{ "data": [ { "slug": "aod-9604-vs-5-amino-1mq", "a": "aod-9604", "b": "5-amino-1mq", "title": "AOD-9604 vs 5-Amino-1MQ", "summary": "Neither is a sound fat loss option: both have only mouse evidence, neither is FDA approved, neither has a lawful compounding basis, and both are prohibited in sport. AOD-9604, a growth hormone fragment, has actually been tested in human obesity trials that never produced a published positive result, while 5-Amino-1MQ, an oral NNMT inhibitor and not a peptide, has never been tested in people at all. If fat loss is the goal, FDA approved GLP-1 medicines have the evidence these two lack.", "verdict": { "winner": "depends", "rationale": "There is no winner on evidence or regulation. Both are graded animal only, and both lack any lawful US access path: AOD-9604's compounding nomination is listed by FDA as withdrawn, and 5-Amino-1MQ was never nominated and has no USP monograph. AOD-9604 is the more studied molecule, but the human trials that were run did not yield a published benefit and FDA cited serious adverse events of unclear causality; 5-Amino-1MQ has no human safety data of any kind. The honest answer is that neither should be chosen over an approved treatment.", "source_ids": [ "heffernan-2001-endo", "neelakantan-2018", "fda-category-2", "fda-503a-bulks" ] }, "dimensions": [ { "name": "What it is", "a": "A 16 amino acid fragment of human growth hormone (residues 177 to 191 with an added tyrosine).", "b": "An oral small molecule (5-amino-1-methylquinolinium), not a peptide.", "source_ids": [ "ng-2000", "neelakantan-2018" ] }, { "name": "Mechanism", "a": "Proposed to stimulate fat breakdown and inhibit fat synthesis through beta-3 adrenergic pathways without raising IGF-1 or glucose.", "b": "Inhibits nicotinamide N-methyltransferase (NNMT), raising NAD+ and SAM in fat cells, reducing fat synthesis, and increasing energy expenditure in mice.", "source_ids": [ "ng-2000", "heffernan-2001-endo", "neelakantan-2018" ] }, { "name": "Animal evidence", "a": "Reduced weight gain and fat mass and increased fat oxidation in obese mice; effect lost in beta-3 receptor knockout mice.", "b": "In diet induced obese mice, 11 days of treatment reduced body weight, white fat mass, adipocyte size, and cholesterol; in aged mice it activated muscle stem cells and improved regeneration.", "source_ids": [ "heffernan-2001-endo", "heffernan-2001-ijo", "neelakantan-2018", "neelakantan-2019" ] }, { "name": "Human testing", "a": "Sponsor ran human obesity trials in the early 2000s; no indexed publication reports a weight loss benefit and the program was discontinued.", "b": "No human pharmacokinetic, safety, or efficacy study has been published.", "source_ids": [ "fda-category-2", "neelakantan-2018" ] }, { "name": "Safety signals", "a": "FDA cited serious adverse events of unclear causality and immunogenicity risk from aggregation and impurities.", "b": "No human safety data; long term effects of altering NAD+ and methylation balance are unknown.", "source_ids": [ "fda-category-2", "neelakantan-2019" ] }, { "name": "FDA and compounding status", "a": "Placed in 503A Category 2 in 2023; nomination now listed as withdrawn. Not on the bulks list, so no lawful compounding basis.", "b": "Never nominated, not in Category 2, not on the bulks list, and no USP monograph, so it meets none of the 503A bulk substance criteria.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Prohibited at all times under S2 as a growth hormone fragment.", "b": "Prohibited at all times under S0 as a non-approved substance.", "source_ids": [ "wada-list" ] }, { "name": "Route", "a": "Subcutaneous injection as sold; oral and injectable in mouse studies.", "b": "Oral capsule as sold; injection and oral gavage in mouse studies.", "source_ids": [ "heffernan-2001-endo", "neelakantan-2018" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which works better for fat loss, AOD-9604 or 5-Amino-1MQ?", "a": "Neither has shown fat loss in humans. Both reduced fat mass in obese mice. AOD-9604's human trials never produced a published positive result, and 5-Amino-1MQ has never been tested in people.", "source_ids": [ "heffernan-2001-endo", "neelakantan-2018" ] }, { "q": "Can a compounding pharmacy make either one?", "a": "Not lawfully. AOD-9604's nomination is listed by FDA as withdrawn and it is not on the 503A bulks list. 5-Amino-1MQ was never nominated and has no USP monograph. Capsules or vials sold by clinics or online are unapproved drugs.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Is 5-Amino-1MQ a peptide?", "a": "No. It is a small quinolinium molecule that inhibits the enzyme NNMT. It is often sold alongside peptides, but chemically it is unrelated.", "source_ids": [ "neelakantan-2018" ] }, { "q": "Are they banned in sport?", "a": "Yes. AOD-9604 is prohibited under WADA section S2 as a growth hormone fragment, and 5-Amino-1MQ is prohibited under S0 as a non-approved substance.", "source_ids": [ "wada-list" ] } ], "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": "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-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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 non-approved substances and section S2 growth hormone fragments)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "aod-9604-vs-semaglutide", "a": "aod-9604", "b": "semaglutide", "title": "AOD-9604 vs semaglutide", "summary": "Semaglutide is the clear choice for weight loss: it is FDA approved, produced 14.9% average weight loss versus 2.4% on placebo at 68 weeks in STEP 1, and reduced major cardiovascular events by 20% in SELECT. AOD-9604, a growth hormone fragment, reduced fat in obese mice, but its human obesity program was discontinued without a published positive result, and it has no lawful US access path. The only thing AOD-9604 has going for it is fewer gastrointestinal side effects, which reflects the absence of a demonstrated effect rather than an advantage.", "verdict": { "winner": "b", "rationale": "Semaglutide wins on every axis that matters: evidence grade (multiple large RCTs with weight and cardiovascular outcomes versus animal only), regulatory status (FDA approved as Wegovy, Ozempic, and Rybelsus versus a withdrawn compounding nomination with no bulks listing), and access (prescription at any pharmacy versus no lawful source). AOD-9604's sponsor ran human obesity trials that never produced an indexed positive result, and FDA's Category 2 review cited serious adverse events of unclear causality.", "source_ids": [ "step-1", "select", "fda-wegovy-label", "heffernan-2001-endo", "fda-category-2", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Animal only. Mouse studies from one group around 2000 to 2001; no indexed human trial reporting weight loss.", "b": "Human RCT. STEP 1 (1,961 adults), SUSTAIN-6 (3,297 adults with type 2 diabetes), and SELECT (17,604 adults) among many trials.", "source_ids": [ "ng-2000", "heffernan-2001-endo", "step-1", "sustain-6", "select" ] }, { "name": "Weight loss", "a": "Reduced weight gain and fat mass in obese mice, with the effect lost in beta-3 adrenergic receptor knockout mice. No published human weight loss result.", "b": "14.9% mean weight loss versus 2.4% with placebo at 68 weeks (STEP 1); 86.4% lost at least 5% of body weight.", "source_ids": [ "heffernan-2001-endo", "heffernan-2001-ijo", "step-1" ] }, { "name": "Mechanism", "a": "C terminal fragment of growth hormone (residues 177 to 191) proposed to stimulate fat breakdown and inhibit fat synthesis without raising IGF-1 or glucose.", "b": "GLP-1 receptor agonist that reduces appetite through the brain, slows gastric emptying, raises glucose dependent insulin, and lowers glucagon.", "source_ids": [ "ng-2000", "fda-wegovy-label" ] }, { "name": "Cardiovascular outcomes", "a": "None studied.", "b": "20% relative reduction in major adverse cardiovascular events in SELECT (hazard ratio 0.80) and 26% in type 2 diabetes in SUSTAIN-6 (hazard ratio 0.74).", "source_ids": [ "select", "sustain-6" ] }, { "name": "Side effects", "a": "No systematic human safety data; FDA cited serious adverse events with unclear causality and immunogenicity risk from impurities.", "b": "Nausea (44% versus 16% placebo), diarrhea, vomiting, constipation; gallbladder disease, rare pancreatitis, and a boxed warning for thyroid C cell tumors in rodents.", "source_ids": [ "fda-category-2", "step-1", "fda-wegovy-label" ] }, { "name": "FDA and compounding status", "a": "Not FDA approved. Placed in 503A Category 2 in 2023; the nomination is now listed as withdrawn, so it is not on the bulks list and cannot be lawfully compounded.", "b": "FDA approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021). Shortage based compounding ended in 2025 (503A by April 22, 503B by May 22).", "source_ids": [ "fda-category-2", "fda-503a-bulks", "fda-glp1-compounding" ] }, { "name": "WADA status", "a": "Prohibited at all times under S2 as a growth hormone fragment.", "b": "Not prohibited.", "source_ids": [ "wada-list" ] }, { "name": "Route and dosing", "a": "Not established in humans; mice received roughly 250 ug/kg to 2 mg/kg per day.", "b": "Wegovy: 0.25 mg weekly, increased every 4 weeks to a 2.4 mg weekly maintenance dose; oral tablets also available.", "source_ids": [ "heffernan-2001-endo", "step-1", "fda-wegovy-label" ] }, { "name": "Cost and access", "a": "No lawful source. Research chemical vials are not lawful for human use and are not verified.", "b": "Wegovy list price about 1,349 USD per month; manufacturer cash pricing roughly 349 to 499 USD; 0 to 25 USD with commercial coverage and a savings card.", "source_ids": [ "fda-503a-bulks", "fda-wegovy-label" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Does AOD-9604 work for weight loss like semaglutide?", "a": "There is no published human evidence that it does. AOD-9604 reduced fat mass in obese mice, but the sponsor's human obesity trials did not produce an indexed positive result and the program was discontinued. Semaglutide produced 14.9% average weight loss in the 68 week STEP 1 trial.", "source_ids": [ "heffernan-2001-endo", "step-1" ] }, { "q": "Is AOD-9604 safer than semaglutide?", "a": "It is not known to be. AOD-9604 has no systematic human safety data, and FDA cited serious adverse events of unclear causality when it placed it in Category 2. Semaglutide has well characterized side effects, mainly gastrointestinal, from trials involving tens of thousands of people.", "source_ids": [ "fda-category-2", "step-1", "fda-wegovy-label" ] }, { "q": "Can I get AOD-9604 from a compounding pharmacy?", "a": "Not lawfully. FDA lists AOD-9604's nomination as withdrawn from Category 2, and it is not on the 503A bulks list, so there is no basis for a pharmacy to compound it.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Can athletes use either one?", "a": "AOD-9604 is prohibited at all times under WADA section S2 as a growth hormone fragment. Semaglutide is not on the prohibited list.", "source_ids": [ "wada-list" ] }, { "q": "What if semaglutide is too expensive?", "a": "The manufacturer sells Wegovy direct to consumers at roughly 349 to 499 USD per month, and commercial coverage with a savings card can bring the cost to 25 USD or less. Compounded semaglutide is no longer permitted for routine use since the 2025 shortage resolution.", "source_ids": [ "fda-wegovy-label", "fda-glp1-compounding" ] } ], "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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" }, { "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" }, { "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" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "bpc-157-vs-ara-290", "a": "bpc-157", "b": "ara-290", "title": "BPC-157 vs ARA-290 (cibinetide)", "summary": "ARA-290 has much stronger evidence: four small placebo controlled human trials show it improved neuropathy symptoms and regrew corneal nerve fibers in sarcoidosis and type 2 diabetes. BPC-157 has no controlled human trial and rests on rodent healing studies. Neither has a lawful path today: ARA-290 is an investigational drug that cannot lawfully be compounded, and BPC-157, though off the FDA Category 2 list and recommended for the 503A bulks list in July 2026, awaits an FDA final rule.", "verdict": { "winner": "b", "rationale": "On evidence grade, ARA-290 wins clearly: it is graded human RCT from phase 2 trials (for example, 64 patients in a phase 2b trial with a significant increase in corneal nerve fiber area), while BPC-157 is animal only. The trials are small, short, and developer sponsored, and ARA-290 has no lawful access outside a clinical trial. BPC-157 has a PCAC recommendation awaiting an FDA final rule but no human proof, so ARA-290 is the better supported peptide even though it is harder to obtain lawfully.", "source_ids": [ "culver-2017", "heij-2012", "brines-2015", "gwyer-2019", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic 15 amino acid fragment of a gastric protein (body protection compound).", "b": "Investigational 11 amino acid peptide copying helix B of erythropoietin, engineered to activate the innate repair receptor without raising red blood cells.", "source_ids": [ "sikiric-2011", "dahan-2014-review" ] }, { "name": "Evidence grade", "a": "Animal only. No controlled human trial; three small uncontrolled pilot reports from one clinic.", "b": "Human RCT. Four small phase 2 placebo controlled trials of 4 weeks or 28 days.", "source_ids": [ "gwyer-2019", "heij-2012", "dahan-2013", "culver-2017", "brines-2015", "mcguire-2025" ] }, { "name": "Main use studied", "a": "Tendon, ligament, muscle, and gut healing in rodents.", "b": "Small fiber neuropathy in sarcoidosis and painful neuropathy in type 2 diabetes in humans.", "source_ids": [ "chang-2011", "sikiric-2011", "culver-2017", "brines-2015" ] }, { "name": "Key results", "a": "Faster rat Achilles tendon healing; healing of NSAID ulcers and fistulas in rodents.", "b": "Neuropathy screening score improved 11.5 vs 2.9 points with placebo in 22 patients; corneal nerve fiber area rose significantly in a 64 patient phase 2b trial; HbA1c and neuropathic pain improved in type 2 diabetes.", "source_ids": [ "chang-2011", "sikiric-2011", "heij-2012", "culver-2017", "brines-2015" ] }, { "name": "Mechanism", "a": "Growth factor receptor upregulation, nitric oxide modulation, and angiogenesis in animal models.", "b": "Binds only the tissue protective innate repair receptor (erythropoietin receptor plus beta common receptor), avoiding the red cell, clotting, and blood pressure effects of erythropoietin.", "source_ids": [ "sikiric-2016", "dahan-2014-review" ] }, { "name": "Human safety data", "a": "None systematic. Three small uncontrolled pilot reports (about 30 people) reported no adverse events; anecdotal injection site reactions.", "b": "No safety concerns in 28 day trials and no rise in hemoglobin; long term safety unknown.", "source_ids": [ "gwyer-2019", "heij-2012", "culver-2017", "mcguire-2025" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet.", "b": "Investigational, not approved anywhere; not a component of an approved drug and not on the bulks list, so it cannot lawfully be compounded. Access only inside a clinical trial.