogen cover is needed.", "source_ids": [ "fda-firmagon-label", "klotz-2008" ] }, { "q": "How much does degarelix cost?", "a": "Roughly 600 to 900 USD per monthly maintenance injection at list price, and about double for the loading dose. Insurance and Medicare Part B cover it for prostate cancer. No generic exists. Prices were checked on the last verified date.", "source_ids": [ "fda-firmagon-label" ] }, { "q": "Is degarelix banned by WADA?", "a": "It is not named on the WADA Prohibited List. Section S2 prohibits GnRH and its analogs in males, and WADA's examples are all agonists; degarelix is an antagonist that lowers testosterone and has no performance rationale. Athletes on it for cancer should still notify their anti-doping organization and consider a therapeutic use exemption.", "source_ids": [ "wada-list" ] }, { "q": "Degarelix vs leuprolide: which is better?", "a": "Both keep about 96 to 98% of men castrate through a year. Degarelix works within 3 days with no flare, so it is preferred when a testosterone surge could cause spinal cord compression or urinary obstruction, and it lowers PSA faster. Leuprolide is cheaper, has 3 to 6 month depots, and causes far fewer injection site reactions (under 1% versus about 40%).", "source_ids": [ "klotz-2008" ] } ], "studies": [ { "pmid": "19035858", "title": "The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer", "year": 2008, "design": "Randomized, open label, active comparator noninferiority trial, 12 months", "n": 610, "population": "Men with histologically confirmed prostate cancer requiring androgen deprivation therapy", "outcome": "Testosterone 0.5 ng/mL or below from day 28 to 364 in 97.2% (240/80 mg) and 98.3% (240/160 mg) versus 96.4% with leuprolide; castration by day 3 in 96% versus 0%; injection site reactions about 40% versus under 1%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19035858/" } ], "sources": [ { "id": "klotz-2008", "type": "pubmed", "title": "Klotz L et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/19035858/", "pmid": "19035858", "year": 2008 }, { "id": "fda-firmagon-label", "type": "fda", "title": "FDA prescribing information for Firmagon (degarelix for injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab11dd8a-0fd9-4013-89ab-e114557c7e4b", "year": 2024 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (GnRH and its analogs in males)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "leuprolide", "triptorelin", "cetrorelix", "ganirelix" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Degarelix (Firmagon): uses, side effects, and dosing", "description": "Firmagon is degarelix, a monthly GnRH antagonist injection for advanced prostate cancer. FDA label use and dose, side effects, degarelix vs leuprolide, cost.", "h1": "Degarelix (Firmagon)" } }, { "slug": "vasopressin", "name": "Vasopressin", "aliases": [ "Arginine vasopressin", "AVP", "Antidiuretic hormone", "ADH", "Vasostrict", "8-arginine vasopressin" ], "class": "Endogenous nonapeptide hormone of the posterior pituitary (V1a, V1b, and V2 receptor agonist)", "one_liner": "Natural pituitary hormone, FDA approved as an ICU drug to raise blood pressure in shock; the 778 patient VASST trial found no survival gain over norepinephrine.", "summary": "Vasopressin is the nine amino acid antidiuretic (water retaining) hormone released by the back of the pituitary gland; as a drug it is an intravenous vasopressor (a blood pressure raising drug) FDA approved in 2014 (Vasostrict) to raise blood pressure in vasodilatory shock, dangerously low blood pressure from widened blood vessels. In the 778 patient VASST trial, adding low dose vasopressin to norepinephrine in septic shock (shock from infection) did not change 28 day mortality (35.4% versus 39.3%), and the 409 patient VANISH trial found no reduction in kidney failure, though fewer patients needed dialysis. It is a hospital only drug with no role outside critical care, and the vasopressin sold online as a nootropic (supposed memory enhancer) or nasal spray has no supporting evidence.", "mechanism": "Vasopressin acts on V1a receptors on vascular smooth muscle to cause vasoconstriction, on V2 receptors in the renal collecting duct to insert aquaporin channels and concentrate urine, and on V1b receptors in the pituitary to release ACTH. In septic shock, endogenous vasopressin is relatively deficient, which is the rationale for low dose replacement. It also acts as a neurotransmitter involved in social behavior in animals, the basis for research interest in intranasal use.", "evidence_grade": "human_rct", "evidence_summary": "Two large randomized trials in septic shock. VASST (n = 778): vasopressin 0.01 to 0.03 units per minute plus norepinephrine versus norepinephrine alone; 28 day mortality 35.4% versus 39.3% (not significant), with a possible benefit in less severe shock. VANISH (n = 409): early vasopressin versus norepinephrine; kidney failure free days did not differ, but fewer vasopressin patients received renal replacement therapy (25.4% versus 35.3%). Both trials support vasopressin as a safe norepinephrine sparing agent rather than a survival improving one. Approval for post cardiotomy and septic shock rests on these and hemodynamic studies.", "human_evidence": "Russell 2008 (VASST): 778 patients with septic shock on at least 5 ug/min norepinephrine randomized to add vasopressin 0.01 to 0.03 units/min or more norepinephrine; 28 day mortality 35.4% versus 39.3% (p = 0.26), 90 day mortality 43.9% versus 49.6% (p = 0.11); in the prespecified less severe shock stratum 28 day mortality was 26.5% versus 35.7%. Gordon 2016 (VANISH): 409 adults with septic shock randomized in a factorial design to vasopressin (up to 0.06 units/min) or norepinephrine, with hydrocortisone or placebo; kidney failure free days did not differ, renal replacement therapy 25.4% versus 35.3%, mortality 30.9% versus 27.5% (not significant). No randomized trial supports intranasal vasopressin for cognition, social behavior, or muscle growth.", "animal_evidence": "Animal work characterized receptor pharmacology and the role of vasopressin in water balance, blood pressure, and stress responses. Rodent and vole studies show vasopressin shapes pair bonding, aggression, and social memory, which prompted small human intranasal studies with mixed results. Sepsis models show relative vasopressin deficiency and improved hemodynamics with replacement.", "conditions": [], "literature_dosing": "FDA label (Vasostrict, DailyMed; continuous intravenous infusion in hospital, diluted to 0.1 or 1 unit/mL unless supplied premixed): post cardiotomy shock, 0.03 to 0.1 units per minute; septic shock, 0.01 to 0.07 units per minute. The label gives no subcutaneous, intranasal, or other outpatient dose.", "routes": [ "Continuous intravenous infusion (ICU)", "Intravenous or intraosseous bolus (resuscitation protocols, off label)", "Intranasal (research only)" ], "side_effects": [ "Peripheral, mesenteric, and coronary ischemia including digital necrosis and bowel ischemia at higher doses", "Bradycardia and arrhythmias", "Hyponatremia and water retention (V2 effect)", "Decreased cardiac output", "Skin necrosis with extravasation", "Reversible thrombocytopenia (VASST reported more with vasopressin)" ], "interactions": [ "Catecholamine vasopressors: additive pressor effect (intended)", "Drugs that cause SIADH (carbamazepine, chlorpropamide, tricyclics, SSRIs): increased antidiuretic effect", "Ganglionic blockers: enhanced pressor response", "Indomethacin: prolongs the effect of vasopressin" ], "contraindications": [ "Hypersensitivity to vasopressin or chlorobutanol (preservative in some vials)", "Use with extreme caution in coronary artery disease, peripheral vascular disease, and chronic nephritis with nitrogen retention", "Not for use outside a monitored setting" ], "wada_status": "unclear", "fda_status": "fda_approved", "compounding_status": "Vasopressin injection was marketed for decades as an unapproved drug and became FDA approved as Vasostrict in April 2014 for vasodilatory shock; generic vasopressin injections were approved beginning in 2021. Hospital pharmacies may prepare diluted infusions from approved vials. Vasopressin sold online for intranasal use as a cognitive or social enhancer is not an approved product and is not compounded by licensed pharmacies for that purpose.", "typical_cost": "Hospital only; a 20 unit vial of generic vasopressin costs roughly 30 to 150 USD to the hospital and is billed as part of ICU care. No outpatient product exists.", "access_path": [ "Administered intravenously in hospitals and intensive care units; not dispensed to patients.", "Products sold online for intranasal use are unapproved and not lawful for human use." ], "faqs": [ { "q": "Is vasopressin (Vasostrict) FDA approved, and what is it used for?", "a": "Yes, as Vasostrict since 2014. The label covers one use: increasing blood pressure in adults with vasodilatory shock, dangerously low blood pressure from widened blood vessels (for example septic or post cardiac surgery shock), who remain hypotensive (low blood pressure) despite fluids and catecholamines, the standard blood pressure drugs such as norepinephrine. Generic vasopressin injections followed. It is given only by intravenous infusion in hospital.", "source_ids": [ "fda-vasostrict-label" ] }, { "q": "Does vasopressin improve survival in septic shock?", "a": "Not clearly. In VASST, 778 patients with septic shock received vasopressin or more norepinephrine; 28 day mortality was 35.4% versus 39.3%, a difference that was not statistically significant, although patients with less severe shock did better on vasopressin. In VANISH, early vasopressin did not reduce kidney failure but fewer patients needed dialysis (25.4% versus 35.3%). Guidelines position it as an add on to reduce norepinephrine dose.", "source_ids": [ "vasst-2008", "vanish-2016" ] }, { "q": "What are the side effects of vasopressin?", "a": "It constricts blood vessels everywhere, so the serious risks are ischemia of fingers, gut, and heart, especially at higher infusion rates, plus slow heart rate, reduced cardiac output, and water retention with low sodium. VASST reported more digital ischemia and a small excess of arrhythmias in a non significant range. Extravasation can cause skin necrosis.", "source_ids": [ "vasst-2008", "fda-vasostrict-label" ] }, { "q": "What is the vasopressin (Vasostrict) dose on the FDA label?", "a": "A continuous intravenous infusion in intensive care: 0.03 to 0.1 units per minute for shock after cardiac surgery and 0.01 to 0.07 units per minute for septic shock, with blood pressure monitored continuously. There is no labeled outpatient, nasal, or injection dose.", "source_ids": [ "fda-vasostrict-label" ] }, { "q": "Does intranasal vasopressin work as a nootropic or for social bonding?", "a": "There is no randomized evidence of benefit. Animal studies link vasopressin to social memory and bonding, and a handful of small human intranasal experiments have produced inconsistent effects on social cognition. Products sold online for this purpose are unapproved, and vasopressin's vasoconstrictor and antidiuretic effects make unsupervised use risky.", "source_ids": [ "vanish-2016", "fda-vasostrict-label" ] }, { "q": "How much does vasopressin cost?", "a": "It is a hospital drug billed as part of critical care; a generic 20 unit vial costs the hospital roughly 30 to 150 USD. Brand pricing rose sharply after the 2014 approval before generics arrived in 2021. There is no legitimate outpatient purchase.", "source_ids": [ "fda-vasostrict-label" ] }, { "q": "Is vasopressin banned by WADA?", "a": "Unclear. Vasopressin itself is not named on the WADA Prohibited List, but its synthetic analog desmopressin is listed under S5 as a masking agent because it dilutes urine. Vasopressin has the same antidiuretic action, so athletes should treat it as high risk and consult their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Vasopressin vs desmopressin: what is the difference?", "a": "Vasopressin is the natural hormone and acts on both blood vessel (V1) and kidney (V2) receptors, so it is used as an ICU vasopressor. Desmopressin is a modified analog that is selective for V2 receptors, lasts longer, and does not raise blood pressure, so it is used as an outpatient drug for diabetes insipidus, bedwetting, nocturia, and bleeding disorders.", "source_ids": [ "fda-vasostrict-label" ] } ], "studies": [ { "pmid": "18305265", "title": "Vasopressin versus norepinephrine infusion in patients with septic shock (VASST)", "year": 2008, "design": "Randomized, double blind, active controlled trial", "n": 778, "population": "Adults with septic shock receiving at least 5 ug/min norepinephrine", "outcome": "28 day mortality 35.4% with vasopressin versus 39.3% with norepinephrine (p = 0.26); 90 day mortality 43.9% versus 49.6%; possible benefit in less severe shock", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18305265/" }, { "pmid": "27483065", "title": "Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial", "year": 2016, "design": "Randomized, double blind, factorial (vasopressin or norepinephrine, hydrocortisone or placebo) trial", "n": 409, "population": "Adults with septic shock within 6 hours of onset", "outcome": "No difference in kidney failure free days; renal replacement therapy 25.4% versus 35.3%; mortality 30.9% versus 27.5% (not significant)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27483065/" } ], "sources": [ { "id": "vasst-2008", "type": "pubmed", "title": "Russell JA et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008 (VASST)", "url": "https://pubmed.ncbi.nlm.nih.gov/18305265/", "pmid": "18305265", "year": 2008 }, { "id": "vanish-2016", "type": "pubmed", "title": "Gordon AC et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27483065/", "pmid": "27483065", "year": 2016 }, { "id": "fda-vasostrict-label", "type": "fda", "title": "FDA prescribing information for Vasostrict (vasopressin injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1147beb-743e-4c62-8927-91192447f8b8", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S5 diuretics and masking agents", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "desmopressin", "terlipressin", "oxytocin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Vasopressin (Vasostrict): uses, side effects, and dosing", "description": "Vasostrict is vasopressin, an IV hospital drug that raises blood pressure in vasodilatory shock. FDA label use and infusion doses, side effects, and cost.", "h1": "Vasopressin (Vasostrict)" } }, { "slug": "desmopressin", "name": "Desmopressin", "aliases": [ "DDAVP", "Desmopressin acetate", "1-deamino-8-D-arginine vasopressin", "Nocdurna", "Noctiva", "Stimate", "Minirin" ], "class": "Synthetic nonapeptide analog of vasopressin, selective for the V2 receptor", "one_liner": "FDA approved since 1978 for central diabetes insipidus, bleeding disorders, bedwetting, and nighttime urination; boxed warning for low blood sodium.", "summary": "Desmopressin is a modified vasopressin (a lab-made version of the body's water-saving hormone) that acts almost only on kidney V2 receptors, so it concentrates urine for 8 to 12 hours without raising blood pressure, and at high doses it releases the stored clotting proteins factor VIII and von Willebrand factor. It has been FDA approved since 1978 for central diabetes insipidus (the brain makes too little of this hormone, causing heavy urination and thirst) and is also approved for mild hemophilia A and von Willebrand disease type 1, primary nocturnal enuresis (bedwetting; tablets), and nocturia due to nocturnal polyuria, waking to urinate because the body makes too much urine at night (Nocdurna, Noctiva). Its main risk is hyponatremia (dangerously low blood sodium), which prompted a 2007 FDA alert and the withdrawal of the nasal spray for bedwetting, and low dose nocturia products carry a boxed warning, FDA's most serious label warning.", "mechanism": "Desmopressin binds V2 receptors on renal collecting duct cells, raising cyclic AMP and moving aquaporin-2 water channels to the cell surface, so water is reabsorbed and urine concentrates. The deamination and D-arginine substitution remove most V1 (vasoconstrictor) activity and extend duration. At doses roughly 10 times higher than antidiuretic doses, V2 stimulation of endothelial cells releases factor VIII and von Willebrand factor, raising plasma levels 3 to 5 fold within an hour.", "evidence_grade": "human_rct", "evidence_summary": "Extensive randomized and controlled evidence across indications. For bleeding disorders, 20 years of studies reviewed by Mannucci 1997 show a 3 to 5 fold rise in factor VIII and von Willebrand factor in responders with mild hemophilia A and type 1 von Willebrand disease. For nocturia, a 2014 systematic review found desmopressin reduced nocturnal voids by roughly half a void per night more than placebo and prolonged the first undisturbed sleep period, with hyponatremia as the limiting harm. Weatherall 2004 pooled older adult studies and found clinically significant hyponatremia in about 7.6% of those treated for nocturia. Enuresis and diabetes insipidus efficacy rest on the original label trials.", "human_evidence": "Mannucci 1997: review of two decades of clinical use showing desmopressin 0.3 ug/kg raises factor VIII and von Willebrand factor about 3 to 5 fold in mild hemophilia A and type 1 von Willebrand disease, allowing many minor procedures without plasma products. Ebell 2014: systematic review of randomized trials of desmopressin for adult nocturia; desmopressin reduced nocturnal voids modestly versus placebo (on the order of 0.5 to 1 fewer voids per night) and increased the time to first void, with hyponatremia more frequent in older patients and at higher doses. Weatherall 2004: meta-analysis of desmopressin for nocturia in older adults, pooled incidence of hyponatremia 7.6%. Juul 2017: low doses (25 ug women, 50 ug men) with serum sodium monitoring reduced clinically significant hyponatremia, the basis of the sex specific dosing in Nocdurna.", "animal_evidence": "Animal pharmacology established V2 selectivity, minimal pressor effect, and the antidiuretic dose response; toxicology found no carcinogenicity signal. Human data supersede animal work for this drug.", "conditions": [ "sleep" ], "literature_dosing": "FDA labels (DailyMed). DDAVP tablets: central diabetes insipidus, start at 0.05 mg twice daily and adjust; most patients use 0.1 to 0.8 mg a day in divided doses, within a 0.1 to 1.2 mg daily range; primary nocturnal enuresis (age 6 and older), 0.2 mg at bedtime, titrated up to 0.6 mg, with fluids limited from 1 hour before the dose until the next morning. Desmopressin nasal spray, central diabetes insipidus: 10 to 40 mcg a day in adults as one dose or divided into two or three, and 10 up to 30 mcg a day in children 4 and older; it is not indicated for bedwetting. DDAVP