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Routes in the literature", "a": "Not established in humans; rodent studies used injection, drinking water, or topical application, and the human pilot reports used injections.", "b": "Subcutaneous injection in the main phase 2 trials and intravenous infusion in the pilot trial. No lawful product exists outside a trial.", "source_ids": [ "gwyer-2019", "culver-2017", "heij-2012", "mcguire-2025" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Prohibited under S0 as a non-approved substance; as an erythropoietin derived peptide it is also relevant to S2.", "source_ids": [ "wada-list-s0", "wada-list-ara" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which has better human evidence, BPC-157 or ARA-290?", "a": "ARA-290. It has four small placebo controlled trials in people with neuropathy, including a 64 patient phase 2b trial showing corneal nerve regrowth. BPC-157 has no controlled human trial, only three small uncontrolled pilot reports from one clinic.", "source_ids": [ "culver-2017", "heij-2012", "gwyer-2019", "mcguire-2025" ] }, { "q": "Can I get ARA-290 from a compounding pharmacy?", "a": "No. Cibinetide is investigational, is not a component of an approved drug, and is not on the 503A bulks list, so neither 503A pharmacies nor 503B outsourcing facilities can lawfully make it. The only lawful access is a registered clinical trial.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Does ARA-290 raise red blood cells like EPO?", "a": "No. It was designed to bind only the tissue repair receptor and did not raise hemoglobin or hematocrit in trials.", "source_ids": [ "dahan-2014-review", "heij-2012" ] }, { "q": "Is either one useful for tendon injuries?", "a": "Neither has human tendon data. BPC-157 has rodent tendon studies; ARA-290 was studied for nerve damage, not tendons.", "source_ids": [ "chang-2011", "culver-2017" ] }, { "q": "Are BPC-157 and ARA-290 allowed in sport?", "a": "No. Both are prohibited on the WADA Prohibited List: BPC-157 under S0, and ARA-290 under S0 with an erythropoietin link relevant to S2.", "source_ids": [ "wada-list-s0", "wada-list-ara" ] } ], "sources": [ { "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": "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": "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": "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": "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": "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": "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": "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": "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": "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": "wada-list-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-list-ara", "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 }, { "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "BPC-157 vs ARA-290: human evidence and legal status", "description": "BPC-157 vs ARA-290 (cibinetide): placebo controlled neuropathy trials vs rodent healing data, safety, WADA status, and why neither has a lawful path today." } }, { "slug": "bpc-157-vs-ghk-cu", "a": "bpc-157", "b": "ghk-cu", "title": "BPC-157 vs GHK-Cu", "summary": "GHK-Cu has the stronger footing: it has small human studies of topical creams for aged and photodamaged skin, and topical GHK-Cu is sold lawfully as a cosmetic ingredient without a prescription. BPC-157 has no controlled human trial and rests on rodent tendon and gut studies, though it came off the FDA Category 2 list in April 2026 and was recommended for the 503A bulks list. They target different problems: GHK-Cu is a skin and wound peptide, BPC-157 is promoted for tendon, ligament, and gut healing, and neither has human data for injection.", "verdict": { "winner": "b", "rationale": "GHK-Cu is graded human observational because controlled cosmetic studies of topical creams report improved skin firmness, elasticity, and wrinkles, and topical products are lawful to buy. BPC-157 is graded animal only, with no controlled human trial, and it has no lawful compounded path until FDA publishes a final rule. The edge applies to topical skin use; for tendon or gut problems neither has human evidence, and the GHK-Cu human data are small studies summarized mostly by the peptide's discoverer.", "source_ids": [ "pickart-2015", "pickart-2008", "gwyer-2019", "fda-cosmetics-vs-drugs", "fda-503a-bulks" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic 15 amino acid fragment of a gastric protein (body protection compound).", "b": "Naturally occurring tripeptide (glycyl-histidyl-lysine) bound to copper, found in human plasma, saliva, and urine.", "source_ids": [ "sikiric-2011", "pickart-2008" ] }, { "name": "Evidence grade", "a": "Animal only. No controlled human trial; human data limited to three small uncontrolled pilot reports from one clinic.", "b": "Human observational for topical skin use: small controlled cosmetic studies, cited through reviews. No human trial of injected GHK-Cu.", "source_ids": [ "gwyer-2019", "pickart-2015", "mcguire-2025" ] }, { "name": "Main use case in the literature", "a": "Tendon, ligament, muscle, and gastrointestinal healing in rodents, including NSAID induced ulcers and fistulas.", "b": "Skin aging and photodamage in humans (topical), plus wound, hair follicle, and bone healing in rodents, pigs, and dogs.", "source_ids": [ "chang-2011", "sikiric-2011", "pickart-2015", "pickart-2018" ] }, { "name": "Proposed mechanism", "a": "Growth factor receptor upregulation, nitric oxide system modulation, and VEGFR2 driven angiogenesis in animal and cell models.", "b": "Delivers copper to cells, attracts repair cells, increases collagen, elastin, and glycosaminoglycan synthesis, and dampens NF-kB and TNF-alpha signaling in cell and animal models.", "source_ids": [ "sikiric-2016", "pickart-2008", "pickart-2018" ] }, { "name": "Routes with data", "a": "Injection, oral in drinking water, and topical in rodents. No human route has published data.", "b": "Topical cream or serum in humans (the only form with human data). Injection has no human data.", "source_ids": [ "sikiric-2011", "pickart-2015" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list in July 2026; no final rule yet. Not FDA approved.", "b": "Topical: lawful cosmetic ingredient if no drug claims are made. Injectable: nomination withdrawn, so it is no longer in Category 2 but is not on the bulks list and was not reviewed by PCAC. Not FDA approved as a drug.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "fda-cosmetics-vs-drugs" ] }, { "name": "Access without a prescription", "a": "None lawful. Research chemical products are not lawful for human use.", "b": "Topical cosmetic products are sold over the counter. Injectable GHK-Cu has no lawful compounded path: it is off Category 2 but not on the 503A bulks list.", "source_ids": [ "fda-503a-bulks", "fda-cosmetics-vs-drugs" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Not named on the list. Topical cosmetic use is not a recognized concern, but injected GHK-Cu may fall under S0 as a non-approved substance, so status is unclear.", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "Topical cosmetic serums and creams roughly 20 to 100 USD per bottle. No lawful compounded price for injectable GHK-Cu, which is not on the 503A bulks list.", "source_ids": [ "fda-503a-bulks", "fda-cosmetics-vs-drugs" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for skin, BPC-157 or GHK-Cu?", "a": "GHK-Cu. Small controlled cosmetic studies of topical GHK-Cu creams report tighter skin, better elasticity and density, and fewer fine lines, and those products are sold over the counter. BPC-157 has no human skin data.", "source_ids": [ "pickart-2015", "pickart-2008", "fda-cosmetics-vs-drugs" ] }, { "q": "Which is better for tendon or joint injuries?", "a": "Neither has human evidence for tendon or joint injuries. BPC-157 has rodent tendon studies showing faster Achilles healing; GHK-Cu animal data focus on skin, hair follicle, and bone healing. Standard care remains physical therapy and load management.", "source_ids": [ "chang-2011", "gwyer-2019", "pickart-2018" ] }, { "q": "Is injectable GHK-Cu better studied than injectable BPC-157?", "a": "No. Neither has a controlled human trial of injection. BPC-157 has three small uncontrolled pilot reports from one clinic, and GHK-Cu's human data come only from topical cosmetic products, which tell you nothing about injected doses or safety.", "source_ids": [ "mcguire-2025", "pickart-2015" ] }, { "q": "Can I get either one legally?", "a": "Only topical GHK-Cu, which is sold as a cosmetic ingredient in creams and serums as long as no drug claims are made. Neither BPC-157 nor injectable GHK-Cu has a lawful compounded path today: BPC-157 awaits an FDA final rule after the July 2026 advisory committee vote, and injectable GHK-Cu is off Category 2 but not on the 503A bulks list. Research chemical vials are not lawful for human use.", "source_ids": [ "fda-cosmetics-vs-drugs", "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Do both carry a cancer concern?", "a": "Both have a theoretical concern because they promote angiogenesis or cell proliferation in animal and cell models, though neither has been shown to promote tumors in humans. Reviews of GHK also report anti-cancer activity in vitro, so the question is unresolved.", "source_ids": [ "sikiric-2016", "pickart-2018" ] } ], "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": "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-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": "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "BPC-157 vs GHK-Cu: evidence, uses, and legal status", "description": "BPC-157 vs GHK-Cu: which has human evidence, what each is studied for, safety and cancer questions, and why only topical GHK-Cu is lawful to buy in 2026." } }, { "slug": "bpc-157-vs-kpv", "a": "bpc-157", "b": "kpv", "title": "BPC-157 vs KPV", "summary": "Neither BPC-157 nor KPV has a controlled human trial, so neither is proven for gut or tissue healing in people. Both came off the FDA 503A Category 2 list on April 15, 2026 and were recommended for the 503A bulks list by the Pharmacy Compounding Advisory Committee in July 2026, with no final rule yet. The difference is focus: KPV is an anti-inflammatory fragment of alpha-MSH tested in mouse colitis, while BPC-157 is a gastric peptide fragment tested mostly in rat tendon, muscle, and gut injury.", "verdict": { "winner": "depends", "rationale": "The two share the same evidence grade (animal only) and the same regulatory status, and both are prohibited in sport, so neither wins on the criteria that matter most. For intestinal inflammation, KPV has two independent 2008 mouse colitis studies with a defined uptake mechanism (PepT1); for tendon or musculoskeletal injury, BPC-157 has the more relevant rodent data, though mostly from one research group. The choice depends on the problem, and in both cases standard medical care should come first because no human data exist.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008", "gwyer-2019", "chang-2011", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic 15 amino acid fragment of a gastric protein (body protection compound).", "b": "Synthetic tripeptide (lysine-proline-valine), the C-terminal fragment of alpha-melanocyte stimulating hormone.", "source_ids": [ "sikiric-2011", "dalmasso-2008" ] }, { "name": "Proposed mechanism", "a": "Growth factor receptor upregulation, nitric oxide system modulation, and VEGFR2 driven angiogenesis in animal and cell models.", "b": "Taken into gut epithelial and immune cells by the PepT1 transporter, then inhibits NF-kB and MAP kinase signaling and cytokine release. Works without the MC1 receptor and does not cause pigmentation.", "source_ids": [ "sikiric-2016", "dalmasso-2008", "kannengiesser-2008" ] }, { "name": "Main animal evidence", "a": "Rat Achilles tendon transection healed faster with more fibroblast outgrowth and migration; rodent studies report healing of NSAID ulcers, fistulas, and anastomoses.", "b": "Oral KPV reduced DSS and TNBS colitis in mice; a second lab found faster recovery, weight regain, and less inflammation in DSS and T cell transfer colitis.", "source_ids": [ "chang-2011", "sikiric-2011", "dalmasso-2008", "kannengiesser-2008" ] }, { "name": "Independence of the research base", "a": "Mostly a small number of laboratories, largely in Zagreb, with limited independent replication.", "b": "Two independent laboratories published consistent mouse colitis results in 2008; the total body of work is small.", "source_ids": [ "gwyer-2019", "dalmasso-2008", "kannengiesser-2008" ] }, { "name": "Human evidence", "a": "No controlled human trial. Three small uncontrolled pilot reports from one clinic (knee pain, interstitial cystitis, and intravenous safety) reported benefit or no adverse events but had no comparison group.", "b": "No indexed human trial for any indication.", "source_ids": [ "gwyer-2019", "dalmasso-2008", "mcguire-2025" ] }, { "name": "Theoretical safety concern", "a": "Promotes angiogenesis in animals, so a theoretical concern about growth of existing tumors has been raised (not shown in humans).", "b": "Dampens NF-kB driven immune signaling, so a theoretical concern about impaired response to infection has been raised (not shown in humans).", "source_ids": [ "sikiric-2016", "dalmasso-2008" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet.", "b": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet.", "note": "Identical status. Neither is FDA approved or eligible for 503B outsourcing.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Prohibited at all times under S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price. KPV is sold in oral and injectable forms, neither lawfully compounded.", "note": "Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for gut inflammation or IBD, BPC-157 or KPV?", "a": "Neither has been tested in people with inflammatory bowel disease. KPV has two independent mouse colitis studies showing less inflammation and faster recovery; BPC-157 has rodent data on ulcers, fistulas, and NSAID injury. Approved IBD treatments with human trial data remain the standard.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008", "sikiric-2011" ] }, { "q": "Does KPV cause tanning like other alpha-MSH peptides?", "a": "No. KPV is only the last three amino acids of alpha-MSH, and in mice its anti-inflammatory effect did not depend on the MC1 receptor that drives pigmentation.", "source_ids": [ "kannengiesser-2008" ] }, { "q": "Can a pharmacy compound BPC-157 or KPV?", "a": "No, not from bulk today. Both were removed from FDA's 503A Category 2 list on April 15, 2026, and PCAC recommended both for the 503A bulks list in July 2026, but that recommendation is advisory. Until FDA publishes a final rule, neither is on the 503A bulks list, so a 503A pharmacy has no federal basis to compound them from bulk, and state boards cannot authorize what federal law does not.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are BPC-157 and KPV allowed in sport?", "a": "No. Both are prohibited at all times under S0 of the WADA Prohibited List as non-approved substances.", "source_ids": [ "wada-list" ] }, { "q": "Has either one been studied in people?", "a": "Not in a controlled trial. KPV has no published human study of any kind. BPC-157 has three small uncontrolled pilot reports from one clinic, none of which tested gut disease. Neither has a human dose finding study, so dose figures circulating online come from animal work or sellers, not from human data.", "source_ids": [ "mcguire-2025", "dalmasso-2008" ] } ], "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": "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": "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": "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": "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": "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": "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "BPC-157 vs KPV: gut healing evidence and legal status", "description": "BPC-157 vs KPV for gut inflammation and healing: what the rodent and mouse studies show, human data, safety concerns, and their shared 2026 FDA status." } }, { "slug": "bpc-157-vs-tb-500", "a": "bpc-157", "b": "tb-500", "title": "BPC-157 vs TB-500", "summary": "Neither BPC-157 nor TB-500 has a controlled human trial of the injectable product, so neither is proven to speed healing in people. Both rest on rodent studies, both came off the FDA 503A Category 2 list on April 15, 2026, and both were recommended for the 503A bulks list by the Pharmacy Compounding Advisory Committee in July 2026 without a final FDA rule yet. They differ mainly in which animal models support them: BPC-157 in tendon and gut healing, thymosin beta-4 (the parent of TB-500) in skin wounds and cardiac repair.", "verdict": { "winner": "depends", "rationale": "The two are tied on the things that matter most: both are graded animal only for the injectable form, both have the same regulatory status (off Category 2, recommended by PCAC, not yet on the bulks list), and both are prohibited by WADA. BPC-157's animal data are more specific to tendon and gastrointestinal injury but come mostly from one research group; thymosin beta-4 has independent skin wound and cardiac studies and one human eye drop trial, but products sold as TB-500 may be a fragment rather than the full peptide. The honest answer is that no human evidence favors either, and the choice depends on which animal model is closer to the problem.", "source_ids": [ "gwyer-2019", "chang-2011", "malinda-1999", "sosne-2015", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic 15 amino acid fragment of a gastric protein (body protection compound). Not found as such in the body.", "b": "Synthetic version or fragment of thymosin beta-4, a 43 amino acid actin binding peptide present in nearly all human cells. Some products claim to be only the LKKTETQ fragment.", "source_ids": [ "sikiric-2011", "goldstein-2012" ] }, { "name": "Proposed mechanism", "a": "Upregulates growth factor receptor signaling, modulates the nitric oxide system, and promotes angiogenesis through VEGFR2 in animal and cell models.", "b": "Sequesters G-actin to support cell migration, activates the ILK and Akt survival pathway, and reduces inflammation and scarring in animal and cell models.", "source_ids": [ "sikiric-2016", "chang-2011", "bock-marquette-2004", "goldstein-2012" ] }, { "name": "Strongest animal evidence", "a": "Rat Achilles tendon transection: faster healing and more tendon fibroblast outgrowth, survival, and migration. Rodent gut studies report healing of NSAID ulcers, fistulas, and anastomoses.", "b": "Rat full thickness wounds: reepithelialization up 42% at day 4 and up to 61% at day 7. Mouse heart attack model: better cardiomyocyte survival and cardiac function.", "source_ids": [ "chang-2011", "sikiric-2011", "malinda-1999", "bock-marquette-2004" ] }, { "name": "Human evidence", "a": "No controlled human trial. Three small uncontrolled pilot reports from one clinic (knee pain, interstitial cystitis, and intravenous safety) reported benefit or no adverse events but had no comparison group.", "b": "No human trial of injected TB-500 products. One phase 2 trial of 0.1% thymosin beta-4 eye drops in 72 adults with dry eye missed both primary endpoints, and phase 1 intravenous studies of full length thymosin beta-4 in healthy volunteers found it well tolerated; neither tested injury healing.", "source_ids": [ "gwyer-2019", "sosne-2015", "mcguire-2025", "ruff-2010" ] }, { "name": "Independence of the research base", "a": "Most studies come from a small number of laboratories, mostly in Zagreb, with limited independent replication.", "b": "Wound and cardiac findings come from several independent groups, including a Nature paper on cardiac repair.", "source_ids": [ "gwyer-2019", "bock-marquette-2004", "malinda-1999" ] }, { "name": "Routes in the literature", "a": "Rodent work used intraperitoneal injection, oral dosing in drinking water, and topical application; BPC-157 is reported to be active orally in animals.", "b": "Rodent work used topical application and intraperitoneal injection; the only human use is topical eye drops.", "source_ids": [ "sikiric-2011", "malinda-1999", "sosne-2015" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list in July 2026; no final rule yet. Not FDA approved.", "b": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list in July 2026; no final rule yet. Not FDA approved.", "note": "Identical status today: neither is on the 503A bulks list, so a 503A pharmacy has no federal basis to compound either from bulk.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Prohibited at all times under S2; thymosin beta-4 and TB-500 are named on the list.", "source_ids": [ "wada-list-s0", "wada-list" ] }, { "name": "Typical cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price. Often marketed alongside BPC-157, which has the same status.", "note": "Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for tendon injuries, BPC-157 or TB-500?", "a": "Neither has been tested in a published human trial for tendon injury. BPC-157 has the more tendon specific animal data (rat Achilles transection and tendon explant studies), while thymosin beta-4 data are mainly in skin wounds and heart tissue. Standard care for tendon injury remains load management and physical therapy.", "source_ids": [ "chang-2011", "gwyer-2019", "malinda-1999" ] }, { "q": "Is there any human evidence for TB-500?", "a": "Only indirectly. A phase 2 trial of 0.1% thymosin beta-4 eye drops in 72 adults with dry eye did not meet its primary endpoints, though some secondary endpoints improved, and a phase 1 intravenous study of full length thymosin beta-4 in healthy volunteers found it well tolerated. No human trial of injected TB-500 for any injury has been published.", "source_ids": [ "sosne-2015", "ruff-2010" ] }, { "q": "Can a pharmacy legally compound BPC-157 and TB-500 now?", "a": "No, not from bulk today. Both were removed from FDA's 503A Category 2 list on April 15, 2026, and PCAC recommended both for the 503A bulks list in July 2026, but that recommendation is advisory. Until FDA publishes a final rule, neither is on the 503A bulks list, so a 503A pharmacy has no federal basis to compound them from bulk, and state boards cannot authorize what federal law does not. Neither is eligible for 503B outsourcing.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are BPC-157 and TB-500 banned in sport?", "a": "Yes. BPC-157 is prohibited at all times under S0 (non-approved substances), and thymosin beta-4 and TB-500 are named under S2 of the WADA Prohibited List.", "source_ids": [ "wada-list-s0", "wada-list" ] }, { "q": "Is stacking BPC-157 and TB-500 supported by evidence?", "a": "No. No controlled study in animals or people has tested the two together, so claims of synergy are not supported by published data. The only published human report that used both was a retrospective knee pain survey in which 4 people received the pair, with no comparison group. Both share a theoretical concern about promoting existing tumors because they drive angiogenesis or cell migration in animal models.", "source_ids": [ "lee-2021", "gwyer-2019", "goldstein-2012" ] } ], "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": "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-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "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": "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 }, { "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "BPC-157 vs TB-500: differences, evidence, legal status", "description": "BPC-157 vs TB-500: how the two healing peptides differ in animal and human evidence, safety, WADA status, and their shared 2026 FDA compounding status." } }, { "slug": "cagrilintide-vs-pramlintide", "a": "cagrilintide", "b": "pramlintide", "title": "Cagrilintide vs pramlintide", "summary": "Both are amylin analogs, but they sit at opposite ends of the pipeline. Pramlintide (Symlin) has been FDA approved since 2005 as a mealtime add-on to insulin, injected before each major meal, and lowers HbA1c by roughly 0.3 to 0.4 points more than placebo with 1 to 2 kg of weight loss. Cagrilintide is an investigational once weekly analog that produced up to 10.8% weight loss alone and 20.4% with semaglutide, but it is not approved and cannot be lawfully obtained outside a trial.", "verdict": { "winner": "depends", "rationale": "For someone on mealtime insulin who needs better glucose control today, pramlintide is the only lawful choice: it is FDA approved with year long randomized trials, though its effect is modest and it carries a boxed warning for severe hypoglycemia. For weight loss, cagrilintide's evidence is far stronger (10.8% at 26 weeks versus about 3.6 kg placebo corrected at 16 weeks for pramlintide), but it is investigational, has no lawful compounding path, and is prohibited in sport. No trial has compared them directly.", "source_ids": [ "fda-symlin-label", "hollander-2003", "whitehouse-2002", "aronne-2007", "cagrilintide-phase2", "redefine-1", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Molecule and duration", "a": "Acylated long acting amylin analog that binds albumin for once weekly dosing.", "b": "Human amylin with three proline substitutions to stop aggregation; short acting, injected immediately before each major meal.", "source_ids": [ "cagrilintide-phase2", "fda-symlin-label" ] }, { "name": "Approved or studied use", "a": "Studied for chronic weight management, alone and combined with semaglutide 2.4 mg (CagriSema). No approved use.", "b": "FDA approved as an adjunct to mealtime insulin in type 1 and type 2 diabetes when glucose is not controlled. Weight loss is off label.", "source_ids": [ "cagrilintide-phase2", "redefine-1", "fda-symlin-label" ] }, { "name": "Weight loss evidence", "a": "Phase 2 (706 adults, 26 weeks): 6.0% to 10.8% across 0.3 to 4.5 mg versus 3.0% on placebo. With semaglutide: 20.4% versus 3.0% at 68 weeks in REDEFINE 1.", "b": "Obesity phase 2 (204 adults, 16 weeks): about 3.6 kg placebo corrected loss at up to 240 ug three times daily. In insulin treated type 2 diabetes: minus 1.4 kg versus a 0.7 kg gain over 52 weeks.", "source_ids": [ "cagrilintide-phase2", "redefine-1", "aronne-2007", "hollander-2003" ] }, { "name": "Glucose lowering evidence", "a": "Phase 2 in type 2 diabetes (92 adults, 32 weeks) tested it only in combination with semaglutide, with clinically relevant HbA1c improvement.", "b": "Type 1 diabetes: HbA1c down about 0.4 versus 0.1 points (480 adults, 52 weeks). Type 2 diabetes on insulin: 0.62 versus 0.22 points (656 adults, 52 weeks).", "source_ids": [ "cagrisema-t2d-phase2", "whitehouse-2002", "hollander-2003" ] }, { "name": "Key safety concerns", "a": "Nausea in 20% to 47% across doses versus 18% on placebo; long term safety and outcomes not yet reported.", "b": "Boxed warning for severe insulin induced hypoglycemia within 3 hours of injection; mealtime insulin is cut by 50% at start. Nausea in 28% to 48% in trials. Contraindicated in gastroparesis and hypoglycemia unawareness.", "source_ids": [ "cagrilintide-phase2", "fda-symlin-label" ] }, { "name": "Dosing", "a": "Trial regimens only: once weekly subcutaneous, escalated to 0.3 to 4.5 mg alone or 2.4 mg with semaglutide.", "b": "Symlin label: type 1 diabetes 15 ug before meals titrated to 30 or 60 ug; type 2 diabetes 60 ug titrated to 120 ug before meals.", "source_ids": [ "cagrilintide-phase2", "redefine-1", "fda-symlin-label" ] }, { "name": "Regulatory and compounding status", "a": "Not FDA approved; not on the 503A bulks list and not a component of an approved drug, so it cannot be compounded.", "b": "FDA approved (Symlin, March 2005). Not in shortage, so compounding is limited to documented patient specific need.", "source_ids": [ "fda-503a-bulks", "fda-symlin-label" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S0 (non-approved substances).", "b": "Not on the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Are cagrilintide and pramlintide the same kind of drug?", "a": "Yes, both mimic amylin, a hormone released with insulin that slows stomach emptying, suppresses glucagon after meals, and increases fullness. Pramlintide is short acting and taken before meals; cagrilintide