injection: diabetes insipidus, 2 to 4 mcg a day subcutaneously or intravenously in one or two doses; hemophilia A and type 1 von Willebrand disease with factor VIII above 5%, 0.3 mcg/kg (maximum 20 mcg) by intravenous infusion. Serum sodium is checked because every form can cause hyponatremia.", "routes": [ "Oral tablet", "Sublingual tablet (Nocdurna)", "Intranasal spray (DDAVP nasal, Stimate, Noctiva)", "Intravenous or subcutaneous injection" ], "side_effects": [ "Hyponatremia, which can cause headache, nausea, confusion, seizures, and death; highest risk in older adults, at higher doses, with excess fluid intake, and with the intranasal route (boxed warning on nocturia products)", "Headache, nausea, and flushing", "Nasal congestion and rhinitis with intranasal use", "Transient blood pressure changes and tachycardia with intravenous dosing", "Tachyphylaxis with repeated hemostatic doses over several days", "Rare thrombotic events at hemostatic doses in patients with cardiovascular disease" ], "interactions": [ "Loop diuretics and systemic or inhaled glucocorticoids: contraindicated with nocturia products due to hyponatremia risk", "Tricyclic antidepressants, SSRIs, carbamazepine, chlorpromazine, NSAIDs, opioids, and lamotrigine: increase antidiuretic effect and hyponatremia risk", "Lithium and demeclocycline: decrease antidiuretic response", "Excess fluid intake around dosing increases hyponatremia risk" ], "contraindications": [ "Hyponatremia or a history of hyponatremia", "Moderate to severe renal impairment (creatinine clearance below 50 mL/min)", "Syndrome of inappropriate antidiuretic hormone secretion", "Polydipsia, heart failure, or uncontrolled hypertension (nocturia products)", "Illnesses causing fluid or electrolyte imbalance (fever, vomiting, diarrhea) while taking it", "Type 2B von Willebrand disease (desmopressin causes platelet aggregation) and hemophilia A with factor VIII under 5%" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as DDAVP injection in 1978 for central diabetes insipidus, with nasal and tablet forms following for diabetes insipidus, hemophilia A, von Willebrand disease type 1, and primary nocturnal enuresis. In December 2007 FDA alerted prescribers to severe hyponatremia and removed the enuresis indication from intranasal products. Noctiva (2017) and Nocdurna (2018) were approved for nocturia due to nocturnal polyuria with a boxed warning for hyponatremia. Generic tablets, nasal sprays, and injections are widely available, so compounding is limited to patient specific needs.", "typical_cost": "Generic desmopressin tablets cost roughly 20 to 80 USD per month at cash prices; generic nasal spray roughly 50 to 200 USD per bottle. Nocdurna and Noctiva brand products list at several hundred USD per month. Insurance generally covers desmopressin for approved indications.", "access_path": [ "Prescription from a primary care provider, urologist, hematologist, endocrinologist, or pediatrician, filled at any retail pharmacy.", "Hospital administration for hemostatic dosing before procedures.", "Not available through telehealth peptide clinics; not compounded because generics exist." ], "faqs": [ { "q": "Is desmopressin FDA approved, and what is it used for?", "a": "Yes, since 1978. Current DDAVP labels cover central diabetes insipidus (too little of the body's water-saving hormone, causing heavy urination and thirst; tablets, nasal spray, and injection), primary nocturnal enuresis (bedwetting; tablets only), and, for the injection, maintaining hemostasis (stopping bleeding) in hemophilia A and type 1 von Willebrand disease when factor VIII activity is above 5%. Low dose products for nocturia due to nocturnal polyuria (waking to urinate because of excess nighttime urine; Nocdurna and Noctiva) were also approved. It is prescription only and available as generics.", "source_ids": [ "fda-ddavp-label", "fda-ddavp-injection-label", "fda-desmopressin-nasal-label", "fda-nocdurna-label" ] }, { "q": "Does desmopressin work for nocturia?", "a": "Modestly. A 2014 systematic review of randomized trials found desmopressin cut nighttime urination by roughly half a void to one void per night more than placebo and lengthened the first stretch of undisturbed sleep. The trade off is hyponatremia, which occurred in about 7.6% of older adults in pooled studies, so the approved nocturia products use low sex specific doses and require sodium checks.", "source_ids": [ "ebell-2014", "weatherall-2004", "juul-2017" ] }, { "q": "How does desmopressin stop bleeding in hemophilia and von Willebrand disease?", "a": "At about 10 times the antidiuretic dose (0.3 ug/kg intravenously or 300 ug intranasally), desmopressin releases stored factor VIII and von Willebrand factor from blood vessel walls, raising levels 3 to 5 fold within an hour in responders. It works in mild hemophilia A and type 1 von Willebrand disease, not in severe hemophilia, and the response fades with repeated daily doses.", "source_ids": [ "mannucci-1997" ] }, { "q": "What are the side effects of desmopressin?", "a": "The serious one is low sodium (hyponatremia), which can cause headache, confusion, seizures, and death, and is most likely in older adults, at higher doses, with excess drinking, and with nasal sprays. FDA issued an alert in 2007 after seizures in children using the nasal spray for bedwetting, and the nocturia products carry a boxed warning. Common milder effects are headache, nausea, flushing, and nasal irritation.", "source_ids": [ "fda-ddavp-label", "fda-nocdurna-label", "weatherall-2004" ] }, { "q": "What is the desmopressin (DDAVP) dose on the FDA label?", "a": "It depends on the form and use. Tablets for diabetes insipidus start at 0.05 mg twice daily, with most patients on 0.1 to 0.8 mg a day; tablets for bedwetting are 0.2 mg at bedtime, up to 0.6 mg. The nasal spray for diabetes insipidus is 10 to 40 mcg a day in adults. The injection is 2 to 4 mcg a day for diabetes insipidus, or 0.3 mcg/kg (maximum 20 mcg) by intravenous infusion for hemophilia A and type 1 von Willebrand disease. Fluid restriction and sodium checks go with every form.", "source_ids": [ "fda-ddavp-label", "fda-ddavp-injection-label", "fda-desmopressin-nasal-label" ] }, { "q": "How much does desmopressin cost?", "a": "Generic tablets run roughly 20 to 80 USD per month cash and generic nasal spray 50 to 200 USD per bottle; the branded low dose nocturia products list at several hundred USD per month. Most insurance covers desmopressin for approved indications. Prices were checked on the last verified date.", "source_ids": [ "fda-ddavp-label" ] }, { "q": "Is desmopressin banned by WADA?", "a": "Yes. Desmopressin is listed by name under section S5 (diuretics and masking agents) of the WADA Prohibited List because it dilutes urine and can lower the concentration of other substances. It is prohibited at all times, in and out of competition, and athletes who need it must obtain a therapeutic use exemption.", "source_ids": [ "wada-list" ] }, { "q": "Desmopressin vs vasopressin: what is the difference?", "a": "Desmopressin is vasopressin with two chemical changes that make it selective for kidney V2 receptors, longer lasting, and free of the blood pressure raising V1 effect, so it can be taken at home by mouth or nose. Vasopressin acts on both receptor types and is used only as an intravenous vasopressor in intensive care.", "source_ids": [ "fda-ddavp-label" ] } ], "studies": [ { "pmid": "9326215", "title": "Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years", "year": 1997, "design": "Narrative review of clinical studies", "population": "Patients with mild hemophilia A, type 1 von Willebrand disease, and platelet function disorders", "outcome": "Desmopressin 0.3 ug/kg raises factor VIII and von Willebrand factor 3 to 5 fold in responders and allows minor surgery without plasma products; tachyphylaxis with repeated dosing", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9326215/" }, { "pmid": "24704009", "title": "A systematic review of the efficacy and safety of desmopressin for nocturia in adults", "year": 2014, "design": "Systematic review of randomized controlled trials", "population": "Adults with nocturia", "outcome": "Modest reduction in nocturnal voids and longer first undisturbed sleep period versus placebo; hyponatremia more common with age and dose", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/24704009/" }, { "pmid": "15227644", "title": "The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis", "year": 2004, "design": "Systematic review and meta-analysis", "population": "Older adults treated with desmopressin for nocturia", "outcome": "Pooled incidence of hyponatremia about 7.6%, supporting sodium monitoring and dose limits in older patients", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/15227644/" }, { "pmid": "27862898", "title": "Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia", "year": 2017, "design": "Pooled analysis of randomized trials of low dose desmopressin", "population": "Adults with nocturia treated with 25 ug (women) or 50 ug (men) orally disintegrating desmopressin", "outcome": "Sex specific low doses with serum sodium monitoring markedly reduced clinically significant hyponatremia", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27862898/" } ], "sources": [ { "id": "mannucci-1997", "type": "pubmed", "title": "Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 1997", "url": "https://pubmed.ncbi.nlm.nih.gov/9326215/", "pmid": "9326215", "year": 1997 }, { "id": "ebell-2014", "type": "pubmed", "title": "Ebell MH et al. A systematic review of the efficacy and safety of desmopressin for nocturia in adults. J Urol 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24704009/", "pmid": "24704009", "year": 2014 }, { "id": "weatherall-2004", "type": "pubmed", "title": "Weatherall M. The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis. Neurourol Urodyn 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15227644/", "pmid": "15227644", "year": 2004 }, { "id": "juul-2017", "type": "pubmed", "title": "Juul KV et al. Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia. BJU Int 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/27862898/", "pmid": "27862898", "year": 2017 }, { "id": "fda-ddavp-label", "type": "fda", "title": "FDA prescribing information for DDAVP (desmopressin acetate) tablets, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6d55baa9-2b62-469c-93ae-3909ab249332", "year": 2025 }, { "id": "fda-nocdurna-label", "type": "fda", "title": "FDA prescribing information for Nocdurna (desmopressin acetate) sublingual tablets, with boxed warning for hyponatremia, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=nocdurna", "year": 2024 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S5 diuretics and masking agents (desmopressin)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-ddavp-injection-label", "type": "fda", "title": "FDA prescribing information for DDAVP (desmopressin acetate) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=651f6fee-a2c7-431b-8d5d-58b156c72244", "year": 2022 }, { "id": "fda-desmopressin-nasal-label", "type": "fda", "title": "FDA prescribing information for desmopressin acetate nasal spray, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1ac423b8-27a6-4cef-4a82-c50bf81b4f49", "year": 2026 } ], "related": [ "vasopressin", "terlipressin", "oxytocin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Desmopressin (DDAVP): uses, side effects, and dosing", "description": "DDAVP is desmopressin, a vasopressin analog for diabetes insipidus, bedwetting, hemophilia A, and von Willebrand disease. Label uses, doses, low sodium risk.", "h1": "Desmopressin (DDAVP)" } }, { "slug": "calcitonin", "name": "Calcitonin", "aliases": [ "Calcitonin-salmon", "Salmon calcitonin", "Miacalcin", "Fortical", "Calcimar", "sCT" ], "class": "32 amino acid thyroid C cell hormone; the drug is synthetic salmon calcitonin, which is more potent and longer acting than the human form", "one_liner": "FDA approved salmon calcitonin for Paget disease, high blood calcium, and osteoporosis; weak fracture data and a 2013 cancer signal restricted its use.", "summary": "Calcitonin is a 32 amino acid hormone that lowers blood calcium by slowing osteoclasts, the cells that break down bone; the drug form is synthetic salmon calcitonin, FDA approved as an injection since 1975 for Paget disease (a disorder of abnormal, weakened bone growth) and hypercalcemia (high blood calcium) and as a nasal spray since 1995 for postmenopausal osteoporosis. Its osteoporosis evidence is weak: the 5 year PROOF trial found a 33% reduction in new vertebral (spine) fractures only at the 200 IU dose, with no dose response (the effect did not rise with dose) and 59% dropout. In 2013 an FDA meta-analysis (a pooled analysis) of 21 trials found malignancy (cancer) in 4.1% of calcitonin treated patients versus 2.9% on placebo, and FDA restricted the osteoporosis indication to women more than 5 years past menopause for whom alternatives are not suitable.", "mechanism": "Calcitonin binds the calcitonin receptor on osteoclasts and rapidly inhibits bone resorption, lowering serum calcium; it also increases renal calcium excretion. The effect on osteoclasts wanes with continuous exposure (escape phenomenon), which limits its potency compared with bisphosphonates. Salmon calcitonin is about 40 to 50 times more potent than human calcitonin at the receptor. Calcitonin also has a central analgesic effect that is exploited for painful vertebral fractures.", "evidence_grade": "human_rct", "evidence_summary": "PROOF (n = 1,255) is the pivotal osteoporosis trial: 5 years of nasal calcitonin 100, 200, or 400 IU daily versus placebo. Only the 200 IU dose reduced new vertebral fractures (relative risk 0.67, 33% reduction); the 100 and 400 IU doses did not, there was no dose response, bone density gains were about 1 to 1.5%, and 59% of participants dropped out, all of which weaken the result. Hip and nonvertebral fractures were not reduced. Efficacy in Paget disease and hypercalcemia is documented in older controlled studies summarized in the label. A 2016 meta-analysis reviewed the malignancy signal that FDA had identified in 2013 and found the association weak and inconsistent across studies.", "human_evidence": "Chesnut 2000 (PROOF): 1,255 postmenopausal women with established osteoporosis randomized to nasal salmon calcitonin 100, 200, or 400 IU daily or placebo for 5 years; new vertebral fractures 200 IU versus placebo relative risk 0.67 (95% CI 0.47 to 0.97); no significant reduction at 100 or 400 IU; lumbar spine BMD rose 1 to 1.5%; 59% withdrew. FDA 2013: meta-analysis of 21 randomized trials found malignancies in 4.1% of calcitonin treated versus 2.9% of placebo treated patients, driven heavily by one 5 year trial; FDA concluded causality could not be established but restricted the osteoporosis indication. Wells 2016: independent meta-analysis found the cancer association was not consistent across trials.", "animal_evidence": "Salmon calcitonin was characterized in rat and rabbit models of hypercalcemia and bone resorption in the 1960s and 1970s. Animal carcinogenicity studies did not predict the malignancy signal later seen in human trial meta-analyses, and no mechanism for it has been established.", "conditions": [], "literature_dosing": "FDA labels (DailyMed). Miacalcin injection, by subcutaneous or intramuscular injection: symptomatic Paget disease of bone, 100 USP units daily; hypercalcemia, 4 USP units/kg every 12 hours, increased to 8 units/kg every 12 hours if the response is unsatisfactory after 1 to 2 days, and to a maximum of 8 units/kg every 6 hours after 2 more days; postmenopausal osteoporosis in women more than 5 years past menopause, 100 USP units daily. Calcitonin salmon nasal spray, postmenopausal osteoporosis: one spray (200 USP units) daily, alternating nostrils, with at least 1,000 mg of elemental calcium and 400 IU of vitamin D a day.", "routes": [ "Intranasal spray once daily (osteoporosis)", "Subcutaneous or intramuscular injection (Paget disease, hypercalcemia, osteoporosis)" ], "side_effects": [ "Rhinitis, nasal dryness, crusting, and epistaxis with nasal spray (rhinitis in about 12% versus 7% placebo in PROOF)", "Nausea, flushing, and injection site reactions with injection", "Hypocalcemia with tetany (rare, mainly with injection)", "Hypersensitivity reactions including anaphylaxis (skin testing is suggested before injection in suspected sensitivity)", "Malignancy: 4.1% versus 2.9% in FDA's 2013 meta-analysis of 21 trials, causality not established", "Antibody formation with long term use, associated with loss of effect" ], "interactions": [ "Lithium: calcitonin may lower lithium levels by increasing renal excretion", "Bisphosphonates: additive calcium lowering; no added fracture benefit shown", "Calcium and vitamin D: required to prevent secondary hyperparathyroidism during osteoporosis treatment" ], "contraindications": [ "Hypersensitivity to salmon calcitonin", "Hypocalcemia", "Osteoporosis in women within 5 years of menopause or in patients for whom other osteoporosis therapies are suitable (per the 2013 label restriction)", "Pregnancy and breastfeeding (not recommended; calcitonin suppresses lactation in animals)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved as Calcimar and later Miacalcin injection in 1975 for Paget disease and hypercalcemia, with postmenopausal osteoporosis added, and as Miacalcin nasal spray in 1995 for osteoporosis; Fortical nasal spray (2005) and generic calcitonin-salmon nasal sprays followed. In March 2013 an FDA advisory committee reviewed the malignancy meta-analysis and the labels were revised to restrict osteoporosis use to women more than 5 years postmenopause for whom alternatives are not suitable and to require periodic reassessment. The European Medicines Agency withdrew nasal calcitonin for osteoporosis in 2012. Compounding is limited to patient specific needs because approved products exist.", "typical_cost": "Generic calcitonin-salmon nasal spray costs roughly 50 to 200 USD per month at cash prices; brand Miacalcin nasal spray lists higher. Injection vials cost roughly 100 to 300 USD each. Insurance coverage for osteoporosis is limited given the restricted indication.", "access_path": [ "Prescription from a primary care provider, endocrinologist, or rheumatologist filled at a retail pharmacy (nasal spray) or given in clinic or hospital (injection).", "Not available through compounding or telehealth peptide clinics." ], "faqs": [ { "q": "Is calcitonin FDA approved, and what is it used for?", "a": "Yes. The Miacalcin injection label covers symptomatic Paget disease of bone (a disorder that makes bone grow abnormally and weaken) when alternative treatments are not suitable, hypercalcemia (high blood calcium), and postmenopausal osteoporosis when alternative treatments are not suitable. The nasal spray is