is engineered for once weekly dosing.", "source_ids": [ "fda-symlin-label", "cagrilintide-phase2" ] }, { "q": "Can pramlintide be used for weight loss instead of cagrilintide?", "a": "Not on label. Pramlintide is approved only as an add-on to mealtime insulin. An off label obesity trial found about 3.6 kg placebo corrected weight loss over 16 weeks at doses up to 240 ug three times daily, far less than cagrilintide's 10.8% at 26 weeks.", "source_ids": [ "fda-symlin-label", "aronne-2007", "cagrilintide-phase2" ] }, { "q": "Why does pramlintide have a boxed warning?", "a": "Because combined with mealtime insulin it can cause severe hypoglycemia, usually within 3 hours of the injection. The label requires cutting mealtime insulin by 50% when starting and excludes people with hypoglycemia unawareness.", "source_ids": [ "fda-symlin-label" ] }, { "q": "Can I get cagrilintide legally?", "a": "Only in a registered clinical trial. It is not FDA approved and is not on the 503A bulks list, so pharmacies cannot compound it; products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is either banned in sport?", "a": "Cagrilintide is prohibited at all times under WADA section S0 because it is not approved. Pramlintide is not on the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "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": "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": "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/search.cfm?labeltype=all&query=symlin" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, including section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "carnosine-vs-glutathione", "a": "carnosine", "b": "glutathione", "title": "Carnosine vs glutathione", "summary": "Carnosine has the stronger clinical evidence: meta-analyses of randomized trials found modest reductions in fasting glucose, HbA1c, and waist circumference, mostly in people with metabolic disease, and it is a simple, inexpensive oral supplement. Glutathione's randomized trials show that sustained oral dosing raises body glutathione stores, but none shows a clinical outcome, and the injectable form sold by clinics is compounded pending an FDA decision. Both are naturally occurring small peptides with antioxidant roles, and neither is prohibited in sport.", "verdict": { "winner": "a", "rationale": "Both are graded human RCT, but carnosine's trials reach surrogate clinical endpoints (glycemic control and central obesity in a 2020 meta-analysis, plus a 12 week trial in which carnosine prevented worsening insulin resistance), whereas glutathione's trials measure only tissue levels and oxidative stress markers, with one of two trials finding no change. Carnosine is also a lawful over the counter supplement with no injectable market, while injectable glutathione is a nominated bulk substance that has drawn FDA warnings about endotoxin contamination. The effects of carnosine are modest and no trial measured diabetes incidence or cardiovascular events.", "source_ids": [ "menon-2020", "de-courten-2016", "richie-2015", "allen-2011", "fda-503a-bulks", "fda-compounding-qa" ] }, "dimensions": [ { "name": "Structure", "a": "Dipeptide of beta-alanine and histidine, concentrated in skeletal muscle and brain.", "b": "Tripeptide of glutamate, cysteine, and glycine, present in nearly every cell.", "source_ids": [ "boldyrev-2013", "richie-2015" ] }, { "name": "Mechanism", "a": "Buffers acid in working muscle, chelates copper and zinc, and traps reactive aldehydes and sugars, reducing advanced glycation end products.", "b": "Neutralizes peroxides via glutathione peroxidases, regenerates vitamins C and E, and conjugates toxins for excretion.", "source_ids": [ "boldyrev-2013", "richie-2015" ] }, { "name": "Clinical trial outcomes", "a": "Meta-analysis: lower fasting glucose, HbA1c, and waist circumference. 12 week trial of 2 g per day in 30 overweight adults: insulin resistance and 2 hour glucose worsened on placebo but not on carnosine.", "b": "6 month trial of 250 or 1,000 mg per day in 54 adults: body stores rose up to about 30% to 35% and natural killer cell activity increased. 4 week trial of 500 mg twice daily in 40 adults: no change in oxidative stress markers.", "source_ids": [ "menon-2020", "de-courten-2016", "richie-2015", "allen-2011" ] }, { "name": "Inflammation and oxidative stress", "a": "A 2024 meta-analysis found reductions in tumor necrosis factor alpha and malondialdehyde.", "b": "No change in systemic oxidative stress biomarkers in the 4 week randomized trial.", "source_ids": [ "saadati-2024", "allen-2011" ] }, { "name": "Oral bioavailability", "a": "Rapidly broken down by serum carnosinase in humans; its precursor beta-alanine raises muscle carnosine about 60% in 4 weeks.", "b": "Long thought to be digested, but sustained daily oral dosing raised body stores; levels returned to baseline within a month of stopping.", "source_ids": [ "boldyrev-2013", "hill-2007", "richie-2015" ] }, { "name": "Regulatory status", "a": "Dietary supplement; no injectable product and no compounding history.", "b": "Oral: dietary supplement. Injectable: nominated 503A bulk substance compounded under FDA's interim policy, with FDA warnings about endotoxin contamination and skin lightening marketing.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa" ] }, { "name": "Side effects", "a": "Well tolerated at 2 g per day; beta-alanine causes harmless tingling.", "b": "Oral forms well tolerated; IV use can cause flushing and rare allergic reactions, and inhaled forms can worsen asthma.", "source_ids": [ "de-courten-2016", "hill-2007", "fda-compounding-qa" ] }, { "name": "Typical cost", "a": "Roughly 15 to 40 USD per month at 1 to 2 g per day.", "b": "Oral roughly 20 to 50 USD per month; IV infusions 100 to 300 USD each.", "source_ids": [ "menon-2020", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is the better antioxidant supplement?", "a": "Carnosine has more outcome data: pooled trials show modest improvements in blood sugar, waist size, and some inflammation markers. Glutathione trials show that daily oral doses raise body glutathione, but a 4 week trial found no change in oxidative stress markers and no trial shows a clinical benefit.", "source_ids": [ "menon-2020", "saadati-2024", "richie-2015", "allen-2011" ] }, { "q": "Does carnosine help blood sugar?", "a": "Modestly. A 2020 meta-analysis of randomized trials found lower fasting glucose and HbA1c, mostly in people with metabolic disease, and a 12 week trial found carnosine prevented worsening insulin resistance in overweight adults. It has not been shown to prevent diabetes.", "source_ids": [ "menon-2020", "de-courten-2016" ] }, { "q": "Is IV glutathione better than oral?", "a": "There is no randomized evidence that IV glutathione produces a clinical benefit, and FDA has warned about compounded injectable products with high endotoxin. The randomized evidence is for oral glutathione raising body stores.", "source_ids": [ "richie-2015", "fda-compounding-qa" ] }, { "q": "Should I take carnosine or beta-alanine?", "a": "For raising muscle carnosine, beta-alanine is more efficient because human blood breaks down carnosine quickly; 4 weeks of beta-alanine raised muscle carnosine about 60% and improved high intensity cycling capacity. The glucose trials used carnosine itself.", "source_ids": [ "hill-2007", "boldyrev-2013", "de-courten-2016" ] }, { "q": "Can athletes take either one?", "a": "Yes. Neither is on the WADA Prohibited List, though intravenous infusions above 100 mL per 12 hours outside legitimate hospital care are a prohibited method regardless of what is infused.", "source_ids": [ "wada-list" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (including section M2 on intravenous infusions)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "cerebrolysin-vs-semax", "a": "cerebrolysin", "b": "semax", "title": "Cerebrolysin vs Semax", "summary": "Cerebrolysin has much more evidence than semax, including large placebo controlled stroke trials and Cochrane reviews, but that evidence shows a small and uncertain benefit and a possible rise in serious adverse events in acute stroke. Semax has only open label Russian studies. Neither is FDA approved; semax was recommended for the 503A bulks list in July 2026, while Cerebrolysin, a porcine brain extract, has no US compounding or legal import path.", "verdict": { "winner": "a", "rationale": "Cerebrolysin is graded human RCT: CASTA randomized 1,070 acute stroke patients (no difference on the primary endpoint), CARS found better arm function after stroke rehabilitation in 208 patients, and Cochrane reviews rate the evidence low certainty. Semax is graded human observational, with no blinded placebo controlled trial. Cerebrolysin is also registered in many more countries. The win is on evidence, not access: in the United States Cerebrolysin cannot lawfully be obtained, while semax has a pending compounding path.", "source_ids": [ "casta", "cars", "cochrane-stroke-2020", "gusev-1997", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Enzymatically digested porcine brain extract: an undefined mixture of low molecular weight peptides and free amino acids.", "b": "A single defined synthetic heptapeptide, an analog of ACTH fragment 4-10.", "source_ids": [ "cochrane-stroke-2020", "dolotov-2006" ] }, { "name": "Evidence grade", "a": "Human RCT: multiple randomized placebo controlled trials and Cochrane reviews, mostly industry supported.", "b": "Human observational: open comparative Russian studies without blinding or placebo.", "source_ids": [ "cochrane-stroke-2020", "cochrane-vad-2019", "gusev-1997", "gusev-2018" ] }, { "name": "Acute stroke results", "a": "CASTA (1,070 patients): no difference on the 90 day combined endpoint; Cochrane 2020 (1,601 patients): no difference in death and a possible increase in non-fatal serious adverse events (RR 2.15).", "b": "Open studies reported faster regression of neurological deficit and better EEG measures when added to standard care.", "source_ids": [ "casta", "cochrane-stroke-2020", "gusev-1997" ] }, { "name": "Stroke rehabilitation and dementia", "a": "CARS (208 patients): better Action Research Arm Test scores at day 90. Alzheimer meta-analysis: small cognitive benefit at 4 weeks, not significant at 6 months. Vascular dementia: small benefit, very low certainty.", "b": "Fewer exacerbations reported in chronic cerebrovascular insufficiency; no dementia trials in indexed English literature.", "source_ids": [ "cars", "gauthier-2015", "cochrane-vad-2019", "gusev-2005" ] }, { "name": "Route and regimen in the literature", "a": "Intravenous infusion, typically 30 mL daily for 10 to 21 days after stroke; given in a clinic.", "b": "Intranasal drops, 12 to 18 mg per day for 5 to 10 days in acute stroke; lower doses for cognitive uses.", "source_ids": [ "casta", "cars", "gusev-1997" ] }, { "name": "Safety", "a": "Possible increase in non-fatal serious adverse events in acute stroke; dizziness, headache, and agitation in dementia trials at placebo like rates.", "b": "Nasal irritation; anxiety, irritability, or insomnia reported anecdotally; no systematic blinded safety data.", "source_ids": [ "cochrane-stroke-2020", "alvarez-2006", "gusev-1997" ] }, { "name": "FDA and US access", "a": "Never submitted to FDA. As an undefined animal derived mixture it is not eligible for 503A or 503B compounding, and personal importation is not lawful for routine use.", "b": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Not prohibited.", "b": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Does Cerebrolysin work for stroke?", "a": "The best evidence says the benefit is uncertain. The largest trial, CASTA with 1,070 patients, found no difference on its primary endpoint at 90 days, and the 2020 Cochrane review found no difference in death with a possible increase in non-fatal serious adverse events. A smaller rehabilitation trial, CARS, did find better arm function.", "source_ids": [ "casta", "cochrane-stroke-2020", "cars" ] }, { "q": "Is semax better studied than Cerebrolysin?", "a": "No. Semax has only open label Russian studies without placebo control, while Cerebrolysin has several randomized placebo controlled trials and Cochrane reviews, even though those reviews rate the certainty as low.", "source_ids": [ "gusev-1997", "cochrane-stroke-2020", "cochrane-vad-2019" ] }, { "q": "Can I get Cerebrolysin in the United States?", "a": "Not lawfully for routine use. It has never been submitted to FDA, it cannot be compounded because it is an undefined animal derived mixture, and personal importation does not meet FDA's narrow exceptions. It is a prescription drug in Austria, Russia, China, and other countries.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Can I get semax in the United States?", "a": "Not from bulk today. Semax came off FDA Category 2 on April 15, 2026 and PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory: until FDA publishes a final rule it is not on the bulks list, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Is Cerebrolysin helpful for Alzheimer disease?", "a": "Only modestly, if at all. An industry linked meta-analysis found a small cognitive benefit at 4 weeks that was not significant at 6 months, and a dose ranging trial found only the lowest dose improved cognition at 24 weeks.", "source_ids": [ "gauthier-2015", "alvarez-2006" ] } ], "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": "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": "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": "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": "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": "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": "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": "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "cjc-1295-vs-ipamorelin", "a": "cjc-1295", "b": "ipamorelin", "title": "CJC-1295 vs ipamorelin", "summary": "CJC-1295 has human data that ipamorelin lacks: a single injection raised growth hormone 2 to 10 fold for 6 or more days and IGF-1 1.5 to 3 fold for 9 to 11 days in two small randomized trials in healthy adults. Ipamorelin's human data are one small IV pharmacology study showing growth hormone release in healthy men, and its only randomized trial, for postoperative ileus, was negative. Legally they are in the same place: neither was ever approved, both were placed on FDA's 503A Category 2 list in 2023, both nominations were withdrawn, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "CJC-1295 is graded human_rct because randomized, placebo controlled pharmacology trials showed sustained GH and IGF-1 increases, while ipamorelin is graded animal_only for its marketed uses. The win is narrow: CJC-1295's trials measured hormones, not any clinical benefit, FDA cited increased heart rate and a systemic vasodilatory reaction among its serious adverse events, and both share the same no-lawful-compounding status. No trial has tested either drug, or the popular blend, for body composition.", "source_ids": [ "teichman-2006", "ionescu-2006", "raun-1998", "beck-2014", "fda-503a-bulks", "gobburu-1999" ] }, "dimensions": [ { "name": "Mechanism", "a": "GHRH(1-29) analog with four stabilizing substitutions and a drug affinity complex that binds albumin; acts on the pituitary GHRH receptor.", "b": "Pentapeptide ghrelin receptor (GHS-R1a) agonist; releases GH through a pathway separate from GHRH.", "source_ids": [ "jette-2005", "raun-1998" ] }, { "name": "Duration of action", "a": "Half life 5.8 to 8.1 days after subcutaneous injection; one dose raised IGF-1 for 9 to 11 days.", "b": "Short acting; no human pharmacokinetic publication for subcutaneous use. Animal ED50 studies used intravenous dosing.", "note": "The product sold as CJC-1295 without DAC (modified GRF 1-29) lacks the albumin linker, has a half life of about 30 minutes, and has no published human trials.", "source_ids": [ "teichman-2006", "raun-1998" ] }, { "name": "Human evidence", "a": "Two randomized, placebo controlled ascending dose trials (28 and 49 days) in healthy adults: GH up 2 to 10 fold and IGF-1 up 1.5 to 3 fold. A separate study showed trough GH up 7.5 fold with pulsatility preserved.", "b": "One randomized trial (117 adults after bowel resection, intravenous): time to first tolerated meal 25.3 versus 32.6 hours on placebo, not significant (p = 0.15). No human GH or IGF-1 outcomes published.", "source_ids": [ "teichman-2006", "ionescu-2006", "beck-2014" ] }, { "name": "Evidence grade", "a": "Human RCT (hormonal endpoints only, small trials, no clinical outcomes).", "b": "Animal only for GH related uses; the human ileus trial is for a different indication and route.", "source_ids": [ "teichman-2006", "raun-1998", "beck-2014" ] }, { "name": "Safety signals", "a": "Injection site reactions, flushing, headache; FDA's Category 2 evaluation cited increased heart rate and a systemic vasodilatory reaction. Sustained IGF-1 elevation is untested long term.", "b": "No safety signal versus placebo in the 7 day ileus trial (adverse events 87.5% versus 94.8%); FDA cited immunogenicity from aggregation and impurities.", "source_ids": [ "teichman-2006", "fda-503a-bulks", "beck-2014" ] }, { "name": "Literature dosing", "a": "Pharmacology trials only: single or repeated weekly or biweekly subcutaneous doses, with 30 or 60 ug/kg best tolerated.", "b": "Not established; the only human trial used 0.03 mg/kg intravenously twice daily for up to 7 days.", "source_ids": [ "teichman-2006", "beck-2014" ] }, { "name": "Regulatory status", "a": "Never approved; development for HIV lipodystrophy and GH deficiency discontinued. 503A Category 2 in September 2023, now a withdrawn nomination.", "b": "Never approved; development stopped after the ileus trial. 503A Category 2 in September 2023, nominations withdrawn in 2024; ipamorelin acetate also remains in 503B Category 2.", "note": "Neither was among the peptides reviewed by the Pharmacy Compounding Advisory Committee in July 2026. Both are prohibited under WADA section S2.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which raises growth hormone more, CJC-1295 or ipamorelin?", "a": "Only CJC-1295 has been measured in humans: one 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. Ipamorelin's GH effect is documented in rats and pigs, not in published human studies.", "source_ids": [ "teichman-2006", "raun-1998" ] }, { "q": "Is the CJC-1295 and ipamorelin blend proven?", "a": "No. No published trial has tested the combination. The rationale is that they act on different receptors (GHRH versus ghrelin), but efficacy and safety of the blend in humans are unknown.", "source_ids": [ "teichman-2006", "raun-1998" ] }, { "q": "Can a compounding pharmacy make either one legally?", "a": "No. FDA placed both on the 503A Category 2 list in September 2023; the nominations were later withdrawn, and neither is on the bulks list or a component of an approved drug, so licensed pharmacies have no lawful basis to compound them.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Is CJC-1295 without DAC the same drug?", "a": "No. The version sold as CJC-1295 without DAC (modified GRF 1-29) lacks the albumin binding group, lasts about 30 minutes instead of about a week, and has no published human trials under that name.", "source_ids": [ "teichman-2006", "jette-2005" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are named in WADA section S2 and are prohibited at all times.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (GHRH analogues and growth hormone secretagogues, including CJC-1295 and ipamorelin)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "dihexa-vs-semax", "a": "dihexa", "b": "semax", "title": "Dihexa vs Semax", "summary": "Semax is the better supported of the two: it has open label human studies in stroke, it is a registered prescription drug in Russia, and it was recommended for the FDA 503A bulks list in July 2026. Dihexa has never been given to people in a published study, its key mechanism paper was retracted in 2025, and its design paper carries an expression of concern. Dihexa also has no lawful US compounding path.", "verdict": { "winner": "b", "rationale": "Semax is graded human observational from Russian stroke studies without placebo control, which is weak but real human data. Dihexa is graded animal only, from one laboratory, with the HGF/c-Met mechanism paper retracted and the rat memory paper under an expression of concern, and no human safety data at all. On regulation, semax came off Category 2 and was recommended by PCAC for the 503A bulks list, while dihexa's nomination was withdrawn and it has no lawful compounding basis.", "source_ids": [ "gusev-1997", "gusev-2018", "mccoy-2013", "benoist-2014-retracted", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic oligopeptide derived from angiotensin IV (hexanoyl capped Tyr-Ile with an aminohexanoic amide tail).", "b": "Heptapeptide analog of ACTH fragment 4-10 with a stabilizing Pro-Gly-Pro tail.", "source_ids": [ "mccoy-2013", "dolotov-2006" ] }, { "name": "Proposed mechanism", "a": "Reported to bind hepatocyte growth factor and potentiate c-Met signaling to drive synapse formation; the paper establishing this was retracted in 2025.", "b": "Raised hippocampal BDNF protein about 1.4 fold and trkB expression within hours of one intranasal dose in rats.", "source_ids": [ "benoist-2014-retracted", "dolotov-2006" ] }, { "name": "Human evidence", "a": "None. No human pharmacokinetic, safety, or efficacy study of any kind.", "b": "Open comparative Russian studies in acute ischemic stroke and chronic cerebrovascular insufficiency reporting faster recovery and fewer exacerbations; no blinding or placebo.", "source_ids": [ "mccoy-2013", "gusev-1997", "gusev-2005", "gusev-2018" ] }, { "name": "Data integrity", "a": "Mechanism paper retracted (2025); design and rat memory paper under a 2021 expression of concern; no independent replication.", "b": "No retractions identified, but the clinical studies come from the developing research group and are published in Russian.", "source_ids": [ "benoist-2014-retracted", "mccoy-2013", "gusev-1997" ] }, { "name": "Theoretical safety concern", "a": "c-Met is an established oncogene, so potentiating it could plausibly promote tumor growth; no animal toxicology has been published.", "b": "Anxiety, irritability, insomnia, and nasal irritation reported; long term safety unknown.", "source_ids": [ "wright-harding-2015", "gusev-1997" ] }, { "name": "Route", "a": "Oral or injected in rats; sold as capsules, powder, or transdermal products without absorption data.", "b": "Intranasal drops (Russian product and most sold forms).", "source_ids": [ "mccoy-2013", "gusev-1997" ] }, { "name": "FDA and compounding status", "a": "Nomination withdrawn, so no longer in Category 2, but not on the bulks list and not recommended by PCAC in July 2026; no lawful compounding basis.", "b": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet. Registered prescription drug in Russia.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list-s0", "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is dihexa stronger than semax?", "a": "There is no human evidence that dihexa does anything in people. Claims that it is far more potent than BDNF come from the inventing laboratory's rat and cell work, and the paper describing its mechanism was retracted in 2025. Semax has open label human stroke studies, though none were placebo controlled.", "source_ids": [ "mccoy-2013", "benoist-2014-retracted", "gusev-1997" ] }, { "q": "Why was the dihexa paper retracted?", "a": "The 2014 journal article reporting that dihexa works through the HGF/c-Met system was retracted by the journal in April 2025, and the 2013 paper describing dihexa's design and rat memory effects carries a 2021 expression of concern. The mechanism should be treated as unconfirmed.", "source_ids": [ "benoist-2014-retracted", "mccoy-2013" ] }, { "q": "Can I get either one from a US pharmacy?", "a": "Semax may be available from some 503A pharmacies after the Pharmacy Compounding Advisory Committee recommended it for the bulks list in July 2026, depending on the state board. Dihexa has no lawful compounding basis: its nomination was withdrawn and it is not on the bulks list.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does dihexa carry a cancer risk?", "a": "Possibly, in theory. Dihexa is proposed to boost signaling through c-Met, a receptor that drives several cancers and is the target of approved cancer drugs. No toxicology study in animals or safety study in humans has been published to test this.", "source_ids": [ "wright-harding-2015", "mccoy-2013" ] }, { "q": "Are they allowed in sport?", "a": "Dihexa is prohibited at all times under S0 as a non-approved substance. Semax is not named on the list, but S0 could apply, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list-s0", "wada-list" ] } ], "sources": [ { "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-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": "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": "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": "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-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": "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": "wada-list-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "dulaglutide-vs-exenatide", "a": "dulaglutide", "b": "exenatide", "title": "Dulaglutide vs exenatide", "summary": "Dulaglutide wins on every measure that has been tested. In the AWARD-1 head-to-head trial, once weekly dulaglutide 1.5 mg lowered HbA1c by 1.51 points versus 0.99 with twice daily exenatide at 26 weeks, with less hypoglycemia, and in REWIND dulaglutide reduced cardiovascular events (hazard ratio 0.88) where exenatide's EXSCEL trial did not reach superiority. Branded exenatide was also discontinued in the United States in October 2024.", "verdict": { "winner": "a", "rationale": "AWARD-1 showed both dulaglutide doses were superior to twice daily exenatide for HbA1c at 26 and 52 weeks, dulaglutide needs one injection a week instead of fourteen, and it has a proven cardiovascular benefit. Exenatide's once weekly form was safe but not superior to placebo for cardiovascular events in EXSCEL, and both branded exenatide products were discontinued in October 2024.", "source_ids": [ "award-1", "rewind", "exscel", "exenatide-discontinuation" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Dulaglutide 1.5 mg and 0.75 mg weekly lowered HbA1c by 1.51 and 1.30 points at 26 weeks in AWARD-1, both superior to exenatide at 26 and 52 weeks.", "b": "Exenatide 10 micrograms twice daily lowered HbA1c by 0.99 points at 26 weeks (placebo 0.46).", "note": "AWARD-1 added treatment to metformin plus pioglitazone. Total hypoglycemia was lower with dulaglutide 1.5 mg than with exenatide.", "source_ids": [ "award-1" ] }, { "name": "Cardiovascular outcomes", "a": "REWIND: major adverse cardiovascular events hazard ratio 0.88 (95% CI 0.79 to 0.99) over a median 5.4 years in 9,901 adults; labeled for cardiovascular risk reduction.", "b": "EXSCEL: hazard ratio 0.91 (95% CI 0.83 to 1.00) in 14,752 adults; noninferior but not superior to placebo.", "source_ids": [ "rewind", "exscel", "fda-trulicity-label" ] }, { "name": "Dosing frequency", "a": "Once weekly injection, 0.75 mg up to 4.5 mg.", "b": "Twice daily injection before meals (5 then 10 micrograms), or 2 mg once weekly as the extended release form.", "source_ids": [ "fda-trulicity-label", "award-11", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Side effects", "a": "Nausea, vomiting, and diarrhea, mostly mild to moderate and transient in AWARD-1; boxed warning for thyroid C-cell tumors.", "b": "Nausea is the most common effect; the extended release form causes injection site nodules and carries the thyroid C-cell boxed warning, which the twice daily form does not.", "source_ids": [ "award-1", "fda-trulicity-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Market availability", "a": "Marketed as Trulicity, including for children 10 and older.", "b": "The manufacturer notified FDA that Byetta was discontinued on October 25, 2024 and Bydureon BCise on October 28, 2024; health plans moved members to other GLP-1 drugs.", "source_ids": [ "fda-trulicity-label", "exenatide-discontinuation" ] }, { "name": "Regulatory status", "a": "FDA approved (September 2014). 