labeled only for postmenopausal osteoporosis in women more than 5 years past menopause when alternatives are not suitable. Both labels state that fracture reduction has not been demonstrated and that the need for continued therapy should be reassessed periodically because of a possible association with malignancy (cancer).", "source_ids": [ "fda-miacalcin-label", "fda-calcitonin-nasal-label" ] }, { "q": "Does calcitonin prevent fractures?", "a": "Weakly. In the 5 year PROOF trial of 1,255 women, only the 200 IU nasal dose reduced new vertebral fractures (33% relative reduction), while 100 and 400 IU did not, there was no dose response, and 59% of participants dropped out. Hip and other nonvertebral fractures were not reduced. Bisphosphonates, denosumab, and anabolic agents have far stronger fracture data, which is why guidelines place calcitonin last.", "source_ids": [ "proof-2000" ] }, { "q": "Does calcitonin cause cancer?", "a": "Possibly, and the question is unresolved. FDA's 2013 meta-analysis of 21 randomized trials found malignancies in 4.1% of calcitonin treated patients versus 2.9% on placebo, heavily influenced by one 5 year trial, and FDA said a causal link could not be established but restricted the osteoporosis indication anyway. A 2016 independent meta-analysis found the association inconsistent across trials. Europe withdrew nasal calcitonin for osteoporosis in 2012 on the same data.", "source_ids": [ "fda-miacalcin-qa", "wells-2016" ] }, { "q": "What are the side effects of calcitonin?", "a": "The nasal spray mainly causes nasal irritation, dryness, crusting, and nosebleeds (rhinitis in about 12% versus 7% on placebo in PROOF). Injections cause nausea, flushing, and injection site reactions. Rare effects include low calcium with tetany and allergic reactions including anaphylaxis. The malignancy signal from the 2013 FDA review is the main long term concern.", "source_ids": [ "proof-2000", "fda-miacalcin-label", "fda-miacalcin-qa" ] }, { "q": "What is the calcitonin dose on the FDA label?", "a": "Nasal spray: one 200 unit spray a day, alternating nostrils, for postmenopausal osteoporosis. Injection: 100 units a day under the skin or into muscle for Paget disease or postmenopausal osteoporosis; for hypercalcemia, 4 units/kg every 12 hours, which can be raised to 8 units/kg every 12 hours and then to a maximum of 8 units/kg every 6 hours. Osteoporosis use is paired with calcium and vitamin D.", "source_ids": [ "fda-miacalcin-label", "fda-calcitonin-nasal-label" ] }, { "q": "How much does calcitonin cost?", "a": "Generic nasal spray costs roughly 50 to 200 USD per month cash, brand more, and injection vials roughly 100 to 300 USD each. Insurance often declines coverage for osteoporosis because of the restricted indication. Prices were checked on the last verified date.", "source_ids": [ "fda-miacalcin-label" ] }, { "q": "Is calcitonin banned by WADA?", "a": "No. Calcitonin is not on the WADA Prohibited List and has no performance enhancing rationale. Athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Calcitonin vs teriparatide for osteoporosis: which is better?", "a": "Teriparatide, by a wide margin. Teriparatide cut new vertebral fractures by 65% and nonvertebral fractures by 53% in its pivotal trial and builds bone; calcitonin reduced vertebral fractures by 33% at one dose only, with no nonvertebral benefit and a possible cancer signal. Calcitonin's remaining niches are short term pain relief after acute vertebral fractures and patients who cannot use other agents.", "source_ids": [ "proof-2000", "fda-miacalcin-qa" ] } ], "studies": [ { "pmid": "10996576", "title": "A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study (PROOF)", "year": 2000, "design": "Randomized, double blind, placebo controlled trial, 5 years", "n": 1255, "population": "Postmenopausal women with established osteoporosis and prior vertebral fractures", "outcome": "New vertebral fractures reduced 33% with 200 IU daily (relative risk 0.67); no significant effect at 100 or 400 IU; no reduction in nonvertebral fractures; 59% dropout", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/10996576/" }, { "pmid": "26438308", "title": "Does salmon calcitonin cause cancer? A review and meta-analysis", "year": 2016, "design": "Systematic review and meta-analysis of randomized trials", "population": "Participants in randomized trials of salmon calcitonin", "outcome": "Association between calcitonin and malignancy was inconsistent across trials and not established as causal", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26438308/" } ], "sources": [ { "id": "proof-2000", "type": "pubmed", "title": "Chesnut CH 3rd et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study (PROOF). Am J Med 2000", "url": "https://pubmed.ncbi.nlm.nih.gov/10996576/", "pmid": "10996576", "year": 2000 }, { "id": "wells-2016", "type": "pubmed", "title": "Wells G et al. Does salmon calcitonin cause cancer? A review and meta-analysis. Osteoporos Int 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26438308/", "pmid": "26438308", "year": 2016 }, { "id": "fda-miacalcin-qa", "type": "fda", "title": "FDA: Questions and answers, changes to the indicated population for Miacalcin (calcitonin-salmon), 2013 malignancy meta-analysis (Wayback Machine capture of the FDA page, July 16, 2019)", "url": "https://web.archive.org/web/20190716120513/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-changes-indicated-population-miacalcin-calcitonin-salmon", "year": 2013 }, { "id": "fda-miacalcin-label", "type": "fda", "title": "FDA prescribing information for Miacalcin (calcitonin salmon) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26caf31f-7f7c-48a8-a1ac-35d2ceefda2b", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-calcitonin-nasal-label", "type": "fda", "title": "FDA prescribing information for calcitonin salmon nasal spray, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c82eb602-12e1-692b-d660-f8d5b5736b54", "year": 2026 } ], "related": [ "teriparatide", "abaloparatide" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Calcitonin (Miacalcin): uses, side effects, and dosing", "description": "Miacalcin is calcitonin salmon, an injection and nasal spray for Paget disease, hypercalcemia, and osteoporosis. Label uses, doses, side effects, cancer risk.", "h1": "Calcitonin salmon (Miacalcin)" } }, { "slug": "linaclotide", "name": "Linaclotide", "aliases": [ "Linzess", "Constella", "MD-1100", "MM-416775" ], "class": "Guanylate cyclase-C agonist (synthetic 14 amino acid peptide related to bacterial heat stable enterotoxin)", "one_liner": "FDA approved capsule for irritable bowel syndrome with constipation (IBS-C) and chronic constipation; about 34% respond versus 14% to 21% on placebo.", "summary": "Linaclotide is an FDA approved once daily oral peptide (Linzess, approved August 2012) for irritable bowel syndrome with constipation (IBS-C) in adults and children 7 and older, chronic idiopathic constipation (long term constipation with no known cause) in adults, and functional constipation in children 2 and older. In two phase 3 trials of about 800 IBS-C patients each, 33.6% to 33.7% met the combined responder endpoint, meaning less abdominal pain plus more complete bowel movements, versus 13.9% to 21.0% on placebo (a dummy capsule), and diarrhea was the main side effect. It is a prescription drug sold at retail pharmacies, not a compounded or research peptide.", "mechanism": "Linaclotide binds guanylate cyclase-C on the luminal surface of intestinal epithelial cells. This raises intracellular cyclic GMP, which activates the CFTR ion channel, increasing chloride and bicarbonate secretion into the gut and accelerating transit. Extracellular cyclic GMP is also thought to reduce the firing of visceral pain afferents. The peptide is minimally absorbed and acts locally in the gut.", "evidence_grade": "human_rct", "evidence_summary": "Four large phase 3 randomized placebo controlled trials support approval. In IBS-C, a 26 week trial (n = 804) and a 12 week trial (n = 800) both showed about 34% combined responders versus 14% to 21% on placebo. In chronic constipation, two 12 week trials (n = 1,276 combined) showed complete spontaneous bowel movement responder rates of 16% to 21% versus 3% to 6% on placebo. Diarrhea occurred in about 20% of treated patients.", "human_evidence": "Chey 2012 (26 weeks, n = 804): 290 mcg daily produced a combined abdominal pain and complete spontaneous bowel movement responder rate of 33.7% versus 13.9% with placebo. Rao 2012 (12 weeks plus randomized withdrawal, n = 800): 33.6% versus 21.0% responders, with no rebound worsening after withdrawal. Lembo 2011 (two 12 week trials, n = 630 and 642): complete spontaneous bowel movement responder rates of 21.2% and 16.0% on 145 mcg versus 3.3% and 6.0% on placebo. Diarrhea was the most common adverse event, roughly 20% versus 3% to 5%.", "animal_evidence": "Rodent studies established the guanylate cyclase-C mechanism, increased intestinal fluid secretion and transit, and reduced visceral hypersensitivity. Juvenile mice died from dehydration at doses that were tolerated by adult animals, which is the basis of the pediatric age restriction on the label.", "conditions": [], "literature_dosing": "FDA label (Linzess, DailyMed): adults with IBS-C, 290 mcg orally once daily; adults with chronic idiopathic constipation, 145 mcg once daily, or 72 mcg based on individual presentation or tolerability; children 7 and older with IBS-C, 145 mcg once daily; children 2 and older with functional constipation, 72 mcg once daily. It is taken on an empty stomach at least 30 minutes before a meal at about the same time each day, and the capsule is not crushed or chewed. It is contraindicated under 2 years of age because of a boxed warning for serious dehydration. The phase 3 IBS-C trials used 290 mcg daily.", "routes": [ "Oral capsule once daily" ], "side_effects": [ "Diarrhea (about 20% in IBS-C trials versus 3% to 5% on placebo; severe diarrhea in about 2%)", "Abdominal pain, flatulence, and abdominal distension", "Dehydration from diarrhea, more likely in children and older adults", "Rare reports of fecal incontinence and orthostatic dizziness" ], "interactions": [ "No clinically relevant drug interactions identified; linaclotide is minimally absorbed and does not use cytochrome P450 enzymes", "Additive loose stools with other laxatives or prokinetics (not formally studied)" ], "contraindications": [ "Children under 2 years of age (risk of serious dehydration; deaths in juvenile mice)", "Known or suspected mechanical gastrointestinal obstruction" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Linzess, approved August 30, 2012 for IBS-C and chronic idiopathic constipation; pediatric functional constipation indication added in 2023). It is commercially available, so it is not eligible for routine compounding and is not on any 503A bulks list. Not a research chemical.", "typical_cost": "List price roughly 500 to 600 USD per month for brand Linzess; most insured patients pay a copay and a manufacturer savings card is offered for commercially insured patients. Prices verified on the last verified date and change often.", "access_path": [ "Prescription from a licensed provider (in person or telehealth) filled at a retail pharmacy as Linzess.", "Not available through compounding pharmacies or as a research chemical." ], "faqs": [ { "q": "Is linaclotide (Linzess) FDA approved, and what is it used for?", "a": "Yes. Linzess has been FDA approved since August 2012. The current label covers irritable bowel syndrome with constipation (IBS-C, recurring belly pain with constipation) in adults and children 7 and older, chronic idiopathic constipation (long term constipation with no known cause) in adults, and functional constipation (constipation without an underlying disease) in children 2 and older. It carries a boxed warning, FDA's most serious label warning, against use under age 2 because of serious dehydration. It is a standard prescription drug dispensed at retail pharmacies.", "source_ids": [ "fda-linzess-label" ] }, { "q": "Does linaclotide work for IBS with constipation?", "a": "Yes, in two large randomized trials. Over 26 weeks (n = 804), 33.7% of patients on 290 mcg daily met the combined abdominal pain and bowel movement responder endpoint versus 13.9% on placebo. In a 12 week trial (n = 800), 33.6% responded versus 21.0%. Roughly one in five to one in seven patients benefits beyond placebo, so it helps a meaningful minority rather than everyone.", "source_ids": [ "chey-2012", "rao-2012" ] }, { "q": "Does linaclotide work for chronic constipation?", "a": "Yes. In two 12 week trials of 1,276 adults with chronic constipation, 16.0% to 21.2% of patients on 145 mcg daily had three or more complete spontaneous bowel movements per week with an increase of at least one from baseline, versus 3.3% to 6.0% on placebo. Bowel frequency improved within the first week.", "source_ids": [ "lembo-2011" ] }, { "q": "What are the side effects of linaclotide?", "a": "Diarrhea is the main one, affecting about 20% of IBS-C patients in trials versus 3% to 5% on placebo; in the 26 week trial, 4.5% of patients on linaclotide stopped because of it versus 0.2% on placebo. Abdominal pain, gas, and bloating are also reported. Because of dehydration deaths in juvenile mice, the drug is contraindicated in children under 2.", "source_ids": [ "chey-2012", "fda-linzess-label" ] }, { "q": "What is the linaclotide (Linzess) dose on the FDA label?", "a": "One capsule by mouth once daily on an empty stomach, at least 30 minutes before a meal. Adults take 290 mcg for IBS-C and 145 mcg (or 72 mcg) for chronic idiopathic constipation; children 7 and older with IBS-C take 145 mcg, and children 2 and older with functional constipation take 72 mcg. Diarrhea is the most common side effect.", "source_ids": [ "fda-linzess-label" ] }, { "q": "How much does linaclotide cost?", "a": "The list price of brand Linzess is roughly 500 to 600 USD per month. Most patients with commercial insurance or Medicare Part D pay a copay, and the manufacturer offers a savings card for commercially insured patients. There is no generic in the United States as of the last verified date.", "source_ids": [ "fda-linzess-label" ] }, { "q": "Is linaclotide banned by WADA?", "a": "No. Linaclotide is not on the WADA Prohibited List. It acts locally in the gut and has no performance enhancing effect.", "source_ids": [ "wada-list" ] }, { "q": "Linaclotide vs plecanatide: what is the difference?", "a": "Both are guanylate cyclase-C agonists with the same mechanism and similar responder rates in IBS-C and chronic constipation trials, and both list diarrhea as the main side effect. Linaclotide was approved first (2012) and has more published trial data, including the 26 week Chey trial. There is no head to head randomized trial, so no evidence based ranking exists.", "source_ids": [ "chey-2012", "fda-linzess-label" ] } ], "studies": [ { "pmid": "22986437", "title": "Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety", "year": 2012, "design": "Randomized, double blind, placebo controlled phase 3 trial, 26 weeks", "n": 804, "population": "Adults with IBS-C (Rome II criteria)", "outcome": "Combined abdominal pain and complete spontaneous bowel movement responder rate 33.7% with 290 mcg versus 13.9% with placebo; diarrhea about 20% versus 3%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22986437/" }, { "pmid": "22986440", "title": "A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation", "year": 2012, "design": "Randomized, double blind, placebo controlled phase 3 trial, 12 weeks plus 4 week randomized withdrawal", "n": 800, "population": "Adults with IBS-C", "outcome": "Combined responder rate 33.6% with 290 mcg versus 21.0% with placebo; no rebound after withdrawal", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22986440/" }, { "pmid": "21830967", "title": "Two randomized trials of linaclotide for chronic constipation", "year": 2011, "design": "Two randomized, double blind, placebo controlled phase 3 trials, 12 weeks", "n": 1276, "population": "Adults with chronic constipation", "outcome": "Complete spontaneous bowel movement responder rates 21.2% and 16.0% with 145 mcg versus 3.3% and 6.0% with placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/21830967/" } ], "sources": [ { "id": "chey-2012", "type": "pubmed", "title": "Chey WD et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22986437/", "pmid": "22986437", "year": 2012 }, { "id": "rao-2012", "type": "pubmed", "title": "Rao S et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period of linaclotide in IBS-C. Am J Gastroenterol 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22986440/", "pmid": "22986440", "year": 2012 }, { "id": "lembo-2011", "type": "pubmed", "title": "Lembo AJ et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21830967/", "pmid": "21830967", "year": 2011 }, { "id": "fda-linzess-label", "type": "fda", "title": "FDA prescribing information for Linzess (linaclotide) capsules, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "octreotide", "lanreotide", "vip" ], "cluster": "other", "last_verified": "2026-09-27", "review_status": "draft", "version": 3, "seo": { "title": "Linaclotide (Linzess): uses, side effects, and dosing", "description": "Linzess is linaclotide, a once-daily capsule for IBS with constipation and chronic constipation. FDA label uses and doses, diarrhea risk, and cost.", "h1": "Linaclotide (Linzess)" } }, { "slug": "ziconotide", "name": "Ziconotide", "aliases": [ "Prialt", "SNX-111", "omega-conotoxin MVIIA", "ziconotide intrathecal" ], "class": "Synthetic omega-conotoxin (25 amino acid peptide from the cone snail Conus magus), N-type calcium channel blocker", "one_liner": "FDA approved non-opioid painkiller infused into spinal fluid for severe chronic pain; works for a minority; boxed warning for psychiatric effects.", "summary": "Ziconotide is an FDA approved synthetic cone snail peptide (Prialt, approved December 2004) given by continuous intrathecal infusion, a slow drip into the spinal fluid, through an implanted pump for severe chronic pain that has failed other treatments. In randomized trials, pain scores fell by about 15% to 53% more than placebo depending on how fast the dose was raised, and the drug carries a boxed warning, FDA's most serious label warning, for severe psychiatric symptoms and neurological impairment. It is available only through hospitals and pain clinics that manage intrathecal pumps, never as an injectable or oral product.", "mechanism": "Ziconotide blocks N-type voltage gated calcium channels on the presynaptic terminals of primary nociceptive afferents in the dorsal horn of the spinal cord. This prevents the release of pain neurotransmitters such as glutamate, substance P, and CGRP. It does not act on opioid receptors, so it does not cause tolerance, respiratory