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.", "b": "FDA approved (Byetta 2005, Bydureon 2012) but no longer marketed. Never part of the shortage compounding era.", "source_ids": [ "fda-trulicity-label", "fda-byetta-label", "exenatide-discontinuation", "fda-glp1-shortage-updates", "fda-drug-shortages-dulaglutide" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not on the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [ { "pmid": "24879836", "title": "Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1)", "year": 2014, "design": "Randomized, placebo and active controlled phase 3 trial, 52 weeks (primary end point 26 weeks)", "population": "Adults with type 2 diabetes on metformin and pioglitazone, mean HbA1c 8.1%", "outcome": "HbA1c change minus 1.51 (dulaglutide 1.5 mg), minus 1.30 (0.75 mg), minus 0.99 (exenatide 10 micrograms twice daily), minus 0.46 (placebo) at 26 weeks; both dulaglutide doses superior to exenatide at 26 and 52 weeks", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/24879836/" } ], "faqs": [ { "q": "Is dulaglutide better than exenatide?", "a": "Yes on the direct evidence. In AWARD-1 both dulaglutide doses lowered HbA1c more than twice daily exenatide (1.51 and 1.30 versus 0.99 points at 26 weeks), with less hypoglycemia at 1.5 mg.", "source_ids": [ "award-1" ] }, { "q": "Can I still get exenatide?", "a": "Branded twice daily and once weekly exenatide were discontinued in the United States in October 2024, and health plans switched members to other GLP-1 drugs such as dulaglutide, liraglutide, or semaglutide.", "source_ids": [ "exenatide-discontinuation" ] }, { "q": "Do both lower cardiovascular risk?", "a": "Only dulaglutide has shown it: REWIND found a 12% relative reduction in major cardiovascular events. Once weekly exenatide was safe in EXSCEL but the reduction (hazard ratio 0.91) did not reach statistical superiority.", "source_ids": [ "rewind", "exscel" ] }, { "q": "How often is each injected?", "a": "Dulaglutide is injected once weekly. Exenatide was injected twice daily before meals as the immediate release form, or once weekly as the extended release form.", "source_ids": [ "fda-trulicity-label", "fda-byetta-label", "fda-bydureon-label" ] } ], "sources": [ { "id": "award-1", "type": "pubmed", "title": "Wysham C et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes (AWARD-1). Diabetes Care 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24879836/", "pmid": "24879836", "year": 2014 }, { "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": "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": "exenatide-discontinuation", "type": "other", "title": "Health plan provider notice: branded twice daily and once weekly exenatide discontinued in October 2024, accessed 2026-09-22", "url": "https://www.uhcprovider.com/en/resource-library/news/2024/discontinuation-bydureon-bcise-byetta.html", "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" }, { "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "dulaglutide-vs-mazdutide", "a": "dulaglutide", "b": "mazdutide", "title": "Dulaglutide vs mazdutide", "summary": "Mazdutide beat dulaglutide in two direct trials in Chinese adults with type 2 diabetes. In the 731 person phase 3 DREAMS-2 trial, mazdutide 4 mg and 6 mg lowered HbA1c 0.24 and 0.30 points more than dulaglutide 1.5 mg and weight 3.8% and 5.8% more at 28 weeks, at the cost of more gastrointestinal side effects. Dulaglutide remains the choice in the United States: it is FDA approved with a proven cardiovascular benefit (REWIND), while mazdutide is approved only in China.", "verdict": { "winner": "depends", "rationale": "On the head-to-head evidence mazdutide is superior for both glucose and weight (DREAMS-2 and a phase 2 trial). But dulaglutide has a completed cardiovascular outcomes trial, an FDA label that includes children 10 and older, and lawful US access, while mazdutide is approved only by China's regulator and cannot be compounded or sold in the United States. Where mazdutide is approved, the trial evidence favors it; in the United States, dulaglutide is the one that can be prescribed.", "source_ids": [ "dreams-2", "mazdutide-t2d-phase2", "rewind", "fda-trulicity-label", "mazdutide-china-t2d-approval", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Dulaglutide 1.5 mg weekly: HbA1c 1.35 points and weight 2.7% lower at 20 weeks in the phase 2 trial; reference arm in DREAMS-2.", "b": "Mazdutide: HbA1c 1.41 to 1.67 points and weight up to 7.1% lower at 20 weeks in phase 2; in DREAMS-2, HbA1c 0.24 (4 mg) and 0.30 (6 mg) points and weight 3.8% and 5.8% lower than dulaglutide at 28 weeks.", "note": "Both trials enrolled Chinese adults with type 2 diabetes; the phase 2 trial had 250 participants and DREAMS-2 had 731.", "source_ids": [ "mazdutide-t2d-phase2", "dreams-2" ] }, { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist (Fc fusion protein).", "b": "Dual GLP-1 and glucagon receptor agonist (oxyntomodulin analog).", "source_ids": [ "fda-trulicity-label", "glory-1" ] }, { "name": "Cardiovascular outcomes", "a": "REWIND: major adverse cardiovascular events hazard ratio 0.88 over a median 5.4 years in 9,901 adults; labeled for cardiovascular risk reduction in type 2 diabetes.", "b": "No cardiovascular outcomes trial has reported.", "source_ids": [ "rewind", "fda-trulicity-label", "glory-1" ] }, { "name": "Side effects", "a": "Nausea, diarrhea, vomiting, and abdominal pain; fewer gastrointestinal events than mazdutide in DREAMS-2.", "b": "Diarrhea 36%, decreased appetite 29%, nausea 23%, and vomiting 14% in the phase 2 trial; gastrointestinal events more frequent than with dulaglutide in DREAMS-2.", "source_ids": [ "dreams-2", "mazdutide-t2d-phase2", "fda-trulicity-label" ] }, { "name": "Weight management indication", "a": "None; approved for type 2 diabetes and cardiovascular risk reduction only.", "b": "Approved in China for chronic weight management (June 2025): 14.0% weight loss at 6 mg over 48 weeks in GLORY-1.", "source_ids": [ "fda-trulicity-label", "mazdutide-china-obesity-approval", "glory-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Trulicity, September 2014), including children 10 and older.", "b": "Approved in China for type 2 diabetes (September 2025) and weight management; not FDA approved and not eligible for US compounding.", "source_ids": [ "fda-trulicity-label", "mazdutide-china-t2d-approval", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not named on the list; with approval in China, section S0 may not apply. Confirm with the relevant anti-doping organization.", "source_ids": [ "wada-list" ] }, { "name": "Dosing", "a": "Once weekly injection, 0.75 mg escalated up to 4.5 mg.", "b": "Once weekly injection; 4 or 6 mg in the phase 3 diabetes and obesity trials.", "source_ids": [ "fda-trulicity-label", "dreams-2", "glory-1" ] } ], "head_to_head_studies": [ { "pmid": "41407860", "title": "Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes (DREAMS-2)", "year": 2026, "design": "Randomized phase 3 trial, 28 weeks", "n": 731, "population": "Chinese adults with type 2 diabetes on background oral antidiabetic drugs", "outcome": "HbA1c treatment difference minus 0.24 (4 mg) and minus 0.30 (6 mg) points versus dulaglutide 1.5 mg; weight difference minus 3.78% and minus 5.76%; more gastrointestinal adverse events with mazdutide", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/41407860/" }, { "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 controlled phase 2 trial with open label dulaglutide, 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 with mazdutide versus minus 1.35 with dulaglutide 1.5 mg; weight change up to minus 7.1% versus minus 2.7%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/" } ], "faqs": [ { "q": "Is mazdutide better than dulaglutide for type 2 diabetes?", "a": "In DREAMS-2, both mazdutide doses were superior to dulaglutide 1.5 mg, lowering HbA1c 0.24 to 0.30 points more and weight 3.8% to 5.8% more at 28 weeks, with more gastrointestinal side effects.", "source_ids": [ "dreams-2" ] }, { "q": "Does dulaglutide help with weight loss?", "a": "Modestly. It lowered weight by 2.7% at 20 weeks in the mazdutide phase 2 trial and has no weight management indication in the United States.", "source_ids": [ "mazdutide-t2d-phase2", "fda-trulicity-label" ] }, { "q": "Can I switch from dulaglutide to mazdutide in the US?", "a": "No. Mazdutide is not FDA approved and cannot be lawfully compounded or sold in the United States; it is approved only in China.", "source_ids": [ "fda-503a-bulks", "mazdutide-china-t2d-approval" ] }, { "q": "Which one has heart protection data?", "a": "Only dulaglutide: REWIND showed a 12% relative reduction in major adverse cardiovascular events, and the US label includes that indication. No mazdutide outcomes trial has reported.", "source_ids": [ "rewind", "fda-trulicity-label" ] } ], "sources": [ { "id": "dreams-2", "type": "pubmed", "title": "Guo L et al. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature 2026 (DREAMS-2)", "url": "https://pubmed.ncbi.nlm.nih.gov/41407860/", "pmid": "41407860", "year": 2026 }, { "id": "mazdutide-t2d-phase2", "type": "pubmed", "title": "Zhang B et al. Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. Diabetes Care 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/", "pmid": "37943529", "year": 2024 }, { "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": "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" }, { "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), accessed 2026-09-22", "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 }, { "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" }, { "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-china-obesity-approval", "type": "other", "title": "Manufacturer press release: China's drug regulator (NMPA) approves mazdutide for chronic weight management (June 27, 2025), accessed 2026-09-22", "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": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "dulaglutide-vs-retatrutide", "a": "dulaglutide", "b": "retatrutide", "title": "Dulaglutide vs retatrutide", "summary": "In the phase 2 diabetes trial that tested both, retatrutide 8 mg and 12 mg lowered HbA1c by about 2.0 points versus 1.41 with dulaglutide 1.5 mg at 24 weeks, and cut weight by about 17% versus 2.0% at 36 weeks. Retatrutide is still investigational, however, while dulaglutide is FDA approved with a proven cardiovascular benefit (REWIND).", "verdict": { "winner": "depends", "rationale": "Retatrutide was clearly more effective than dulaglutide in the one direct trial, and its phase 3 program has since reported large weight loss. Dulaglutide is the only one of the two that can be prescribed, has five years of cardiovascular outcomes data, and is approved for children 10 and older. Until retatrutide is approved, the direct result matters for trial participants and for the future, not for a prescription today.", "source_ids": [ "retatrutide-phase2-t2d", "triumph-2-3-topline", "rewind", "fda-trulicity-label", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Dulaglutide 1.5 mg: HbA1c minus 1.41 points at 24 weeks and weight minus 2.0% at 36 weeks.", "b": "Retatrutide: HbA1c minus 1.99 (8 mg slow escalation) and minus 2.02 (12 mg) at 24 weeks, both superior to dulaglutide; weight minus 16.8% to 16.9% at 36 weeks.", "note": "Phase 2, 281 US adults with type 2 diabetes; gastrointestinal adverse events 35% on retatrutide overall and 35% on dulaglutide, ranging from 13% to 50% by retatrutide dose group.", "source_ids": [ "retatrutide-phase2-t2d" ] }, { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist.", "b": "Triple agonist of the GIP, GLP-1, and glucagon receptors.", "source_ids": [ "fda-trulicity-label", "retatrutide-phase2-t2d" ] }, { "name": "Phase 3 evidence", "a": "Large phase 3 program including AWARD-11 (higher doses) and REWIND (cardiovascular outcomes).", "b": "TRANSCEND-T2D-1 (537 adults, 40 weeks) versus placebo; TRIUMPH-2 in obesity with type 2 diabetes reported up to 20.8% weight loss and HbA1c reductions up to 1.6 points at 80 weeks (manufacturer topline).", "source_ids": [ "award-11", "rewind", "transcend-t2d-1", "triumph-2-3-topline" ] }, { "name": "Cardiovascular outcomes", "a": "REWIND hazard ratio 0.88 for major adverse cardiovascular events; labeled indication.", "b": "No cardiovascular outcomes trial has reported. TRIUMPH-3 enrolled adults with established cardiovascular disease but measured weight loss (21.6% to 22.6%).", "source_ids": [ "rewind", "fda-trulicity-label", "triumph-2-3-topline" ] }, { "name": "Regulatory status", "a": "FDA approved (Trulicity, 2014).", "b": "Investigational; not approved by any regulator and not eligible for compounding.", "source_ids": [ "fda-trulicity-label", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Dosing", "a": "Once weekly, 0.75 mg escalated up to 4.5 mg (label).", "b": "Once weekly, 4, 9, or 12 mg in phase 3 trials (no label).", "source_ids": [ "fda-trulicity-label", "transcend-t2d-1" ] } ], "head_to_head_studies": [ { "pmid": "37385280", "title": "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA", "year": 2023, "design": "Randomized, double blind, placebo and active controlled phase 2 trial, 36 weeks", "n": 281, "population": "US adults with type 2 diabetes on diet and exercise or metformin, BMI 25 to 50", "outcome": "HbA1c at 24 weeks minus 2.02 (retatrutide 12 mg) versus minus 1.41 (dulaglutide 1.5 mg); weight at 36 weeks minus 16.94% versus minus 2.02%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/" } ], "faqs": [ { "q": "Did retatrutide beat dulaglutide?", "a": "Yes, in a 281 person phase 2 trial. Retatrutide 8 and 12 mg lowered HbA1c by about 2.0 points versus 1.41 with dulaglutide 1.5 mg at 24 weeks, and weight by about 17% versus 2.0% at 36 weeks.", "source_ids": [ "retatrutide-phase2-t2d" ] }, { "q": "Is retatrutide available instead of dulaglutide?", "a": "No. Retatrutide is not approved by any regulator and cannot lawfully be compounded; it is only available in clinical trials.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Were side effects different?", "a": "Gastrointestinal adverse events occurred in 35% of retatrutide and 35% of dulaglutide participants overall, but rose to 50% in the fastest retatrutide escalation group.", "source_ids": [ "retatrutide-phase2-t2d" ] }, { "q": "Is either drug banned in sport?", "a": "Retatrutide is prohibited under WADA section S0 because it is not approved. Dulaglutide is not on the Prohibited List.", "source_ids": [ "wada-list" ] } ], "sources": [ { "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 randomised, placebo and active-controlled phase 2 trial. Lancet 2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37385280/", "pmid": "37385280", "year": 2023 }, { "id": "triumph-2-3-topline", "type": "other", "title": "Manufacturer press release: retatrutide TRIUMPH-2 and TRIUMPH-3 phase 3 topline results (July 23, 2026), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html", "year": 2026 }, { "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": "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" }, { "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" }, { "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "epitalon-vs-mots-c", "a": "epitalon", "b": "mots-c", "title": "Epitalon vs MOTS-c", "summary": "Epitalon and MOTS-c are tied on the two things that matter most: both have animal only evidence, and both followed the same regulatory path, removed from the FDA Category 2 list on April 15, 2026 and recommended for the 503A bulks list by the Pharmacy Compounding Advisory Committee in July 2026. They differ in what they target. Epitalon is studied for telomeres and life span in cells and mice, mostly by its developing institute; MOTS-c is studied for insulin sensitivity and exercise capacity in mice, with independent human data on blood levels and genetics.", "verdict": { "winner": "depends", "rationale": "Neither wins on evidence grade or regulatory status, because both are animal only and both are awaiting the same final FDA rule after the July 2026 PCAC vote. MOTS-c has the more independent and mechanistically detailed research base (AMPK activation, a human genetic variant linked to diabetes, exercise induced blood levels), which makes it the more defensible research interest for metabolic goals. Epitalon's lifespan data come from one mouse study in which mean life span did not change and from non-randomized human reports of a related extract. Neither should be expected to produce a clinical benefit.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "anisimov-2003", "khavinson-2003-human", "lee-2015", "zempo-2021" ] }, "dimensions": [ { "name": "Structure", "a": "Synthetic tetrapeptide (Ala-Glu-Asp-Gly) modeled on a bovine pineal extract.", "b": "16 amino acid peptide encoded naturally by human mitochondrial DNA.", "source_ids": [ "khavinson-2003-telomerase", "lee-2015" ] }, { "name": "Proposed mechanism", "a": "Induces telomerase (hTERT) and lengthens telomeres in human cell lines; proposed gene regulation and melatonin effects.", "b": "Inhibits the folate cycle, raises AICAR, and activates AMPK, increasing muscle glucose uptake and fat oxidation.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025", "lee-2015" ] }, { "name": "Strongest animal result", "a": "In lifelong female SHR mice, longer life for the longest lived 10% and fewer spontaneous tumors, with no significant change in mean life span.", "b": "Prevented diet induced obesity and insulin resistance, improved insulin sensitivity in aged mice, and improved running capacity in young and old mice.", "source_ids": [ "anisimov-2003", "lee-2015", "reynolds-2021" ] }, { "name": "Human data", "a": "Open, non-randomized reports from the developing institute in elderly patients, mostly using the pineal extract Epithalamin rather than synthetic epitalon.", "b": "Independent observational data: levels rise with exercise in young men; a MOTS-c sequence variant is associated with type 2 diabetes in Japanese men.", "source_ids": [ "khavinson-2003-human", "reynolds-2021", "zempo-2021" ] }, { "name": "Theoretical safety concern", "a": "Telomerase activation could in theory support existing tumors, though mice had fewer tumors.", "b": "Could add to the glucose lowering of diabetes medications, based on mouse data.", "source_ids": [ "anisimov-2003", "lee-2015" ] }, { "name": "Animal study dosing", "a": "0.1 ug per mouse subcutaneously in monthly 5 day courses; Russian human reports used 10 mg courses of the extract.", "b": "0.5 mg/kg per day intraperitoneally (metabolic) up to 15 mg/kg (exercise) in mice.", "note": "No human dose has been established for either peptide.", "source_ids": [ "anisimov-2003", "khavinson-2003-human", "lee-2015", "reynolds-2021" ] }, { "name": "Typical cost through a prescriber", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price. MOTS-c has the same PCAC status as epitalon.", "note": "PCAC's July 2026 recommendation for both is advisory until FDA publishes a final rule.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Are epitalon and MOTS-c legal to get with a prescription?", "a": "Both have the same status. FDA removed each from the 503A Category 2 list on April 15, 2026, and PCAC recommended adding both to the 503A bulks list on July 23 to 24, 2026. FDA had not published a final rule at verification, so state licensed 503A pharmacies vary in whether they will fill them.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Which one has better evidence for longevity?", "a": "Neither has human evidence for longevity. Epitalon extended life only in the longest lived tenth of female mice without changing mean life span, and MOTS-c improved physical capacity in old mice. Human data for both are observational.", "source_ids": [ "anisimov-2003", "reynolds-2021", "khavinson-2003-human" ] }, { "q": "Which is more relevant for blood sugar or weight?", "a": "MOTS-c. It prevented diet induced obesity and insulin resistance in mice, and a human genetic variant that weakens it is associated with type 2 diabetes. Epitalon has not been studied for metabolic outcomes. No human treatment trial exists for either.", "source_ids": [ "lee-2015", "zempo-2021" ] }, { "q": "Are they banned in sport?", "a": "Yes. Both are prohibited at all times: epitalon under WADA section S0 as a non-approved substance, and MOTS-c under section S4.4, where it is named as a metabolic modulator.", "source_ids": [ "wada-list" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 non-approved substances and section S4.4 metabolic modulators)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "epitalon-vs-thymalin", "a": "epitalon", "b": "thymalin", "title": "Epitalon vs thymalin", "summary": "Neither has a randomized human trial, and both trace back to the same St. Petersburg institute, so the real difference is regulatory: epitalon was removed from the FDA Category 2 list in April 2026 and recommended for the 503A bulks list by the Pharmacy Compounding Advisory Committee in July 2026, while thymalin, a calf thymus extract of undefined composition, has no US compounding route at all. Thymalin has slightly more human data (open, non-randomized reports), but neither can currently be lawfully compounded in the United States. Epitalon targets telomeres and aging biology in cell and mouse studies; thymalin is positioned as an immune modulator.", "verdict": { "winner": "depends", "rationale": "Neither has evidence to support clinical use and neither can currently be lawfully compounded; epitalon has a pending PCAC recommendation, which is advisory. Epitalon is a synthetic, defined tetrapeptide, whereas thymalin is a bovine tissue extract of undefined composition with no US nomination. Thymalin's evidence edge (human observational versus animal only) rests on open, non-randomized reports from the developing institute, including the same 2003 elderly cohort study that is cited for Epithalamin.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "khavinson-2003-human", "anisimov-2003", "khavinson-2021" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Animal only. Telomerase activation in human cell lines and a lifelong mouse study; human reports mostly used the pineal extract Epithalamin, not synthetic epitalon.", "b": "Human observational. Open, non-randomized reports in elderly patients and a small open COVID-19 study; no randomized trial or independent replication.", "note": "Both grades rest largely on work from the developing institute.", "source_ids": [ "khavinson-2003-telomerase", "anisimov-2003", "khavinson-2003-human", "khavinson-2021" ] }, { "name": "What it is", "a": "A synthetic tetrapeptide (Ala-Glu-Asp-Gly) with a defined structure, modeled on a bovine pineal extract.", "b": "A mixture of low molecular weight peptides extracted from calf thymus, registered as a drug in Russia.", "note": "A defined molecule can be tested for identity and purity; an extract of undefined composition cannot be fully characterized.", "source_ids": [ "khavinson-2003-telomerase", "khavinson-2020" ] }, { "name": "Proposed mechanism", "a": "Induces telomerase (hTERT) expression and lengthens telomeres in human cell lines; proposed effects on gene expression and melatonin rhythm.", "b": "Short thymic peptides proposed to promote T lymphocyte maturation; activated hematopoietic stem cell differentiation in culture.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025", "khavinson-2020" ] }, { "name": "Main claimed use", "a": "Aging and longevity: in female SHR mice it extended life span of the longest lived 10% and reduced spontaneous tumors, without changing mean life span.", "b": "Immune support: reported fewer infections in elderly patients and faster normalization of inflammatory markers in hospitalized COVID-19 patients.", "source_ids": [ "anisimov-2003", "khavinson-2003-human", "khavinson-2021" ] }, { "name": "Safety concerns", "a": "No systematic human safety data; theoretical concern that telomerase activation could support existing tumors, although mice had fewer tumors.", "b": "No systematic safety data; allergy to bovine protein and theoretical prion or adventitious agent risk from unverified thymus products.", "source_ids": [ "anisimov-2003", "khavinson-2003-human" ] }, { "name": "FDA and compounding status", "a": "Not FDA approved. Removed from the 503A Category 2 list on April 15, 2026; PCAC recommended adding it to the 503A bulks list on July 23 to 24, 2026; no final FDA rule at verification.", "b": "Not FDA approved and not identified on any 503A nomination list or PCAC agenda; as an undefined tissue extract it is not a 503A bulk candidate.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Unclear; not named on the list. Athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "name": "Access and cost", "a": "No lawful compounded channel today: PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory and FDA has not published a final rule.", "b": "No lawful US channel. Prescription drug in Russia and some neighboring countries only.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Human dosing data", "a": "Not established. Mouse studies used 0.1 ug per mouse in monthly courses; Russian human reports used 10 mg intramuscular courses of the extract Epithalamin.", "b": "Not established in indexed literature; Russian labeling describes intramuscular courses with no published dose finding trial.", "source_ids": [ "anisimov-2003", "khavinson-2003-human" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is there any study comparing epitalon and thymalin directly?", "a": "No study compares synthetic epitalon with thymalin. The 2003 Khavinson and Morozov report followed elderly patients given Thymalin, the pineal extract Epithalamin, or both, but it was open and non-randomized, came from the developing institute, and used the extract rather than synthetic epitalon.", "source_ids": [ "khavinson-2003-human" ] }, { "q": "Can I get either one legally in the United States?", "a": "Not today. Epitalon came off FDA Category 2 and PCAC recommended it for the 503A bulks list in 2026, but the recommendation is advisory and FDA had not issued a final rule at verification, so a 503A pharmacy has no federal basis to compound it from bulk. Thymalin has no lawful US route.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Does epitalon lengthen telomeres in people?", "a": "That has not been shown. Telomerase activation and telomere elongation were documented in cultured human cell lines, and the lifespan data come from mice. No human study has measured telomere length after synthetic epitalon.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025", "anisimov-2003" ] }, { "q": "Does thymalin boost the immune system?", "a": "Russian reports describe fewer infections in elderly patients and faster normalization of inflammatory markers in COVID-19 patients, and a cell study showed stem cell differentiation, but none of this was randomized or independently replicated.", "source_ids": [ "khavinson-2003-human", "khavinson-2021", "khavinson-2020" ] }, { "q": "Are they banned in sport?", "a": "Epitalon is prohibited at all times under WADA section S0 as a non-approved substance. Thymalin is not named on the list, so its status is unclear; tested athletes should check with their anti-doping organization before using any unapproved peptide.", "source_ids": [ "wada-list" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "follistatin-344-vs-ace-031", "a": "follistatin-344", "b": "ace-031", "title": "Follistatin-344 vs ACE-031 (ramatercept)", "summary": "ACE-031 has the stronger human evidence: randomized trials showed it increased lean mass and thigh muscle volume, but its Duchenne trial was halted for nosebleeds and dilated blood vessels and development ended in 2011. Injected follistatin-344 has never been tested in people; its human data come from small open label gene therapy trials using a viral vector, not the peptide as sold. Both block myostatin and activin signaling, both are prohibited in sport, and neither has any lawful US source.", "verdict": { "winner": "b", "rationale": "On evidence grade ACE-031 wins: two randomized placebo controlled trials (48 healthy postmenopausal women and 24 boys with Duchenne muscular dystrophy) documented real lean mass gains, while injected follistatin-344 is graded animal only. That same evidence documents ACE-031's harm, since the Duchenne trial stopped early for bleeding and telangiectasia and the program was discontinued. Neither is approved, neither can be compounded, and products sold under either name are unverified, so the win is about what is known, not a recommendation to use it.", "source_ids": [ "attie-2013", "campbell-2017", "mendell-2015", "kota-2009", "fda-503a-bulks" ] }, "dimensions": [ { "name": "What it is", "a": "Recombinant form of the 344 amino acid precursor of follistatin, a natural glycoprotein that binds myostatin, activins, and related ligands.", "b": "Recombinant fusion protein of the activin receptor type IIB extracellular domain and an IgG1 Fc fragment, acting as a ligand trap.", "source_ids": [ "lee-2001", "attie-2013" ] }, { "name": "Mechanism", "a": "Binds myostatin and activin A and B directly and keeps them off activin type II receptors; also binds some bone morphogenetic proteins.", "b": "A soluble decoy receptor that soaks up myostatin, activin A, GDF-11, and other ActRIIB ligands, including ligands that act on blood vessels and red cell production.", "source_ids": [ "lee-2001", "attie-2013", "campbell-2017" ] }, { "name": "Human evidence", "a": "No trial of the injected peptide. Two open label gene therapy trials (AAV1-FS344, 6 patients each) in Becker muscular dystrophy and inclusion body myositis reported better 6 minute walk distance without a placebo group.", "b": "Two randomized placebo controlled trials: a single dose raised lean mass by about 1 kg and thigh muscle volume by about 5% at 29 days in 48 women; in 24 boys with Duchenne muscular dystrophy lean mass rose but walking distance did not improve significantly.", "source_ids": [ "mendell-2015", "mendell-2017", "attie-2013", "campbell-2017" ] }, { "name": "Animal evidence", "a": "Transgenic mice gained 194% to 327% in muscle weight; a single gene therapy injection in macaques increased quadriceps size and strength for 15 months.", "b": "Soluble ActRIIB decoys produced rapid large muscle gains in mice across dystrophy, cachexia, and disuse models, with more bone mass.", "source_ids": [ "lee-2001", "kota-2009", "attie-2013" ] }, { "name": "Key safety findings", "a": "No human safety data for the injected peptide. Fertility hormone suppression is a theoretical concern because follistatin binds activins that regulate FSH; it was not seen in the macaque study.", "b": "Nosebleeds, telangiectasia, gum bleeding, and erythema halted the Duchenne trial; FSH fell in the single dose study.", "source_ids": [ "kota-2009", "campbell-2017", "attie-2013" ] }, { "name": "Development and regulatory status", "a": "Never submitted to FDA and not on any 503A category list; as a biologic sized protein it has no lawful compounding path.", "b": "Investigational biologic whose sponsor ended development in 2011; never nominated for compounding and not a 503A candidate.", "source_ids": [ "fda-503a-bulks", "campbell-2017" ] }, { "name": "Doses in the literature", "a": "None for the peptide. Gene therapy used a single intramuscular series of 6 x 10^11 to 1.2 x 10^12 vector genomes per kg, which does not translate to a peptide dose.", "b": "Single subcutaneous doses of 0.02 to 3 mg/kg in healthy women; 0.5 or 1 mg/kg every 2 to 4 weeks for 12 weeks in boys with Duchenne muscular dystrophy.", "source_ids": [ "mendell-2015", "attie-2013", "campbell-2017" ] }, { "name": "WADA status", "a": "Prohibited at all times under S4; follistatin is named as a myostatin binding protein.", "b": "Prohibited at all times under S4 as a myostatin inhibitor.