depression, or dependence, but it must be delivered directly into cerebrospinal fluid because it does not cross the blood brain barrier.", "evidence_grade": "human_rct", "evidence_summary": "Three randomized placebo controlled trials in about 590 patients with severe refractory pain. With fast titration, pain scores improved 53.1% versus 18.1% in cancer or AIDS pain (n = 111) and 31.2% versus 6.0% in non-malignant pain (n = 255), but adverse effects were frequent. With slow titration (n = 220), improvement was 14.7% versus 7.2%, statistically significant but modest. Psychiatric and cognitive adverse events limit use.", "human_evidence": "Staats 2004 (n = 111, cancer or AIDS pain): mean pain improvement 53.1% versus 18.1% on placebo, with 52.9% of ziconotide patients responding, but dizziness, nausea, nystagmus, and confusion were common with rapid titration. Wallace 2006 (n = 255, non-malignant pain): 31.2% versus 6.0% improvement. Rauck 2006 (n = 220, slow titration over 3 weeks to a mean 0.29 mcg per hour): 14.7% versus 7.2% improvement, with fewer severe adverse events. Long term open label data show that a subset of patients maintain benefit for years.", "animal_evidence": "Ziconotide produced dose dependent analgesia in rodent models of acute, inflammatory, and neuropathic pain when given intrathecally, without tolerance on repeated dosing. Animal work also established the N-type calcium channel mechanism and the lack of opioid receptor activity.", "conditions": [], "literature_dosing": "FDA label (Prialt, DailyMed; intrathecal infusion through a programmable implanted or external microinfusion device, never intravenous): start at no more than 2.4 mcg per day (0.1 mcg per hour) and titrate by up to 2.4 mcg per day, no more than 2 to 3 times per week, to a recommended maximum of 19.2 mcg per day (0.8 mcg per hour) by day 21. The 25 mcg/mL strength is used undiluted; the 100 mcg/mL strength is diluted until a dose is established. The label carries a boxed warning for severe psychiatric symptoms and neurological impairment, and it is contraindicated with a history of psychosis.", "routes": [ "Continuous intrathecal infusion via an implanted or external microinfusion pump (only approved route)" ], "side_effects": [ "Boxed warning: severe psychiatric symptoms (hallucinations, paranoia, depression, suicidal thinking) and neurological impairment (confusion, decreased alertness)", "Dizziness (about 46% in trials), nausea, nystagmus, and abnormal gait", "Memory impairment and speech disorder", "Elevated creatine kinase, sometimes with muscle pain or weakness", "Urinary retention", "Meningitis related to the intrathecal delivery system rather than the drug" ], "interactions": [ "Additive central nervous system depression with opioids, benzodiazepines, antiepileptics, and sedatives; the label advises caution", "No pharmacokinetic drug interactions expected because ziconotide is cleared by peptidases in cerebrospinal fluid, not by liver enzymes" ], "contraindications": [ "Pre-existing history of psychosis", "Any condition where intrathecal administration is contraindicated (infection at the site, uncontrolled bleeding, spinal canal obstruction)", "Hypersensitivity to ziconotide" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Prialt, approved December 28, 2004) for severe chronic pain in patients who need intrathecal therapy and are intolerant of or refractory to other treatments. Supplied as sterile solution for intrathecal pumps; hospital pharmacies may dilute it for pump filling. Not on any 503A bulks list and not sold as a research chemical for human use.", "typical_cost": "Drug cost is several thousand USD per month at list, plus the cost of pump implantation and refills. It is almost always billed through insurance as part of an intrathecal therapy program rather than paid in cash.", "access_path": [ "Prescription and management by a pain specialist at a clinic or hospital that implants and refills intrathecal pumps.", "Not available through retail pharmacies, compounding pharmacies, or telehealth." ], "faqs": [ { "q": "Is ziconotide (Prialt) FDA approved, and what is it used for?", "a": "Yes. Prialt was approved in December 2004. Its label covers the management of severe chronic pain in adults for whom intrathecal therapy (drug delivered into the spinal fluid) is warranted and who are intolerant of or refractory to (not helped by) other treatment, such as systemic analgesics (pain medicines taken by mouth or injection), adjunctive therapies, or intrathecal morphine. It is a non-opioid N-type calcium channel blocker, which blocks pain signals in the spinal cord, given only into the spinal fluid.", "source_ids": [ "fda-prialt-label" ] }, { "q": "Does ziconotide actually work for chronic pain?", "a": "For some patients, yes. In the pivotal cancer and AIDS pain trial (n = 111), pain scores improved 53.1% on ziconotide versus 18.1% on placebo. In non-malignant pain (n = 255), 31.2% versus 6.0%. With the slower titration now recommended (n = 220), the difference was smaller, 14.7% versus 7.2%. Roughly a third to a half of patients get meaningful relief, and many stop because of side effects.", "source_ids": [ "staats-2004", "wallace-2006", "rauck-2006" ] }, { "q": "What are the side effects of ziconotide?", "a": "The label carries a boxed warning for severe psychiatric symptoms (hallucinations, paranoia, depression, suicidality) and neurological impairment (confusion, reduced alertness). Dizziness, nausea, nystagmus, unsteady gait, memory problems, and raised creatine kinase are common. Side effects were much more frequent with the fast titration used in the first trials and are reduced but not eliminated with slow titration.", "source_ids": [ "fda-prialt-label", "rauck-2006" ] }, { "q": "What is the ziconotide (Prialt) dose on the FDA label?", "a": "A continuous infusion into the cerebrospinal fluid through an implanted or external intrathecal pump, started at no more than 2.4 mcg per day and raised by up to 2.4 mcg per day no more than 2 to 3 times a week, to a recommended maximum of 19.2 mcg per day by day 21. Slow titration matters because of the boxed warning for psychiatric and neurological effects.", "source_ids": [ "fda-prialt-label" ] }, { "q": "How much does ziconotide cost?", "a": "The drug itself costs several thousand USD per month at list price, on top of the surgery to implant a pump and the cost of periodic refills. In practice it is used inside a hospital or pain clinic intrathecal program and billed through insurance; a cash pay route does not really exist.", "source_ids": [ "fda-prialt-label" ] }, { "q": "Is ziconotide banned by WADA?", "a": "No. Ziconotide is not on the WADA Prohibited List. It is not an opioid, not a stimulant, and has no known performance enhancing effect. Athletes using it should still declare it and check with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Ziconotide vs intrathecal morphine: which is better?", "a": "Both are first line intrathecal agents in the Polyanalgesic Consensus Conference guidelines. Morphine has a longer track record and is easier to titrate, but causes tolerance, respiratory depression, and granuloma at the catheter tip. Ziconotide does not cause tolerance or respiratory depression but has more psychiatric and cognitive side effects and a narrow therapeutic window. No large head to head randomized trial exists.", "source_ids": [ "pacc-2017", "fda-prialt-label" ] } ], "studies": [ { "pmid": "14709577", "title": "Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial", "year": 2004, "design": "Randomized, double blind, placebo controlled trial, 5 to 6 day titration", "n": 111, "population": "Adults with refractory pain from cancer or AIDS", "outcome": "Mean VAS pain improvement 53.1% versus 18.1% with placebo; 52.9% versus 17.5% responders; frequent neurological adverse events", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/14709577/" }, { "pmid": "22151630", "title": "Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial", "year": 2006, "design": "Randomized, double blind, placebo controlled trial", "n": 255, "population": "Adults with severe chronic non-malignant pain", "outcome": "Mean VAS pain improvement 31.2% versus 6.0% with placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22151630/" }, { "pmid": "16716870", "title": "A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain", "year": 2006, "design": "Randomized, double blind, placebo controlled trial, 3 week slow titration", "n": 220, "population": "Adults with severe chronic pain refractory to other therapy", "outcome": "Mean VAS pain improvement 14.7% versus 7.2% with placebo (p = 0.036); fewer serious adverse events than earlier fast titration trials", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16716870/" } ], "sources": [ { "id": "staats-2004", "type": "pubmed", "title": "Staats PS et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004", "url": "https://pubmed.ncbi.nlm.nih.gov/14709577/", "pmid": "14709577", "year": 2004 }, { "id": "wallace-2006", "type": "pubmed", "title": "Wallace MS et al. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/22151630/", "pmid": "22151630", "year": 2006 }, { "id": "rauck-2006", "type": "pubmed", "title": "Rauck RL et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage 2006", "url": "https://pubmed.ncbi.nlm.nih.gov/16716870/", "pmid": "16716870", "year": 2006 }, { "id": "pacc-2017", "type": "pubmed", "title": "Deer TR et al. The Polyanalgesic Consensus Conference (PACC): recommendations on intrathecal drug infusion systems best practices and guidelines. Neuromodulation 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28042904/", "pmid": "28042904", "year": 2017 }, { "id": "fda-prialt-label", "type": "fda", "title": "FDA prescribing information for Prialt (ziconotide) intrathecal infusion, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b025d8ed-937d-4597-9ad1-0b2f6e0ee5b1", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "calcitonin", "desmopressin", "cerebrolysin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 4, "seo": { "title": "Ziconotide (Prialt): uses, side effects, and dosing", "description": "Prialt is ziconotide, an intrathecal non-opioid pain drug for severe chronic pain. FDA label use, slow dose titration, psychiatric warning, and side effects.", "h1": "Ziconotide (Prialt)" } }, { "slug": "enfuvirtide", "name": "Enfuvirtide", "aliases": [ "Fuzeon", "T-20", "pentafuside", "DP-178" ], "class": "HIV-1 fusion inhibitor (synthetic 36 amino acid peptide mimicking the gp41 HR2 region)", "one_liner": "FDA approved HIV injection that stops the virus entering cells, for drug-resistant HIV; cuts viral load an extra 0.8 to 0.9 log10 (6 to 8 fold) at 24 weeks.", "summary": "Enfuvirtide is an FDA approved twice daily peptide injection given under the skin (Fuzeon, approved March 2003) that blocks HIV-1 from fusing with, and so entering, CD4 cells (the immune cells HIV infects), reserved for treatment experienced patients whose virus is resistant to other drugs. In the two TORO phase 3 trials (1,005 people combined), adding enfuvirtide to an optimized regimen lowered HIV RNA (the amount of virus in the blood) by an extra 0.78 to 0.93 log10 copies per mL at 24 weeks, roughly a 6 to 8 fold larger drop, at the cost of injection site reactions in nearly every patient. It is rarely used today because newer oral and long acting drugs exist, but it remains a legitimate prescription antiretroviral (HIV medicine).", "mechanism": "Enfuvirtide is a peptide copy of part of the HR2 region of the HIV-1 envelope glycoprotein gp41. It binds the HR1 region of gp41 during the conformational change that follows CD4 and coreceptor binding, blocking formation of the six-helix bundle that pulls the viral and cell membranes together. This stops the virus entering the cell. It has no activity against HIV-2 and is not affected by resistance to reverse transcriptase, protease, or integrase inhibitors.", "evidence_grade": "human_rct", "evidence_summary": "Two randomized open label phase 3 trials (TORO 1, n = 501, and TORO 2, n = 504) in heavily treatment experienced patients showed that enfuvirtide plus an optimized background regimen reduced HIV RNA by 1.70 and 1.43 log10 copies per mL at 24 weeks versus 0.76 and 0.65 with background alone. Pooled 48 week results confirmed durable benefit. Injection site reactions occurred in about 98% of patients and bacterial pneumonia was more frequent.", "human_evidence": "TORO 1 (North and South America, n = 501): mean change in HIV RNA at 24 weeks minus 1.696 log10 with enfuvirtide versus minus 0.764 log10 with optimized background alone (difference 0.93 log10); CD4 count rose 76 versus 32 cells per microliter. TORO 2 (Europe and Australia, n = 504): minus 1.43 versus minus 0.65 log10 (difference 0.78 log10). At 48 weeks in the pooled analysis, 30.4% of enfuvirtide patients had HIV RNA under 400 copies per mL versus 12.0% of controls. Injection site reactions occurred in 98% of enfuvirtide recipients and pneumonia in 4.7 versus 0.6 events per 100 patient years.", "animal_evidence": "Preclinical work characterized peptide inhibition of HIV-1 fusion in cell culture and pharmacokinetics in animals. Because HIV-1 does not infect standard laboratory animals, efficacy was established in humans rather than in animal disease models.", "conditions": [], "literature_dosing": "FDA label (Fuzeon, 2019, via Drugs@FDA): adults, 90 mg (1 mL) injected subcutaneously twice daily into the upper arm, anterior thigh, or abdomen; pediatric patients weighing at least 11 kg, 2 mg/kg twice daily up to a maximum of 90 mg twice daily, with the dose adjusted as weight changes. It is always used in combination with other antiretroviral agents in treatment experienced patients with ongoing HIV-1 replication.", "routes": [ "Subcutaneous injection twice daily" ], "side_effects": [ "Injection site reactions in about 98% of patients (pain, induration, erythema, nodules, cysts); about 4% discontinue for this reason", "Increased rate of bacterial pneumonia (4.7 versus 0.6 events per 100 patient years in TORO)", "Hypersensitivity reactions (rash, fever, nausea, hypotension, elevated transaminases) in under 1%; do not rechallenge", "Peripheral neuropathy, insomnia, depression, and decreased appetite reported more often than with background regimen alone", "Eosinophilia" ], "interactions": [ "No significant pharmacokinetic interactions identified; enfuvirtide is a peptide broken down by catabolism and does not use cytochrome P450 enzymes", "Studied without interaction with ritonavir, saquinavir plus ritonavir, and rifampin" ], "contraindications": [ "Known hypersensitivity to enfuvirtide or any component of the product", "Not for use as monotherapy or in treatment naive patients (label indication is treatment experienced patients with evidence of ongoing replication)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Fuzeon, approved March 13, 2003, the first HIV fusion inhibitor). Drugs@FDA lists the Fuzeon product's marketing status as discontinued as of the last verified date; the approval itself has not been withdrawn. It is not on any 503A bulks list and is not a research chemical.", "typical_cost": "List price is over 3,000 USD per month, making it one of the most expensive antiretrovirals. It is typically covered by insurance, Medicaid, or AIDS Drug Assistance Programs when a resistance profile justifies its use.", "access_path": [ "Prescription from an HIV specialist, filled by a specialty pharmacy as Fuzeon.", "Not available through compounding pharmacies, telehealth peptide clinics, or research chemical sellers." ], "faqs": [ { "q": "Is enfuvirtide (Fuzeon) FDA approved, and what is it used for?", "a": "Yes. Fuzeon was approved in March 2003 as the first HIV fusion inhibitor (a drug that stops the virus from entering cells). Its label covers HIV-1 infection in treatment experienced patients with evidence of HIV-1 replication (the virus still multiplying) despite ongoing antiretroviral therapy, always in combination with other antiretroviral (HIV) agents. Drugs@FDA, FDA's database of approved drugs, now lists the product's marketing status as discontinued, although the approval has not been withdrawn.", "source_ids": [ "fda-fuzeon-label", "fda-fuzeon-drugsatfda" ] }, { "q": "Does enfuvirtide work for drug-resistant HIV?", "a": "Yes. In TORO 1 (n = 501) adding enfuvirtide to an optimized background regimen lowered HIV RNA by 1.70 log10 at 24 weeks versus 0.76 log10 for background alone, and in TORO 2 (n = 504) by 1.43 versus 0.65 log10. At 48 weeks, 30% of enfuvirtide patients had viral loads under 400 copies per mL versus 12% of controls. The benefit was largest when at least two other active drugs were in the regimen.", "source_ids": [ "toro-1", "toro-2", "toro-48wk" ] }, { "q": "What are the side effects of enfuvirtide?", "a": "Injection site reactions are almost universal (98% in the TORO trials), with pain, hardening, redness, and nodules that can persist for days. Bacterial pneumonia was about eight times more frequent than in controls. Rare hypersensitivity reactions with rash, fever, and low blood pressure occur and the drug should not be restarted after one. Peripheral neuropathy, insomnia, and eosinophilia were also reported.", "source_ids": [ "toro-1", "fda-fuzeon-label" ] }, { "q": "What is the enfuvirtide (Fuzeon) dose on the FDA label?", "a": "90 mg injected under the skin twice daily in adults, into the upper arm, anterior thigh, or abdomen with rotating sites. Children weighing at least 11 kg receive 2 mg/kg twice daily, up to 90 mg twice daily. It is always combined with other antiretroviral drugs. The most common label adverse reactions are local injection site reactions, diarrhea, nausea, and fatigue.", "source_ids": [ "fda-fuzeon-label" ] }, { "q": "How much does enfuvirtide cost?", "a": "More than 3,000 USD per month at list price, which is why it is reserved for patients whose resistance profile leaves few options. Insurance, Medicaid, and state AIDS Drug Assistance Programs generally cover it when prescribed by an HIV specialist with a documented need.", "source_ids": [ "fda-fuzeon-label" ] }, { "q": "Is enfuvirtide banned by WADA?", "a": "No. Enfuvirtide is not on the WADA Prohibited List. Antiretroviral drugs are not prohibited and have no performance enhancing effect.", "source_ids": [ "wada-list" ] }, { "q": "Why is enfuvirtide rarely used today?", "a": "Because newer drugs achieve similar or better results without twice daily injections. Since 2007 integrase inhibitors, second generation protease and NNRTI drugs, and newer entry inhibitors have given most treatment experienced patients oral or long acting options. Enfuvirtide is still on the label for patients with multidrug resistant virus who cannot use those agents.", "source_ids": [ "toro-48wk", "fda-fuzeon-label" ] } ], "studies": [ { "pmid": "12637625", "title": "Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America (TORO 1)", "year": 2003, "design": "Randomized, open label, controlled phase 3 trial, 24 week primary analysis", "n": 501, "population": "Treatment experienced adults with HIV-1 RNA of at least 5,000 copies per mL and resistance to three drug classes", "outcome": "HIV RNA change minus 1.696 log10 with enfuvirtide plus optimized background versus minus 0.764 log10 with background alone at 24 weeks", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/12637625/" }, { "pmid": "12773645", "title": "Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia (TORO 2)", "year": 2003, "design": "Randomized, open label, controlled phase 3 trial, 24 week primary analysis", "n": 504, "population": "Treatment experienced adults with multidrug resistant HIV-1", "outcome": "HIV RNA change minus 1.43 log10 versus minus 0.65 log10 at 24 weeks; CD4 gain 65 versus 38 cells per microliter", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/12773645/" }, { "pmid": "16280694", "title": "Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials", "year": 2005, "design": "Pooled 48 week analysis of two randomized trials", "n": 995, "population": "Treatment experienced adults from TORO 1 and TORO 2", "outcome": "HIV RNA under 400 copies per mL in 30.4% with enfuvirtide versus 12.0% with background alone at 48 weeks; benefit durable across subgroups", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/16280694/" } ], "sources": [ { "id": "toro-1", "type": "pubmed", "title": "Lalezari JP et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003 (TORO 1)", "url": "https://pubmed.ncbi.nlm.nih.gov/12637625/", "pmid": "12637625", "year": 2003 }, { "id": "toro-2", "type": "pubmed", "title": "Lazzarin A et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 2003 (TORO 2)", "url": "https://pubmed.ncbi.nlm.nih.gov/12773645/", "pmid": "12773645", "year": 2003 }, { "id": "toro-48wk", "type": "pubmed", "title": "Nelson M et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the TORO 1 and 2 trials. J Acquir Immune Defic Syndr 2005", "url": "https://pubmed.ncbi.nlm.nih.gov/16280694/", "pmid": "16280694", "year": 2005 }, { "id": "fda-fuzeon-label", "type": "fda", "title": "FDA prescribing information for Fuzeon (enfuvirtide) for injection, 2019 label via Drugs@FDA", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021481s033lbl.pdf", "year": 2019 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-fuzeon-drugsatfda", "type": "fda", "title": "Drugs@FDA: Fuzeon (enfuvirtide), NDA 021481, product and marketing status", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021481", "year": 2026 } ], "related": [ "thymosin-alpha-1", "ll-37", "thymulin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Enfuvirtide (Fuzeon): uses, side effects, and dosing", "description": "Fuzeon is enfuvirtide, an injectable HIV-1 fusion inhibitor for treatment experienced patients. FDA label use and dose, side effects, and availability.", "h1": "Enfuvirtide (Fuzeon)" } }, { "slug": "vosoritide", "name": "Vosoritide", "aliases": [ "Voxzogo", "BMN 111", "modified C-type natriuretic peptide", "CNP analog" ], "class": "C-type natriuretic peptide analog (39 amino acid peptide resistant to neprilysin degradation)", "one_liner": "FDA approved daily injection for achondroplasia that increases growth velocity by about 1.6 cm per year over placebo in children.", "summary": "Vosoritide is an FDA approved once daily subcutaneous peptide (Voxzogo, approved November 2021) that increases linear growth in children with achondroplasia whose growth plates are still open. In a 52 week phase 3 trial of 121 children, annualized growth velocity was 1.57 cm per year higher than placebo, and open label extension data show the effect persisting for at least 2 years. It is a specialty prescription drug for a genetic condition, not a research peptide, and there is no evidence it increases height in people without achondroplasia or with closed growth plates.", "mechanism": "Achondroplasia is caused by a gain of function mutation in FGFR3 that suppresses chondrocyte proliferation in the growth plate through the MAPK pathway. Vosoritide is a C-type natriuretic peptide analog that binds natriuretic peptide receptor B on chondrocytes, raising cyclic GMP, which inhibits the MAPK pathway downstream of FGFR3 and restores chondrocyte proliferation and differentiation. The analog is modified to resist neprilysin, giving a longer half life than native CNP.", "evidence_grade": "human_rct", "evidence_summary": "One randomized, double blind, placebo controlled phase 3 trial (n = 121, 52 weeks) in children 5 to under 18 with achondroplasia showed annualized growth velocity 1.57 cm per year higher with vosoritide 15 mcg per kg daily than with placebo. A phase 2 dose finding study (n = 35) and a 2 year open label extension showed sustained effect and no new safety signals. Approval was expanded to all ages with open growth plates in 2023 based on additional infant and toddler data.", "human_evidence": "Savarirayan 2020 (phase 3, n = 121, ages 5 to under 18, 52 weeks): annualized growth velocity increased from baseline by 1.57 cm per year (95% CI 1.22 to 1.93) more with vosoritide 15 mcg per kg daily than with placebo; injection site reactions were common but mild and transient hypotension was rare. Savarirayan 2019 (phase 2, n = 35, 6 to 24 months): dose dependent growth velocity increase, with 15 mcg per kg selected. Savarirayan 2021 (open label extension, 2 years): growth velocity gains persisted and the body proportion ratio improved modestly.", "animal_evidence": "In mouse models of achondroplasia, CNP analogs restored bone growth and skull shape by counteracting FGFR3 signaling. Toxicology studies in juvenile monkeys and rodents examined effects on blood pressure and bone. The neprilysin resistant design of vosoritide was developed from this preclinical work.", "conditions": [], "literature_dosing": "FDA label (Voxzogo, DailyMed): one subcutaneous injection daily at a dose set by actual body weight from a table in the label, from 0.096 mg at 3 kg up to 0.8 mg at 90 kg or more (for example 0.4 mg at 22 to 32 kg and 0.7 mg at 60 to 89 kg), adjusted as weight changes and stopped permanently once the growth plates close. To lower the risk of low blood pressure, the child should have adequate food intake and drink about 240 to 300 mL of fluid in the hour before each dose. The phase 3 trial used 15 mcg/kg daily.", "routes": [ "Subcutaneous injection once daily" ], "side_effects": [ "Injection site reactions (erythema, swelling, urticaria) in most patients, usually mild", "Transient decreases in blood pressure with dizziness or nausea, typically within 90 minutes of a dose", "Vomiting, arthralgia, and gastroenteritis reported in trials", "Increased alkaline phosphatase (marker of bone turnover)", "Long term effects on final adult height and body proportions are still being characterized" ], "interactions": [ "No formal drug interaction studies; vosoritide is degraded by peptidases and is not expected to interact through cytochrome P450 enzymes", "Theoretical additive blood pressure lowering with antihypertensive agents (not studied)" ], "contraindications": [ "None listed on the label, but the drug is only indicated while epiphyses are open; it has no effect after growth plates close", "Not indicated for short stature that is not caused by achondroplasia" ], "wada_status": "unclear", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Voxzogo, approved November 19, 2021 for achondroplasia in children 5 and older with open epiphyses; expanded in October 2023 to all ages with open epiphyses). Commercially available, so it is not eligible for routine compounding and is not on any 503A bulks list. Some research chemical sellers list it, but those products are not lawful for human use and have no place in achondroplasia care.", "typical_cost": "List price is roughly 300,000 USD per year or more depending on weight based dose. It is covered by most insurers and Medicaid for children with confirmed achondroplasia, with manufacturer assistance programs available.", "access_path": [ "Prescription from a pediatric endocrinologist or geneticist, dispensed through a specialty pharmacy as Voxzogo.", "Not available through compounding pharmacies or telehealth peptide clinics; research chemical products are not lawful for human use." ], "faqs": [ { "q": "Is vosoritide (Voxzogo) FDA approved, and what is it used for?", "a": "Yes. Voxzogo was approved in November 2021, and its label covers increasing linear growth in children with achondroplasia whose growth plates are still open; the 2023 expansion removed the lower age limit. It is an accelerated approval based on annualized growth velocity, so continued approval may depend on confirmatory trials. It is not approved for other causes of short stature or for adults, and it is dispensed by specialty pharmacies on prescription.", "source_ids": [ "fda-voxzogo-approval", "fda-voxzogo-label" ] }, { "q": "Does vosoritide work for achondroplasia?", "a": "Yes, for growth velocity. In the phase 3 trial of 121 children aged 5 to 17, those on vosoritide 15 mcg per kg daily grew 1.57 cm per year faster than those on placebo over 52 weeks, roughly doubling their annual growth rate. In the 2 year extension the gain persisted. The trial measured growth speed, not final adult height, which is still being followed.", "source_ids": [ "savarirayan-2020", "savarirayan-2021" ] }, { "q": "Can vosoritide make adults or non-achondroplasia children taller?", "a": "No evidence supports that. Vosoritide works by counteracting FGFR3 overactivity at open growth plates, so it has no target once epiphyses have closed, which is why the label limits use to children with open epiphyses. It has not been tested in idiopathic short stature or in adults, and it is not approved or studied for cosmetic height gain.", "source_ids": [ "fda-voxzogo-label", "savarirayan-2019" ] }, { "q": "What are the side effects of vosoritide?", "a": "Injection site reactions such as redness and swelling occur in most children and are usually mild. Transient drops in blood pressure with dizziness or nausea can happen within about 90 minutes of a dose, which is why the label advises giving it with food and fluids. Vomiting, joint pain, and raised alkaline phosphatase were also reported. No serious safety signal emerged over 2 years of extension data.", "source_ids": [ "savarirayan-2020", "savarirayan-2021", "fda-voxzogo-label" ] }, { "q": "What is the vosoritide (Voxzogo) dose on the FDA label?", "a": "One injection under the skin each day, at a dose read from the label's body weight table (from 0.096 mg at 3 kg to 0.8 mg at 90 kg or more), adjusted as the child grows. The child should eat and drink about 240 to 300 mL of fluid in the hour before each dose to limit drops in blood pressure. Treatment stops permanently once the growth plates close.", "source_ids": [ "fda-voxzogo-label" ] }, { "q": "How much does vosoritide cost?", "a": "Roughly 300,000 USD per year or more at list price, scaling with the weight based dose. Commercial insurers and Medicaid generally cover it for children with a confirmed diagnosis of achondroplasia, and the manufacturer runs a patient assistance program. Prices verified on the last verified date.", "source_ids": [ "fda-voxzogo-approval" ] }, { "q": "Is vosoritide banned by WADA?", "a": "It is not named on the WADA Prohibited List, and as an approved drug it is not covered by section S0. Whether it falls under the growth factor language in section S2 is not spelled out, so PeptideAgent marks it unclear. Athletes with achondroplasia prescribed vosoritide should seek a therapeutic use exemption through their anti-doping organization before competing.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "32891212", "title": "Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial", "year": 2020, "design": "Randomized, double blind, placebo controlled phase 3 trial, 52 weeks", "n": 121, "population": "Children aged 5 to under 18 with genetically confirmed achondroplasia and open epiphyses", "outcome": "Annualized growth velocity 1.57 cm per year higher with vosoritide 15 mcg per kg daily than with placebo (95% CI 1.22 to 1.93)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/32891212/" }, { "pmid": "31269546", "title": "C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia", "year": 2019, "design": "Phase 2, open label, dose finding study with 6 to 24 month follow up", "n": 35, "population": "Children aged 5 to 14 with achondroplasia", "outcome": "Dose dependent increase in annualized growth velocity, sustained at 15 mcg per kg; mild injection site reactions and transient hypotension", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/31269546/" }, { "pmid": "34341520", "title": "Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study", "year": 2021, "design": "Open label extension of the phase 3 trial, 2 years", "n": 119, "population": "Children with achondroplasia who completed the phase 3 trial", "outcome": "Growth velocity gains persisted through 2 years; children switched from placebo matched the original treatment group; no new safety concerns", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/34341520/" } ], "sources": [ { "id": "savarirayan-2020", "type": "pubmed", "title": "Savarirayan R et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32891212/", "pmid": "32891212", "year": 2020 }, { "id": "savarirayan-2019", "type": "pubmed", "title": "Savarirayan R et al. C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. N Engl J Med 2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31269546/", "pmid": "31269546", "year": 2019 }, { "id": "savarirayan-2021", "type": "pubmed", "title": "Savarirayan R et al. Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Genet Med 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34341520/", "pmid": "34341520", "year": 2021 }, { "id": "fda-voxzogo-approval", "type": "fda", "title": "FDA news release: FDA approves first drug to improve growth in children with most common form of dwarfism (November 2021)", "url": "https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-improve-growth-children-most-common-form-dwarfism", "year": 2021 }, { "id": "fda-voxzogo-label", "type": "fda", "title": "FDA prescribing information for Voxzogo (vosoritide) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=228e8560-04a4-4bb1-a81f-29531a9e4d27", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "teriparatide", "abaloparatide", "igf-1-lr3" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Vosoritide (Voxzogo): uses, side effects, and dosing", "description": "Voxzogo is vosoritide, a daily injection to increase linear growth in children with achondroplasia and open growth plates. FDA label use and weight-based dose.", "h1": "Vosoritide (Voxzogo)" } }, { "slug": "terlipressin", "name": "Terlipressin", "aliases": [ "Terlivaz", "Glypressin", "triglycyl lysine vasopressin", "tGLVP" ], "class": "Synthetic vasopressin analog prodrug (12 amino acid peptide, converted to lysine vasopressin), V1 receptor agonist", "one_liner": "FDA approved hospital IV drug for hepatorenal syndrome (kidney failure from advanced liver disease); reverses it in about 32% versus 17% with albumin alone.", "summary": "Terlipressin is an FDA approved intravenous vasopressin analog, a lab-made relative of a hormone that tightens blood vessels (Terlivaz, approved September 2022), used in hospital, with albumin (a blood protein given by drip), to improve kidney function in adults with hepatorenal syndrome (kidney failure caused by advanced liver disease) and rapidly worsening kidney function. In the CONFIRM trial of 300 patients it achieved verified reversal of hepatorenal syndrome in 32% of patients versus 17% with placebo, but it carries a boxed warning, FDA's most serious label warning, for serious or fatal respiratory failure and did not improve 90 day survival. It is strictly an inpatient drug, not something dispensed or compounded for outpatient use.", "mechanism": "Terlipressin is a prodrug that is slowly cleaved by tissue peptidases to release lysine vasopressin. The active hormone constricts splanchnic arterioles through V1 receptors, which reduces the portal hypertension driven splanchnic vasodilation that underlies hepatorenal syndrome. Redirecting blood volume to the systemic circulation raises mean arterial pressure and renal perfusion, so glomerular filtration improves. It also has weak V2 activity, which can cause fluid retention.", "evidence_grade": "human_rct", "evidence_summary": "Three randomized placebo controlled trials in type 1 hepatorenal syndrome, all with albumin in both arms. CONFIRM (n = 300) showed verified HRS reversal in 32% versus 17%. REVERSE (n = 196) showed confirmed HRS reversal in 19.6% versus 13.1%, not statistically significant, though creatinine fell more with terlipressin. The 2008 trial (n = 112) showed HRS reversal in 34% versus 13%. None showed a survival benefit, and respiratory failure was more common with terlipressin in CONFIRM (10% versus 3%).", "human_evidence": "CONFIRM 2021 (n = 300, 2:1 randomization): verified reversal of hepatorenal syndrome (two consecutive serum creatinine values of 1.5 mg per dL or less at least 2 hours apart, alive without renal replacement therapy for at least 10 days) in 32% with terlipressin versus 17% with placebo (p = 0.006); death by day 90 was 51% versus 45%; respiratory failure occurred in 10% versus 3%. REVERSE 2016 (n = 196): confirmed HRS reversal 19.6% versus 13.1% (p = 0.22), with greater improvement in creatinine in the terlipressin group. Sanyal 2008 (n = 112): treatment success 25% versus 12.5% and HRS reversal 34% versus 13%.", "animal_evidence": "Animal pharmacology established V1 mediated splanchnic vasoconstriction, reduced portal pressure, and slow release of lysine vasopressin from the prodrug. Efficacy in hepatorenal syndrome was established in human trials rather than animal disease models.", "conditions": [], "literature_dosing": "FDA label (Terlivaz, DailyMed; intravenous, in hospital): 0.85 mg (1 vial) every 6 hours on days 1 to 3. On day 4, if serum creatinine has fallen at least 30% from baseline, continue 0.85 mg every 6 hours; if it has fallen less than 30%, the dose may be increased to 1.7 mg (2 vials) every 6 hours; if it is at or above baseline, stop. Treatment continues until 24 hours after two consecutive creatinine values of 1.5 mg/dL or less at least 2 hours apart, or a maximum of 14 days. Oxygen saturation is checked before starting and monitored throughout because of a boxed warning for serious or fatal respiratory failure.", "routes": [ "Intravenous bolus every 6 hours (US label)", "Continuous intravenous infusion (studied outside the US)" ], "side_effects": [ "Boxed warning: serious or fatal respiratory failure (10% versus 3% in CONFIRM), highest risk in patients with volume overload or grade 3 acute-on-chronic liver failure", "Abdominal pain, nausea, and diarrhea", "Ischemic events including myocardial, mesenteric, peripheral, and skin ischemia", "Bradycardia and hypertension", "Fluid overload and hyponatremia (weak V2 activity)", "Dyspnea and pleural effusion" ], "interactions": [ "Other vasoconstrictors or drugs that cause bradycardia (beta blockers): additive cardiovascular effects; the label advises caution", "Albumin: used together by design; excessive albumin volume increases the risk of respiratory failure", "QT prolonging drugs: terlipressin may prolong the QT interval" ], "contraindications": [ "Hypoxia (oxygen saturation under 90%) or worsening respiratory symptoms", "Ongoing coronary, peripheral, or mesenteric ischemia", "Not recommended when serum creatinine is 5 mg per dL or higher, because benefit is unlikely", "Pregnancy (uterine contraction and ischemia in animal studies)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Terlivaz, approved September 14, 2022 for hepatorenal syndrome with rapid reduction in kidney function), administered intravenously in hospital. Widely used in Europe for decades before US approval. Commercially available, so not eligible for routine compounding and not on any 503A bulks list. Not a research chemical.", "typical_cost": "Unknown at the per patient level; it is a hospital administered drug billed as part of an inpatient admission for cirrhosis and kidney failure. List price per vial is in the low thousands of USD and a course runs several days.", "access_path": [ "Hospital administration under a hepatologist or intensivist for a confirmed diagnosis of hepatorenal syndrome.", "Not available through retail pharmacies, compounding pharmacies, or telehealth." ], "faqs": [ { "q": "Is terlipressin (Terlivaz) FDA approved, and what is it used for?", "a": "Yes, since September 14, 2022. The Terlivaz label covers improving kidney function in adults with hepatorenal syndrome (kidney failure caused by advanced liver disease) with rapid reduction in kidney function; patients with serum creatinine, a blood marker that rises as kidneys fail, above 5 mg/dL are unlikely to benefit. It had been used in Europe, Asia, and Australia for many years before the US approval, which followed the CONFIRM trial.", "source_ids": [ "fda-terlivaz-approval", "fda-terlivaz-label", "confirm-2021" ] }, { "q": "Does terlipressin work for hepatorenal syndrome?", "a": "It improves kidney function in a minority of patients. In CONFIRM (n = 300), 32% of patients on terlipressin plus albumin had verified reversal of hepatorenal syndrome versus 17% on placebo plus albumin. An earlier trial (n = 112) found reversal in 34% versus 13%. However, 90 day survival was not improved (51% versus 45% mortality in CONFIRM), so the drug is a bridge to recovery or transplant rather than a cure.", "source_ids": [ "confirm-2021", "sanyal-2008" ] }, { "q": "What are the side effects of terlipressin?", "a": "The most serious is respiratory failure, which occurred in 10% of terlipressin patients versus 3% on placebo in CONFIRM and is the subject of a boxed warning, especially in patients with fluid overload or severe acute-on-chronic liver failure. Ischemic events (heart, gut, limbs, skin), abdominal pain, nausea, diarrhea, bradycardia, and fluid retention also occur. Patients are monitored in hospital for oxygen saturation and volume status.", "source_ids": [ "confirm-2021", "fda-terlivaz-label" ] }, { "q": "What is the terlipressin (Terlivaz) dose on the FDA label?", "a": "0.85 mg by intravenous bolus every 6 hours for days 1 to 3. On day 4 the dose stays the same if creatinine has fallen at least 30%, may rise to 1.7 mg every 6 hours if it has fallen less, and is stopped if creatinine is at or above baseline. It continues until 24 hours after two creatinine values of 1.5 mg/dL or less, for at most 14 days, with oxygen levels monitored because of the respiratory failure warning.", "source_ids": [ "fda-terlivaz-label" ] }, { "q": "How much does terlipressin cost?", "a": "It is an inpatient hospital drug, so patients rarely see a direct price; the cost is folded into the hospital admission and billed to insurance or Medicaid. Per vial list pricing is in the low thousands of USD and a typical course lasts several days. There is no cash pay or outpatient channel.", "source_ids": [ "fda-terlivaz-label" ] }, { "q": "Is terlipressin banned by WADA?", "a": "No. Terlipressin is not on the WADA Prohibited List and has no performance enhancing use. Vasopressin analogs in general are not prohibited.", "source_ids": [ "wada-list" ] }, { "q": "Terlipressin vs vasopressin or octreotide plus midodrine for hepatorenal syndrome?", "a": "Terlipressin is the only agent with randomized placebo controlled evidence of reversing hepatorenal syndrome. Before its US approval, US hospitals typically used octreotide plus midodrine with albumin, or norepinephrine in intensive care, largely on the basis of small studies. International guidelines list terlipressin plus albumin as first line; norepinephrine is an alternative where terlipressin is unavailable or in intensive care settings.", "source_ids": [ "confirm-2021", "reverse-2016" ] } ], "studies": [ { "pmid": "33657294", "title": "Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM)", "year": 2021, "design": "Randomized, double blind, placebo controlled phase 3 trial, 2:1 allocation, up to 14 days of treatment", "n": 300, "population": "Adults with cirrhosis, ascites, and type 1 hepatorenal syndrome (creatinine doubling to at least 2.25 mg per dL)", "outcome": "Verified HRS reversal 32% versus 17% (p = 0.006); 90 day mortality 51% versus 45%; respiratory failure 10% versus 3%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/33657294/" }, { "pmid": "26896734", "title": "Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1 (REVERSE)", "year": 2016, "design": "Randomized, double blind, placebo controlled phase 3 trial", "n": 196, "population": "Adults with cirrhosis and type 1 hepatorenal syndrome", "outcome": "Confirmed HRS reversal 19.6% versus 13.1% (not significant); greater decrease in serum creatinine with terlipressin", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/26896734/" }, { "pmid": "18471513", "title": "A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome", "year": 2008, "design": "Randomized, double blind, placebo controlled trial, up to 14 days", "n": 112, "population": "Adults with type 1 hepatorenal syndrome in North America", "outcome": "Treatment success 25% versus 12.5%; HRS reversal 34% versus 13% (p = 0.008); no difference in overall survival", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/18471513/" } ], "sources": [ { "id": "confirm-2021", "type": "pubmed", "title": "Wong F et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med 2021 (CONFIRM)", "url": "https://pubmed.ncbi.nlm.nih.gov/33657294/", "pmid": "33657294", "year": 2021 }, { "id": "reverse-2016", "type": "pubmed", "title": "Boyer TD et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology 2016 (REVERSE)", "url": "https://pubmed.ncbi.nlm.nih.gov/26896734/", "pmid": "26896734", "year": 2016 }, { "id": "sanyal-2008", "type": "pubmed", "title": "Sanyal AJ et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18471513/", "pmid": "18471513", "year": 2008 }, { "id": "fda-terlivaz-approval", "type": "fda", "title": "Drugs@FDA: Terlivaz (terlipressin) NDA 022231", "url": "https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022231", "year": 2022 }, { "id": "fda-terlivaz-label", "type": "fda", "title": "FDA prescribing information for Terlivaz (terlipressin) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a35b86c-f451-4fac-8499-43019e4da354", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "vasopressin", "desmopressin", "octreotide", "oxytocin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Terlipressin (Terlivaz): uses, side effects, and dosing", "description": "Terlivaz is terlipressin, an IV hospital drug to improve kidney function in hepatorenal syndrome. FDA label use, dose schedule, respiratory failure warning.", "h1": "Terlipressin (Terlivaz)" } }, { "slug": "cosyntropin", "name": "Cosyntropin", "aliases": [ "Cortrosyn", "tetracosactide", "tetracosactrin", "Synacthen", "ACTH 1-24", "synthetic ACTH" ], "class": "Synthetic 24 amino acid N-terminal fragment of adrenocorticotropic hormone (ACTH), melanocortin 2 receptor agonist", "one_liner": "FDA approved diagnostic peptide for the ACTH stimulation test, which checks whether the adrenal glands make enough cortisol; prohibited by WADA in sport.", "summary": "Cosyntropin is an FDA approved synthetic fragment of ACTH, the pituitary hormone that tells the adrenal glands to make cortisol, used as a single 250 mcg injection to test whether the adrenal glands can produce cortisol; a stimulated cortisol below about 18 mcg per dL (500 nmol per L) supports adrenal insufficiency (adrenal glands that make too little cortisol). It is a diagnostic agent given in clinics and hospitals, not a treatment, and it has been a generic drug since the 1970s. Because it stimulates cortisol release it is prohibited in sport under WADA section S2, the anti-doping class for peptide hormones.", "mechanism": "Cosyntropin contains the first 24 amino acids of ACTH, which carry the full biological activity of the 39 amino acid native hormone. It binds the melanocortin 2 receptor on adrenal cortex cells and stimulates synthesis and release of cortisol (and to a lesser extent aldosterone and adrenal androgens) within minutes. A healthy adrenal gland roughly doubles cortisol output within 30 to 60 minutes; an atrophied or destroyed gland cannot.", "evidence_grade": "human_observational", "evidence_summary": "The cosyntropin stimulation test is the standard confirmatory test for primary adrenal insufficiency in the Endocrine Society guideline, based on decades of diagnostic accuracy studies rather than randomized trials. A 2016 systematic review and meta-analysis of 30 studies found the standard 250 mcg test performs well for primary adrenal insufficiency but has limited sensitivity (about 64%) for secondary adrenal insufficiency, where the adrenal glands may still respond to a supraphysiologic dose. There is no treatment claim to grade; the evidence grade reflects diagnostic accuracy cohorts.", "human_evidence": "Ospina 2016 (systematic review, 30 diagnostic accuracy studies): for secondary adrenal insufficiency the standard dose test had pooled sensitivity of about 64% and the 1 mcg low dose test about 92%, with similar specificity; both tests reliably identify primary adrenal insufficiency. The Endocrine Society 2016 guideline recommends the 250 mcg test as the gold standard confirmatory test with a peak cortisol cutoff below 500 nmol per L (18 mcg per dL), noting that the cutoff depends on the assay used. A 2021 Lancet review summarizes the same diagnostic approach.", "animal_evidence": "Animal studies established that the 1 to 24 fragment retains the full steroidogenic activity of ACTH. No animal disease model is relevant to its diagnostic use.", "conditions": [], "literature_dosing": "FDA label (Cortrosyn, DailyMed; diagnostic use only): adults, 0.25 mg by intravenous or intramuscular injection; pediatric patients, 0.125 mg from birth to under 2 years and 0.25 mg from 2 to 17 years. Serum cortisol is drawn at baseline and exactly 30 and 60 minutes after the injection. The label advises stopping glucocorticoids and spironolactone on the test day (longer for long acting glucocorticoids) and stopping estrogen containing drugs 4 to 6 weeks before testing, because they distort cortisol results.", "routes": [ "Intravenous or intramuscular single injection (diagnostic)", "Intravenous infusion over 4 to 8 hours (prolonged test)" ], "side_effects": [ "Rare hypersensitivity reactions including anaphylaxis, more likely in patients with prior ACTH allergy", "Flushing, bradycardia, tachycardia, or hypertension reported rarely", "Peripheral edema and rash reported rarely", "Transient rise in cortisol is the intended effect, not an adverse one" ], "interactions": [ "Glucocorticoids (hydrocortisone, prednisone, dexamethasone) and other steroids alter baseline and stimulated cortisol measurement; the label and guideline advise timing or withholding them before the test", "Oral estrogens raise cortisol binding globulin and total cortisol, which can produce a falsely reassuring result", "Spironolactone may interfere with cortisol assays" ], "contraindications": [ "History of hypersensitivity to cosyntropin or ACTH", "Not for use as a treatment (the therapeutic ACTH products are separate)" ], "wada_status": "prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved diagnostic drug (Cortrosyn, approved 1970; generics available). It is a diagnostic agent, not a therapy, so there is no compounding or telehealth market and it is not on any 503A bulks list. Not sold as a research chemical for human use in any meaningful volume.", "typical_cost": "One vial per test, usually billed as part of an office or hospital diagnostic procedure rather than dispensed. Cash prices for a generic 0.25 mg vial run in the low hundreds of USD.", "access_path": [ "Administered by a clinician in an endocrinology clinic, hospital, or lab as part of an ACTH stimulation test.", "Not dispensed to patients and not available through compounding pharmacies or telehealth." ], "faqs": [ { "q": "What is cosyntropin used for?", "a": "It is a diagnostic test agent. A single 250 mcg injection is given and cortisol is measured 30 and 60 minutes later; if the adrenal glands cannot raise cortisol above about 18 mcg per dL (500 nmol per L, assay dependent), adrenal insufficiency (adrenal glands that make too little cortisol) is likely. It is the confirmatory test recommended by the Endocrine Society for primary adrenal insufficiency (Addison disease, where the adrenal glands themselves fail).", "source_ids": [ "endo-guideline-2016", "fda-cortrosyn-label" ] }, { "q": "Is cosyntropin FDA approved?", "a": "Yes. Cortrosyn was approved in 1970 as a diagnostic agent for adrenocortical insufficiency and generic cosyntropin has been available for decades. It is not approved or used as a treatment; therapeutic ACTH products for conditions like infantile spasms are different drugs.", "source_ids": [ "fda-cortrosyn-label" ] }, { "q": "How accurate is the cosyntropin stimulation test?", "a": "Very good for primary adrenal insufficiency, where the adrenal glands themselves have failed. For secondary adrenal insufficiency (pituitary causes), a 2016 meta-analysis of 30 studies found the standard 250 mcg test misses about a third of cases (sensitivity around 64%) because partly atrophied adrenals can still respond to a large ACTH dose; the 1 mcg low dose test was more sensitive (about 92%). Cutoffs also depend on the cortisol assay used.", "source_ids": [ "ospina-2016", "endo-guideline-2016" ] }, { "q": "What are the side effects of cosyntropin?", "a": "Very few. Because it is a single diagnostic dose, the main risk is a rare allergic reaction, including anaphylaxis, which is more likely in people previously exposed to natural ACTH. Flushing, changes in heart rate, or blood pressure and rash have been reported rarely.", "source_ids": [ "fda-cortrosyn-label" ] }, { "q": "How is the cosyntropin stimulation test done, and what is the dose?", "a": "Blood is drawn for baseline cortisol, then cosyntropin is injected into a vein or muscle (0.25 mg for adults and children 2 to 17, 0.125 mg under age 2, per the label), and cortisol is drawn again exactly 30 and 60 minutes later. The label says to stop glucocorticoids and spironolactone on the test day and estrogen containing drugs 4 to 6 weeks before, because they distort cortisol readings. Guidelines note that dexamethasone does not cross react with cortisol assays if steroid cover is needed.", "source_ids": [ "fda-cortrosyn-label", "endo-guideline-2016" ] }, { "q": "How much does a cosyntropin test cost?", "a": "The drug itself is a generic vial costing in the low hundreds of USD, and the full test adds clinic time and two or three cortisol assays. It is normally billed to insurance as a diagnostic procedure rather than sold to the patient.", "source_ids": [ "fda-cortrosyn-label" ] }, { "q": "Is cosyntropin (tetracosactide) banned by WADA?", "a": "Yes. Corticotrophins and their releasing factors, with tetracosactide named as an example, are prohibited at all times under section S2 of the WADA Prohibited List because they stimulate cortisol release. An athlete who needs a diagnostic ACTH stimulation test should obtain a therapeutic use exemption or document the medical procedure with their anti-doping organization in advance.", "source_ids": [ "wada-list" ] }, { "q": "Cosyntropin vs ACTH gel: what is the difference?", "a": "Cosyntropin is the synthetic 24 amino acid fragment used once as a diagnostic test. Repository corticotropin gel is the full 39 amino acid natural hormone formulated for repeated therapeutic injection in conditions like infantile spasms and multiple sclerosis flares, at a very different cost and risk profile. They should not be confused, and cosyntropin is not a substitute for therapeutic ACTH.", "source_ids": [ "fda-cortrosyn-label", "husebye-2021" ] } ], "studies": [ { "pmid": "26649617", "title": "ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis", "year": 2016, "design": "Systematic review and meta-analysis of diagnostic accuracy studies (30 studies)", "population": "Patients evaluated for primary or secondary adrenal insufficiency with standard dose (250 mcg) or low dose (1 mcg) cosyntropin tests", "outcome": "Standard dose test sensitivity about 64% and low dose about 92% for secondary adrenal insufficiency with similar specificity; both tests perform well in primary adrenal insufficiency", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26649617/" }, { "pmid": "26760044", "title": "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline", "year": 2016, "design": "Clinical practice guideline based on systematic evidence review", "population": "Patients with suspected or confirmed primary adrenal insufficiency", "outcome": "Recommends the 250 mcg cosyntropin test as the confirmatory test, with peak cortisol under 500 nmol per L (18 mcg per dL) at 30 or 60 minutes indicating adrenal insufficiency, assay dependent", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26760044/" } ], "sources": [ { "id": "ospina-2016", "type": "pubmed", "title": "Ospina NS et al. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26649617/", "pmid": "26649617", "year": 2016 }, { "id": "endo-guideline-2016", "type": "pubmed", "title": "Bornstein SR et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26760044/", "pmid": "26760044", "year": 2016 }, { "id": "husebye-2021", "type": "pubmed", "title": "Husebye ES, Pearce SH, Krone NP, Kampe O. Adrenal insufficiency. Lancet 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33484633/", "pmid": "33484633", "year": 2021 }, { "id": "fda-cortrosyn-label", "type": "fda", "title": "FDA prescribing information for Cortrosyn (cosyntropin) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=746856e9-3930-4f6a-b8e6-a03845d6dd0b", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics (corticotrophins and their releasing factors)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "tesamorelin", "sermorelin", "gonadorelin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Cosyntropin (Cortrosyn): uses, side effects, and dosing", "description": "Cortrosyn is cosyntropin, the drug used in the ACTH stimulation test for adrenal insufficiency. How the test works, the FDA label dose, and side effects.", "h1": "Cosyntropin (Cortrosyn) stimulation test", "headings": { "dosing": "Cosyntropin stimulation test: dose on the FDA label" } } }, { "slug": "ganirelix", "name": "Ganirelix", "aliases": [ "Ganirelix Acetate Injection", "Orgalutran", "Antagon", "Fyremadel", "Org 37462" ], "class": "Gonadotropin releasing hormone (GnRH) antagonist, synthetic decapeptide", "one_liner": "FDA approved daily IVF injection that blocks early ovulation; live birth rates equal to older protocols with about 40% less ovarian overstimulation.", "summary": "Ganirelix is an FDA approved GnRH antagonist (approved 1999), a drug that blocks the brain hormone signal that triggers ovulation, given as a 250 mcg daily injection under the skin during ovarian stimulation for IVF to prevent a premature LH surge (the hormone spike that releases eggs). A Cochrane review (a rigorous pooled analysis) of 73 randomized trials in 12,212 women found no difference in live birth rate between antagonist and the older long agonist protocols (odds ratio 1.02, essentially equal) and a roughly 40% lower rate of ovarian hyperstimulation syndrome, a dangerous overreaction of the ovaries, with antagonists. It is a routine fertility clinic drug, not a research peptide.", "mechanism": "Ganirelix competitively blocks GnRH receptors on pituitary gonadotroph cells. Within hours it suppresses release of LH and, to a lesser extent, FSH, without the initial flare of hormone release that GnRH agonists cause. Starting it midway through ovarian stimulation prevents the premature LH surge that would otherwise trigger ovulation before egg retrieval, and suppression reverses within about 2 days of stopping.", "evidence_grade": "human_rct", "evidence_summary": "Multiple randomized trials and a large Cochrane meta-analysis. A dose finding trial (n = 333) established 0.25 mg daily as the optimal dose. Randomized comparisons against long agonist protocols (triptorelin, n = 730; leuprolide, n = 313) showed shorter stimulation, fewer gonadotropin doses, and similar although numerically slightly lower ongoing pregnancy rates. Cochrane 2016 (73 RCTs, 12,212 women): live birth odds ratio 1.02 (95% CI 0.85 to 1.23) and ovarian hyperstimulation syndrome odds ratio 0.61 (95% CI 0.51 to 0.72) for antagonists versus agonists.", "human_evidence": "Ganirelix Dose-finding Study Group 1998 (n = 333, six doses from 0.0625 to 2 mg daily): 0.25 mg gave the highest implantation and ongoing pregnancy rates, with higher doses suppressing LH too deeply. European and Middle East Orgalutran Study Group 2001 (n = 730): ongoing pregnancy rate 20.3% with ganirelix versus 25.7% with a long triptorelin protocol, with 5 fewer days of gonadotropins and no premature LH surges in either arm at meaningful rates. Fluker 2001 (n = 313, North America): ganirelix versus leuprolide, comparable safety and pregnancy outcomes with a shorter treatment course. Cochrane 2016 pooled across all GnRH antagonists: no difference in live birth, 39% lower odds of OHSS.", "animal_evidence": "Preclinical studies in rats and monkeys established rapid, reversible suppression of LH and FSH and set the dose range. Reproductive toxicology showed fetal resorption when given during early pregnancy, which underlies the pregnancy contraindication.", "conditions": [], "literature_dosing": "FDA label (ganirelix acetate injection, DailyMed): after FSH therapy starts on cycle day 2 or 3, 250 mcg is injected subcutaneously once daily during the mid to late portion of the follicular phase and continued daily until the day of hCG administration. The label says hCG should be withheld if the ovaries are abnormally enlarged on the last day of FSH therapy, to lower the chance of ovarian hyperstimulation syndrome. The dose finding trial tested 0.0625 to 2 mg daily and selected 0.25 mg.", "routes": [ "Subcutaneous injection once daily (prefilled syringe)" ], "side_effects": [ "Injection site reactions (redness, bruising, itching)", "Headache", "Abdominal pain and nausea (often related to ovarian stimulation rather than ganirelix itself)", "Vaginal bleeding", "Ovarian hyperstimulation syndrome, at a lower rate than with agonist protocols", "Rare hypersensitivity reactions" ], "interactions": [ "No formal drug interaction studies; ganirelix is a peptide and is not expected to interact through cytochrome P450 enzymes", "Used by design with FSH, hMG, and hCG in stimulation protocols" ], "contraindications": [ "Pregnancy or suspected pregnancy (fetal loss in animal studies)", "Known hypersensitivity to ganirelix, GnRH, or GnRH analogs", "Latex allergy for some prefilled syringe presentations (needle shield)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (originally Antagon, approved July 1999; now sold as Ganirelix Acetate Injection and generic and branded equivalents). Commercially available in prefilled syringes, so it is not eligible for routine compounding and is not on any 503A bulks list. Not a research chemical.", "typical_cost": "Roughly 100 to 200 USD per 250 mcg prefilled syringe at US pharmacies, and a typical IVF cycle uses 4 to 6 syringes. Fertility benefits vary widely; many patients pay cash as part of an IVF medication package. Prices verified on the last verified date.", "access_path": [ "Prescription from a fertility specialist as part of an IVF or egg freezing protocol, filled at a specialty or fertility pharmacy.", "Not available through compounding pharmacies or telehealth peptide clinics." ], "faqs": [ { "q": "Is ganirelix FDA approved, and what is it used for?", "a": "Yes, since 1999, sold today as ganirelix acetate injection and Fyremadel along with several generics. The label has one use: inhibiting premature LH surges (the hormone spike that triggers ovulation) in women undergoing controlled ovarian hyperstimulation for assisted reproduction. It blocks pituitary GnRH receptors, the switch the brain uses to release LH, so that ovulation can be triggered on schedule with an hCG shot.", "source_ids": [ "fda-ganirelix-label", "fda-fyremadel-label" ] }, { "q": "What does ganirelix do in IVF?", "a": "It blocks the pituitary from releasing the LH surge that would trigger ovulation early, so eggs are not lost before retrieval. It is started around day 5 or 6 of stimulation and continued daily until the trigger shot. Unlike GnRH agonists such as leuprolide, it works within hours, needs no lead in period, and does not cause an initial hormone flare.", "source_ids": [ "fda-ganirelix-label", "orgalutran-2001" ] }, { "q": "Does ganirelix lower IVF success rates?", "a": "Not by the best available evidence. Early trials found numerically lower ongoing pregnancy rates with ganirelix than with long agonist protocols (for example 20.3% versus 25.7% in the 730 woman European trial), which was not statistically significant. The 2016 Cochrane review of 73 randomized trials in 12,212 women found no difference in live birth (odds ratio 1.02, 95% CI 0.85 to 1.23) and 39% lower odds of ovarian hyperstimulation syndrome with antagonist protocols.", "source_ids": [ "cochrane-2016", "orgalutran-2001" ] }, { "q": "What are the side effects of ganirelix?", "a": "Mostly minor: injection site redness or bruising, headache, and nausea. Abdominal pain and bloating in trials were largely due to the ovarian stimulation itself. Ovarian hyperstimulation syndrome can still occur but is less frequent than with agonist protocols. Ganirelix must not be given if a woman is already pregnant.", "source_ids": [ "fda-ganirelix-label", "cochrane-2016" ] }, { "q": "What is the ganirelix dose on the FDA label?", "a": "250 mcg under the skin once a day from a prefilled syringe during the mid to late follicular phase, after FSH has been started on cycle day 2 or 3, continuing every day until the day of the hCG trigger. Missing a dose risks a premature LH surge.", "source_ids": [ "fda-ganirelix-label", "ganirelix-dose-1998" ] }, { "q": "How much does ganirelix cost?", "a": "Roughly 100 to 200 USD per syringe in the United States, and most cycles need 4 to 6 syringes, so 400 to 1,200 USD per cycle. Coverage depends on whether a plan includes fertility medication benefits; many patients pay out of pocket as part of an IVF medication bundle.", "source_ids": [ "fda-ganirelix-label" ] }, { "q": "Is ganirelix banned by WADA?", "a": "No. GnRH antagonists are not named on the WADA Prohibited List; the list prohibits GnRH agonists and LH releasing agents in males because they can raise testosterone. Ganirelix lowers gonadotropins and has no performance enhancing use. Athletes in fertility treatment should still confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "q": "Ganirelix vs cetrorelix: which is better?", "a": "They are interchangeable GnRH antagonists with the same 0.25 mg daily dosing and the same role in IVF. No large head to head trial shows a difference in pregnancy rates, and the Cochrane review pools them. Clinics choose based on pharmacy availability, price, and syringe versus vial presentation.", "source_ids": [ "cochrane-2016" ] } ], "studies": [ { "pmid": "9853849", "title": "A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone", "year": 1998, "design": "Randomized, double blind, dose finding trial (six dose groups)", "n": 333, "population": "Women undergoing ovarian stimulation for IVF", "outcome": "0.25 mg daily produced the highest implantation and ongoing pregnancy rates; higher doses over suppressed LH and estradiol", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/9853849/" }, { "pmid": "11278211", "title": "Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation", "year": 2001, "design": "Randomized, open label, multicenter trial, 2:1 allocation", "n": 730, "population": "Women undergoing ovarian stimulation for IVF or ICSI in Europe and the Middle East", "outcome": "Ongoing pregnancy rate 20.3% with ganirelix versus 25.7% with triptorelin (not statistically significant); shorter stimulation and fewer FSH doses with ganirelix", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/11278211/" }, { "pmid": "11163814", "title": "Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation", "year": 2001, "design": "Randomized, open label, multicenter trial", "n": 313, "population": "Women undergoing controlled ovarian hyperstimulation for IVF in North America", "outcome": "Comparable ongoing pregnancy rates and safety with ganirelix versus a long leuprolide protocol, with shorter treatment duration", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/11163814/" }, { "pmid": "27126581", "title": "Gonadotrophin-releasing hormone antagonists for assisted reproductive technology", "year": 2016, "design": "Cochrane systematic review and meta-analysis of 73 randomized trials", "n": 12212, "population": "Women undergoing assisted reproduction with GnRH antagonist versus GnRH agonist protocols", "outcome": "Live birth odds ratio 1.02 (95% CI 0.85 to 1.23); ovarian hyperstimulation syndrome odds ratio 0.61 (95% CI 0.51 to 0.72) favoring antagonists", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27126581/" } ], "sources": [ { "id": "ganirelix-dose-1998", "type": "pubmed", "title": "Ganirelix Dose-finding Study Group. A double-blind, randomized, dose-finding study of ganirelix (Org 37462) to prevent premature LH surges in women undergoing ovarian stimulation. Hum Reprod 1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9853849/", "pmid": "9853849", "year": 1998 }, { "id": "orgalutran-2001", "type": "pubmed", "title": "European and Middle East Orgalutran Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin. Hum Reprod 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11278211/", "pmid": "11278211", "year": 2001 }, { "id": "fluker-2001", "type": "pubmed", "title": "Fluker M et al. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001", "url": "https://pubmed.ncbi.nlm.nih.gov/11163814/", "pmid": "11163814", "year": 2001 }, { "id": "cochrane-2016", "type": "pubmed", "title": "Al-Inany HG et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27126581/", "pmid": "27126581", "year": 2016 }, { "id": "fda-ganirelix-label", "type": "fda", "title": "FDA prescribing information for ganirelix acetate injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32fb74ff-993a-49fe-8943-e029372b863e", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "fda-fyremadel-label", "type": "fda", "title": "FDA prescribing information for Fyremadel (ganirelix acetate) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f0908b5-3551-47fd-95f7-3669b0dff7f1", "year": 2025 } ], "related": [ "cetrorelix", "leuprolide", "triptorelin", "degarelix" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Ganirelix (Fyremadel): uses, side effects, and dosing", "description": "Ganirelix is a GnRH antagonist injection that blocks a premature LH surge during IVF stimulation. FDA label use, the 250 mcg daily dose, side effects, cost.", "h1": "Ganirelix (Fyremadel)" } }, { "slug": "cetrorelix", "name": "Cetrorelix", "aliases": [ "Cetrotide", "cetrorelix acetate", "SB-75", "NS-75A" ], "class": "Gonadotropin releasing hormone (GnRH) antagonist, synthetic decapeptide", "one_liner": "FDA approved IVF injection (2000) that prevents early ovulation; pregnancy rates similar to older protocols with fewer cases of ovarian overstimulation.", "summary": "Cetrorelix is an FDA approved GnRH antagonist (Cetrotide, approved August 2000), a drug that blocks the brain hormone signal that triggers ovulation, given as a 0.25 mg daily injection under the skin during ovarian stimulation to stop a premature LH surge (the hormone spike that releases eggs) before egg retrieval. In the pivotal European phase 3 trial it produced clinical pregnancy rates comparable to the older long protocol using the agonist buserelin (22.3% versus 25.8% per attempt) with far fewer cases of moderate to severe ovarian hyperstimulation syndrome, a dangerous overreaction of the ovaries (1.1% versus 6.5%). A Cochrane review (a rigorous pooled analysis) of 73 trials confirms antagonists and agonists give the same live birth rate. It is a routine fertility clinic drug, not a research peptide.", "mechanism": "Cetrorelix competitively occupies GnRH receptors on pituitary gonadotrophs and blocks the pulsatile GnRH signal, so LH and FSH secretion falls within hours without the initial flare seen with GnRH agonists. During ovarian stimulation this prevents the estradiol driven LH surge that would trigger ovulation prematurely. Suppression is dose dependent and reverses within days after the last injection.", "evidence_grade": "human_rct", "evidence_summary": "Randomized trials in IVF support both the daily 0.25 mg regimen and a single 3 mg regimen. The pivotal European phase 3 trial versus buserelin showed comparable pregnancy rates with fewer gonadotropin ampoules, shorter stimulation, and markedly less ovarian hyperstimulation syndrome. A single dose trial (n = 115) versus triptorelin showed similar outcomes. Cochrane 2016 (73 RCTs, 12,212 women, all GnRH antagonists): live birth odds ratio 1.02 and ovarian hyperstimulation syndrome odds ratio 0.61 versus agonist protocols.", "human_evidence": "Albano 2000 (randomized phase 3, cetrorelix 0.25 mg daily versus long buserelin protocol): clinical pregnancy per attempt 22.3% versus 25.8%, ovarian hyperstimulation syndrome grade II or III in 1.1% versus 6.5%, and fewer hMG ampoules and stimulation days with cetrorelix. Olivennes 2000 (n = 115, single 3 mg cetrorelix dose versus triptorelin long protocol): no premature LH surges in the cetrorelix group and comparable pregnancy rates with shorter treatment. Cochrane 2016 across antagonists: no difference in live birth (OR 1.02, 95% CI 0.85 to 1.23) and lower OHSS (OR 0.61, 95% CI 0.51 to 0.72).", "animal_evidence": "Preclinical studies in rodents and primates established rapid reversible gonadotropin suppression, and cetrorelix was also studied in animal models of hormone dependent tumors and benign prostatic hyperplasia before development focused on fertility. Reproductive toxicology showed pregnancy loss when given during early gestation.", "conditions": [], "literature_dosing": "FDA label (Cetrotide 0.25 mg, DailyMed): after gonadotropin stimulation starts on cycle day 2 or 3, 0.25 mg is injected subcutaneously once daily during the early to mid follicular phase, beginning on stimulation day 5 (morning or evening) or day 6 (morning) and continuing daily until the day of hCG administration. The label says hCG should not be given if the ovaries respond excessively, to lower the chance of ovarian hyperstimulation syndrome. A single 3 mg regimen was studied in trials but is not on the current US label.", "routes": [ "Subcutaneous injection once daily (0.25 mg vial with diluent syringe)", "Single 3 mg subcutaneous injection (studied regimen, not on the US label)" ], "side_effects": [ "Injection site reactions (redness, itching, swelling), usually mild and transient", "Nausea and headache", "Ovarian hyperstimulation syndrome, at a lower rate than with agonist protocols (1.1% versus 6.5% grade II or III in the pivotal trial)", "Rare hypersensitivity reactions including anaphylactoid reactions after months of use in non-fertility studies" ], "interactions": [ "No formal drug interaction studies; cetrorelix is a peptide and is not metabolized by cytochrome P450 enzymes", "Used by design with FSH, hMG, and hCG in stimulation protocols" ], "contraindications": [ "Pregnancy or breastfeeding", "Known hypersensitivity to cetrorelix, extrinsic peptide hormones, mannitol, or GnRH analogs", "Severe renal impairment (per label)" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved prescription drug (Cetrotide, approved August 11, 2000) to inhibit premature LH surges in women undergoing controlled ovarian stimulation. Commercially available as a 0.25 mg kit, so it is not eligible for routine compounding and is not on any 503A bulks list. Not a research chemical.", "typical_cost": "Roughly 100 to 250 USD per 0.25 mg dose at US pharmacies, with a typical cycle using 4 to 6 doses. Coverage depends on fertility medication benefits; many patients pay cash as part of an IVF medication package. Prices verified on the last verified date.", "access_path": [ "Prescription from a fertility specialist as part of an IVF or egg freezing protocol, filled at a specialty or fertility pharmacy.", "Not available through compounding pharmacies or telehealth peptide clinics." ], "faqs": [ { "q": "Is cetrorelix (Cetrotide) FDA approved, and what is it used for?", "a": "Yes, since 2000. The Cetrotide label has one use: inhibiting premature LH surges (the hormone spike that triggers ovulation) in women undergoing controlled ovarian stimulation, as in IVF and other assisted reproduction cycles. Blocking pituitary GnRH receptors, the switch the brain uses to release LH, keeps LH from rising before the eggs are ready, so ovulation can be timed with an hCG trigger shot. It is prescription only, and generic cetrorelix kits are also on DailyMed.", "source_ids": [ "fda-cetrotide-label" ] }, { "q": "What does cetrorelix do during IVF?", "a": "It prevents the LH surge that would make the ovaries release eggs before the retrieval procedure. It is started midway through stimulation (around day 5 to 7) and continued daily until the trigger injection. Because it works within hours, patients avoid the two to three weeks of pituitary down regulation needed with agonist protocols.", "source_ids": [ "fda-cetrotide-label", "albano-2000" ] }, { "q": "Does cetrorelix reduce IVF success?", "a": "The best evidence says no. In the pivotal trial, clinical pregnancy per attempt was 22.3% with cetrorelix versus 25.8% with a long buserelin protocol, a difference that was not statistically significant, while severe ovarian hyperstimulation fell from 6.5% to 1.1%. The 2016 Cochrane review of 73 randomized trials found identical live birth rates for antagonist and agonist protocols (odds ratio 1.02).", "source_ids": [ "albano-2000", "cochrane-2016" ] }, { "q": "What are the side effects of cetrorelix?", "a": "Mainly injection site redness, itching, or swelling, plus nausea and headache. Ovarian hyperstimulation syndrome can still occur but is less common than with agonist protocols. Rare allergic reactions have been reported. It must not be used during pregnancy.", "source_ids": [ "fda-cetrotide-label", "albano-2000" ] }, { "q": "What is the cetrorelix (Cetrotide) dose on the FDA label?", "a": "0.25 mg under the skin once a day, starting on stimulation day 5 (morning or evening) or day 6 (morning) and continuing until the day of the hCG trigger. The label allows patients to self inject after instruction from their doctor. The 3 mg single dose regimen used in some countries is not on the US label.", "source_ids": [ "fda-cetrotide-label" ] }, { "q": "How much does cetrorelix cost?", "a": "About 100 to 250 USD per 0.25 mg dose in the United States, or roughly 400 to 1,500 USD for a cycle of 4 to 6 doses. Whether insurance covers it depends on fertility benefits; a large share of patients pay out of pocket as part of their IVF medication bundle.", "source_ids": [ "fda-cetrotide-label" ] }, { "q": "Is cetrorelix banned by WADA?", "a": "No. GnRH antagonists are not named on the WADA Prohibited List, which prohibits GnRH agonists and other LH releasing agents only in males. Cetrorelix suppresses sex hormones rather than raising them and has no performance enhancing use.", "source_ids": [ "wada-list" ] }, { "q": "Cetrorelix vs ganirelix: is there a difference?", "a": "Functionally no. Both are GnRH antagonists dosed at 0.25 mg daily with the same role and similar side effects, and the Cochrane review treats them together. Ganirelix comes as a prefilled syringe while cetrorelix is reconstituted from a vial; price and pharmacy stock usually decide which a clinic uses.", "source_ids": [ "cochrane-2016" ] } ], "studies": [ { "pmid": "10686191", "title": "Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin", "year": 2000, "design": "Randomized, open label, multicenter phase 3 trial", "population": "Women undergoing ovarian stimulation with hMG for IVF or ICSI in Europe", "outcome": "Clinical pregnancy per attempt 22.3% with cetrorelix versus 25.8% with buserelin (not significant); OHSS grade II or III 1.1% versus 6.5%; fewer hMG ampoules and stimulation days", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/10686191/" }, { "pmid": "10685535", "title": "Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin)", "year": 2000, "design": "Randomized, controlled trial", "n": 115, "population": "Women undergoing IVF with embryo transfer", "outcome": "Single 3 mg cetrorelix dose prevented premature LH surges with comparable pregnancy rates and shorter, lower dose stimulation than triptorelin depot", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/10685535/" }, { "pmid": "27126581", "title": "Gonadotrophin-releasing hormone antagonists for assisted reproductive technology", "year": 2016, "design": "Cochrane systematic review and meta-analysis of 73 randomized trials", "n": 12212, "population": "Women undergoing assisted reproduction with GnRH antagonist versus GnRH agonist protocols", "outcome": "Live birth odds ratio 1.02 (95% CI 0.85 to 1.23); ovarian hyperstimulation syndrome odds ratio 0.61 (95% CI 0.51 to 0.72) favoring antagonists", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27126581/" } ], "sources": [ { "id": "albano-2000", "type": "pubmed", "title": "Albano C et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the LHRH antagonist cetrorelix and the LHRH agonist buserelin. Hum Reprod 2000", "url": "https://pubmed.ncbi.nlm.nih.gov/10686191/", "pmid": "10686191", "year": 2000 }, { "id": "olivennes-2000", "type": "pubmed", "title": "Olivennes F et al. Prospective, randomized, controlled study of IVF-embryo transfer with a single dose of cetrorelix or a depot formula of triptorelin. Fertil Steril 2000", "url": "https://pubmed.ncbi.nlm.nih.gov/10685535/", "pmid": "10685535", "year": 2000 }, { "id": "cochrane-2016", "type": "pubmed", "title": "Al-Inany HG et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27126581/", "pmid": "27126581", "year": 2016 }, { "id": "fda-cetrotide-label", "type": "fda", "title": "FDA prescribing information for Cetrotide (cetrorelix acetate for injection) 0.25 mg, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aca7768e-28a7-4027-b1d8-e66247665f79", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "ganirelix", "leuprolide", "degarelix", "triptorelin" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Cetrorelix (Cetrotide): uses, side effects, and dosing", "description": "Cetrotide is cetrorelix, a GnRH antagonist injection that prevents a premature LH surge during IVF stimulation. FDA label use, dose, side effects, and cost.", "h1": "Cetrorelix (Cetrotide)" } }, { "slug": "secretin", "name": "Secretin", "aliases": [ "ChiRhoStim", "human secretin", "synthetic human secretin", "porcine secretin", "SecreFlo" ], "class": "Gastrointestinal hormone (27 amino acid peptide of the secretin/glucagon family), used as a diagnostic agent", "one_liner": "FDA approved diagnostic peptide for pancreatic function and gastrinoma testing; randomized trials found no benefit in autism.", "summary": "Secretin is a natural gut hormone that is FDA approved in synthetic form (ChiRhoStim, human secretin, approved 2004) as a diagnostic agent: it stimulates pancreatic bicarbonate secretion to test exocrine pancreatic function, provokes gastrin release to diagnose gastrinoma (Zollinger-Ellison syndrome), and helps locate the pancreatic duct during ERCP. It became famous in the late 1990s as a proposed autism treatment, but a randomized trial in 60 children and a Cochrane review of more than a dozen trials found no benefit. It is used only in hospitals and endoscopy units, not as a therapy.", "mechanism": "Secretin is released by duodenal S cells when acidic chyme enters the small intestine. It binds secretin receptors on pancreatic duct cells, raising cyclic AMP and driving secretion of bicarbonate rich fluid that neutralizes gastric acid. It also inhibits gastric acid secretion and gastrin release in normal tissue, but paradoxically stimulates gastrin release from gastrinoma cells, which is the basis of the secretin stimulation test for Zollinger-Ellison syndrome.", "evidence_grade": "human_rct", "evidence_summary": "For its approved diagnostic uses, the evidence base is decades of physiology and diagnostic accuracy studies: secretin stimulated pancreatic fluid analysis remains a reference standard for exocrine pancreatic function, and a gastrin rise of 120 pg per mL or more after secretin is the accepted criterion for gastrinoma. For autism, where it was widely promoted, a double blind randomized trial (n = 60) found no benefit over placebo and a Cochrane review of randomized trials in about 900 children found no evidence of effect. The evidence grade reflects those randomized trials, which show it does not work for autism, and observational diagnostic data for approved uses.", "human_evidence": "Sandler 1999 (randomized, double blind, placebo controlled, n = 60): a single intravenous dose of synthetic human secretin produced no improvement in autism symptom scores versus placebo at 4 weeks; parents could not distinguish active drug from placebo. Williams 2012 Cochrane review: across randomized trials of single and repeated secretin doses in children with autism spectrum disorder, no significant effect on core symptoms was found and the authors concluded further trials were not justified. Stevens 2008 (crossover, endoscopic versus Dreiling tube collection): secretin stimulated endoscopic pancreatic function testing gave comparable bicarbonate results to the traditional tube method in patients evaluated for chronic pancreatitis.", "animal_evidence": "Secretin was the first hormone ever identified (Bayliss and Starling, 1902, in dogs). Animal physiology established its release from the duodenum, its stimulation of pancreatic bicarbonate secretion, and its receptor pharmacology. Some rodent studies report central nervous system effects, which fueled the autism hypothesis but did not translate to human benefit.", "conditions": [], "literature_dosing": "FDA label (ChiRhoStim, DailyMed; diagnostic use only, by intravenous injection over 1 minute): 0.2 mcg/kg to stimulate pancreatic secretions, including bicarbonate, to aid in diagnosing exocrine pancreas dysfunction; 0.4 mcg/kg to stimulate gastrin secretion to aid in diagnosing gastrinoma; 0.2 mcg/kg to stimulate pancreatic secretions to help identify the ampulla of Vater and accessory papilla during ERCP. There is no labeled therapeutic dose.", "routes": [ "Intravenous bolus (diagnostic use only)" ], "side_effects": [ "Flushing, nausea, vomiting, and mild abdominal discomfort during infusion", "Transient changes in heart rate or blood pressure", "Rare hypersensitivity reactions; a test dose is sometimes used in patients with prior exposure", "In the autism trials, adverse effects were mild and similar to placebo" ], "interactions": [ "Anticholinergic drugs reduce the pancreatic response to secretin and can cause a false result; the label advises stopping them before testing", "Proton pump inhibitors and H2 blockers raise baseline gastrin and complicate interpretation of the gastrinoma test; they are usually held before testing when safe to do so" ], "contraindications": [ "Acute pancreatitis (test should be delayed until the episode resolves)", "Known hypersensitivity to secretin", "Not approved or effective as a treatment for any condition, including autism" ], "wada_status": "not_prohibited", "fda_status": "fda_approved", "compounding_status": "FDA approved diagnostic drug: synthetic porcine secretin (SecreFlo) was approved in 2002 and synthetic human secretin (ChiRhoStim) in 2004; the human product is the one currently marketed. It is a hospital and endoscopy unit agent with no therapeutic indication, so there is no compounding or telehealth market and it is not on any 503A bulks list. Some research chemical sellers list secretin, but there is no evidence based human use outside diagnostic testing.", "typical_cost": "Unknown at the patient level; single use diagnostic vials are administered in hospital and billed as part of the endoscopy or laboratory procedure. The vial price is high enough that testing is reserved for defined indications.", "access_path": [ "Administered intravenously by a gastroenterologist or endoscopist in a hospital or endoscopy unit for pancreatic function testing, gastrinoma testing, or ERCP.", "Not dispensed to patients and not available through compounding pharmacies or telehealth." ], "faqs": [ { "q": "What is secretin used for?", "a": "Three FDA approved diagnostic uses: stimulating pancreatic fluid so its bicarbonate content can be measured to assess exocrine pancreatic function (for example in chronic pancreatitis), provoking gastrin release to diagnose gastrinoma in Zollinger-Ellison syndrome, and making the pancreatic duct opening easier to find during ERCP. It is not a treatment for anything.", "source_ids": [ "fda-chirhostim-label", "stevens-2008" ] }, { "q": "Is secretin FDA approved?", "a": "Yes, as a diagnostic agent. Synthetic porcine secretin was approved in 2002 and synthetic human secretin (ChiRhoStim) in 2004, replacing the biologically extracted product that had been used for decades. Approval covers pancreatic function testing, gastrinoma testing, and aid to ERCP cannulation only.", "source_ids": [ "fda-chirhostim-label" ] }, { "q": "Does secretin help autism?", "a": "No. After anecdotal reports in 1998, a double blind randomized trial in 60 children found that a single intravenous dose of synthetic human secretin was no better than placebo on autism symptom scores, and parents could not tell which their child received. A Cochrane review of randomized trials in about 900 children, including repeated dose studies, found no effect on core symptoms and concluded that further trials were not warranted.", "source_ids": [ "sandler-1999", "cochrane-autism-2012" ] }, { "q": "What are the side effects of secretin?", "a": "Usually minor and brief because it is a single intravenous dose: flushing, nausea, mild abdominal discomfort, and transient changes in heart rate or blood pressure. Allergic reactions are rare. It should not be given during acute pancreatitis. In the autism trials, side effects were no different from placebo.", "source_ids": [ "fda-chirhostim-label", "sandler-1999" ] }, { "q": "How is the secretin stimulation test done?", "a": "For gastrinoma, a baseline gastrin level is drawn, 0.4 mcg per kg of secretin is injected intravenously over 1 minute, and gastrin is measured at 1, 2, 5, 10, and 30 minutes; a rise of 120 pg per mL or more above baseline supports gastrinoma. For pancreatic function, 0.2 mcg per kg is given and duodenal fluid is collected by tube or endoscope over about an hour to measure bicarbonate concentration.", "source_ids": [ "fda-chirhostim-label", "stevens-2008" ] }, { "q": "How much does secretin cost?", "a": "Patients rarely see a direct price because it is given in hospital or endoscopy units and billed with the procedure. The synthetic human product is expensive per vial, which is why the test is reserved for defined indications rather than used as a screening tool. No cash pay or outpatient channel exists.", "source_ids": [ "fda-chirhostim-label" ] }, { "q": "Is secretin banned by WADA?", "a": "No. Secretin is not on the WADA Prohibited List. It is a digestive hormone with no effect on performance and is used only as a single dose diagnostic agent.", "source_ids": [ "wada-list" ] } ], "studies": [ { "pmid": "10588965", "title": "Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder", "year": 1999, "design": "Randomized, double blind, placebo controlled trial, 4 week follow up", "n": 60, "population": "Children aged 3 to 14 with autism or pervasive developmental disorder", "outcome": "No difference from placebo on the Autism Behavior Checklist or other symptom measures; parents could not identify treatment assignment", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/10588965/" }, { "pmid": "22513913", "title": "Intravenous secretin for autism spectrum disorders (ASD)", "year": 2012, "design": "Cochrane systematic review of randomized controlled trials", "population": "Children with autism spectrum disorder given single or repeated intravenous secretin", "outcome": "No evidence that secretin improves core autism symptoms; authors concluded further trials are not justified", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/22513913/" }, { "pmid": "18294508", "title": "A prospective crossover study comparing secretin-stimulated endoscopic and Dreiling tube pancreatic function testing in patients evaluated for chronic pancreatitis", "year": 2008, "design": "Prospective crossover diagnostic study", "population": "Patients evaluated for chronic pancreatitis", "outcome": "Secretin stimulated endoscopic collection gave peak bicarbonate results comparable to the traditional Dreiling tube method", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/18294508/" } ], "sources": [ { "id": "sandler-1999", "type": "pubmed", "title": "Sandler AD et al. Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. N Engl J Med 1999", "url": "https://pubmed.ncbi.nlm.nih.gov/10588965/", "pmid": "10588965", "year": 1999 }, { "id": "cochrane-autism-2012", "type": "pubmed", "title": "Williams K et al. Intravenous secretin for autism spectrum disorders (ASD). Cochrane Database Syst Rev 2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22513913/", "pmid": "22513913", "year": 2012 }, { "id": "stevens-2008", "type": "pubmed", "title": "Stevens T et al. A prospective crossover study comparing secretin-stimulated endoscopic and Dreiling tube pancreatic function testing in patients evaluated for chronic pancreatitis. Gastrointest Endosc 2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18294508/", "pmid": "18294508", "year": 2008 }, { "id": "fda-chirhostim-label", "type": "fda", "title": "FDA prescribing information for ChiRhoStim (human secretin) for injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4dfe70f-0a86-4488-9ba1-dcd8f86cbfcd", "year": 2025 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "related": [ "vip", "glucagon", "octreotide" ], "cluster": "other", "last_verified": "2026-09-23", "review_status": "draft", "version": 3, "seo": { "title": "Secretin (ChiRhoStim): uses, side effects, and dosing", "description": "ChiRhoStim is human secretin, a diagnostic injection for pancreatic function testing, gastrinoma, and ERCP. FDA label uses, test doses, and side effects.", "h1": "Secretin (ChiRhoStim)" } } ], "meta": { "dataset": "peptides", "generated_at": "2026-09-28T02:14:37.172Z", "data_as_of": "2026-09-27", "records": 82, "license": "CC BY 4.0, attribution required: PeptideAgent (https://peptideagent.ai)", "license_url": "https://creativecommons.org/licenses/by/4.0/", "attribution": "Data from PeptideAgent (https://peptideagent.ai), licensed under CC BY 4.0.", "version": "1", "source": "https://peptideagent.ai/data" } }