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which builds more muscle, follistatin-344 or ACE-031?", "a": "Only ACE-031 has been measured in a randomized human trial: a single dose raised lean mass by about 1 kg and thigh muscle volume by about 5% at 29 days. Injected follistatin-344 has no human data; the muscle gains come from transgenic mice, macaque gene therapy, and small open label human gene therapy trials.", "source_ids": [ "attie-2013", "lee-2001", "kota-2009", "mendell-2015" ] }, { "q": "Why was ACE-031 discontinued?", "a": "Its trial in boys with Duchenne muscular dystrophy was stopped early after participants developed nosebleeds, dilated small blood vessels (telangiectasia), and gum bleeding. The ligand trap also blocks signals that maintain blood vessels, and the sponsor ended development in 2011.", "source_ids": [ "campbell-2017" ] }, { "q": "Is the follistatin gene therapy the same as follistatin-344 injections?", "a": "No. The human trials delivered the follistatin gene (AAV1-FS344) into the thigh muscle with a viral vector, so the muscle made its own follistatin. They say nothing about the dose, stability, or safety of injected follistatin-344 peptide sold online.", "source_ids": [ "mendell-2015", "mendell-2017" ] }, { "q": "Can either be prescribed or compounded?", "a": "No. Neither is FDA approved, neither is on the 503A bulks list or any 503A category list, and both are large recombinant proteins rather than small peptides. Products sold under either name are research chemicals that are not lawful for human use.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Are they banned in sport?", "a": "Yes. Myostatin inhibitors, including follistatin and ActRIIB ligand traps, are prohibited at all times under S4 of the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "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": "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": "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "ghrp-2-vs-ghrp-6", "a": "ghrp-2", "b": "ghrp-6", "title": "GHRP-2 vs GHRP-6", "summary": "GHRP-2 and GHRP-6 are closely related six amino acid ghrelin receptor agonists that release growth hormone, cortisol, and prolactin and increase hunger. GHRP-2 has the edge on evidence and real world use: it is approved in Japan (as pralmorelin) as a diagnostic test for growth hormone deficiency, while GHRP-6, the original compound from 1984, has only acute pharmacology studies. Neither has any approved therapeutic use, both are in FDA's 503B Category 2 with no 503A pathway, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "Both carry the human_observational grade and the same not_eligible US status, so the edge is narrow. GHRP-2 has a regulator approved diagnostic use outside the US and a validated adult diagnostic protocol (Chihara 2007), plus a controlled crossover quantifying its appetite effect; GHRP-6 has only small acute studies. Neither has a randomized trial of repeated therapeutic use, and FDA cited glucose, cortisol, and immunogenicity concerns for both.", "source_ids": [ "chihara-2007", "laferrere-2005", "frieboes-1995", "fda-category-2" ] }, "dimensions": [ { "name": "Origin and structure", "a": "D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2; contains the unnatural amino acid D-beta-naphthylalanine, which FDA noted complicates characterization.", "b": "His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; the first GHRP, described in 1984 and the template for GHRP-2, hexarelin, and ipamorelin.", "source_ids": [ "bowers-1998", "bowers-1984", "fda-category-2" ] }, { "name": "Best human evidence", "a": "Diagnostic validation: a 100 ug intravenous test with a peak GH cutoff of 9 ng/mL identified severe adult GH deficiency (62 patients plus controls). Pediatric dose response in 34 short children.", "b": "Acute studies only: four overnight 50 ug intravenous boluses raised GH, ACTH, cortisol, and stage 2 sleep in healthy men; oral 300 ug/kg released GH in short children.", "source_ids": [ "chihara-2007", "pihoker-1995", "frieboes-1995", "bellone-1995" ] }, { "name": "Approved uses anywhere", "a": "Approved in Japan as pralmorelin, a diagnostic agent for GH deficiency. No therapeutic approval anywhere.", "b": "Never approved for any use in any country.", "source_ids": [ "chihara-2007", "fda-category-2" ] }, { "name": "Appetite effect", "a": "A 1 ug/kg per hour infusion raised ad libitum food intake by 35.9% versus saline in a double blind crossover of 7 healthy men.", "b": "Marked hunger is its most consistently reported effect, but no controlled human food intake study is in the record.", "source_ids": [ "laferrere-2005", "camanni-1998" ] }, { "name": "Other hormonal effects", "a": "Raises prolactin, ACTH, and cortisol alongside GH; in healthy adults it released more GH than GHRH.", "b": "Raises ACTH, cortisol, and prolactin; GH release is synergistic with GHRH.", "source_ids": [ "arvat-1997", "frieboes-1995", "camanni-1998" ] }, { "name": "Studied routes and doses", "a": "Intravenous 1 ug/kg (children) or 100 ug (adults) as a diagnostic bolus; intranasal in research. No chronic dose established.", "b": "Intravenous 1 ug/kg or 4 x 50 ug overnight; oral 300 ug/kg in children. No chronic dose established.", "source_ids": [ "pihoker-1995", "chihara-2007", "frieboes-1995", "bellone-1995" ] }, { "name": "FDA Category 2 rationale", "a": "503B Category 2 (injectable and nasal routes) since September 29, 2023: immunogenicity, characterization problems from the unnatural amino acid, and reports of serious adverse events including pancreatitis in critically ill subjects.", "b": "503B Category 2 since September 29, 2023: immunogenicity from aggregation and impurities, cortisol effects, and higher blood glucose from reduced insulin sensitivity.", "note": "Neither has a 503A nomination or listing, so no licensed pharmacy can compound either. Both are prohibited under WADA section S2.", "source_ids": [ "fda-category-2", "fda-503a-bulks", "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "What is the difference between GHRP-2 and GHRP-6?", "a": "Both are six amino acid ghrelin receptor agonists. GHRP-6 was the first, described in 1984; GHRP-2 is a later analog that became a licensed diagnostic agent in Japan. Both raise GH, cortisol, and prolactin and increase appetite.", "source_ids": [ "bowers-1984", "bowers-1998", "chihara-2007", "camanni-1998" ] }, { "q": "Which one makes you hungrier?", "a": "GHRP-6 is the one most associated with hunger in reviews of the class, but the only controlled human measurement is for GHRP-2, which raised food intake by 35.9% in healthy men. No trial has compared them directly.", "source_ids": [ "camanni-1998", "laferrere-2005" ] }, { "q": "Has either been approved as a medicine?", "a": "GHRP-2 is approved in Japan only as a diagnostic test for growth hormone deficiency. GHRP-6 has never been approved. Neither has an approved therapeutic use anywhere.", "source_ids": [ "chihara-2007", "fda-category-2" ] }, { "q": "Can a US pharmacy compound GHRP-2 or GHRP-6?", "a": "No. FDA placed both in 503B Category 2 in September 2023 and neither has a 503A nomination or listing, so there is no lawful compounding pathway. Research chemical products are not lawful for human use.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are growth hormone secretagogues prohibited at all times under WADA section S2, and anti-doping labs test for their urinary metabolites.", "source_ids": [ "wada-list", "semenistaya-2015" ] } ], "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": "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": "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-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" }, { "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" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "glutathione-vs-nad-plus", "a": "glutathione", "b": "nad-plus", "title": "Glutathione vs NAD+", "summary": "Glutathione and NAD+ sit at the same evidence and regulatory level: small randomized trials show oral forms raise body levels, no trial shows a clinical outcome, and the injectable forms clinics sell are compounded from nominated bulk substances awaiting an FDA decision. The choice depends on the goal. Oral glutathione raised body glutathione stores and natural killer cell activity over 6 months, while oral NAD+ precursors raised blood NAD+ and, in one trial, improved muscle insulin sensitivity.", "verdict": { "winner": "depends", "rationale": "Both are graded human RCT on the strength of oral supplement trials, both injectables are compounded under FDA's interim policy for nominated bulk substances, and neither is a prohibited substance in sport. NAD+ precursors have the one metabolic finding (about 25% better muscle insulin sensitivity with NMN in 25 prediabetic women), while glutathione has the longer trial (6 months, 54 adults) showing sustained increases in body stores and immune cell activity. For intravenous use of either, there is no randomized evidence of benefit, and FDA has warned about endotoxin contamination in compounded glutathione.", "source_ids": [ "richie-2015", "allen-2011", "yoshino-2021", "martens-2018", "grant-2019", "fda-503a-bulks", "fda-compounding-qa" ] }, "dimensions": [ { "name": "What it is", "a": "A tripeptide (glutamate, cysteine, glycine) and the main intracellular antioxidant.", "b": "A coenzyme (a dinucleotide, not a peptide) for energy metabolism and a substrate for sirtuins, PARP, and CD38.", "source_ids": [ "richie-2015", "rajman-2018" ] }, { "name": "Main randomized trial result", "a": "Oral 1,000 mg per day for 6 months raised whole blood glutathione about 30% and lymphocyte glutathione about 35%, and doubled natural killer cell activity at 3 months (54 adults). A 4 week trial of 500 mg twice daily found no change.", "b": "NR 1,000 mg per day raised blood NAD+ about 60% in 24 older adults; NMN 250 mg per day improved muscle insulin sensitivity about 25% in 25 prediabetic women, without changes in weight or fasting glucose.", "source_ids": [ "richie-2015", "allen-2011", "martens-2018", "yoshino-2021" ] }, { "name": "Negative or null findings", "a": "No change in oxidative stress biomarkers in the 4 week trial; skin lightening trials are small and inconsistent.", "b": "A 2025 meta-analysis found no effect of NR or NMN on muscle mass or physical function.", "source_ids": [ "allen-2011", "prokopidis-2025" ] }, { "name": "Intravenous evidence", "a": "No published randomized trial of IV glutathione for any common clinic indication.", "b": "One 11 person pharmacokinetic pilot of a 6 hour infusion with no clinical endpoints; plasma NAD+ lagged and metabolites were excreted in urine.", "source_ids": [ "richie-2015", "grant-2019" ] }, { "name": "Safety signals", "a": "Oral forms well tolerated; FDA has warned about compounded injectable glutathione with high endotoxin causing fever and chills, and about injections marketed for skin lightening.", "b": "Oral precursors well tolerated; IV infusions commonly cause chest pressure, nausea, cramping, and flushing when run quickly.", "source_ids": [ "fda-compounding-qa", "richie-2015", "martens-2018", "grant-2019" ] }, { "name": "Regulatory status", "a": "Oral: dietary supplement. Injectable: nominated 503A bulk substance compounded under FDA's interim enforcement policy where state boards permit.", "b": "Oral NR and NMN: dietary supplements (FDA has questioned NMN's status as a dietary ingredient). Injectable: nominated 503A bulk substance compounded under the same interim policy.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa" ] }, { "name": "Theoretical interactions", "a": "May blunt chemotherapy that works through oxidative stress; oncology patients need their oncologist's input.", "b": "Is the substrate of PARP inhibitors used in oncology; the interaction has not been tested.", "source_ids": [ "richie-2015", "rajman-2018" ] }, { "name": "Typical cost", "a": "Oral roughly 20 to 50 USD per month; IV 100 to 300 USD per infusion; compounded injections roughly 100 to 250 USD per month.", "b": "Oral NR or NMN roughly 30 to 100 USD per month; IV 300 to 1,000 USD per session; compounded injections roughly 150 to 400 USD per month.", "source_ids": [ "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Should I take glutathione or NAD+?", "a": "It depends on the goal, and neither has proven clinical benefits. Oral glutathione raised body glutathione and natural killer cell activity over 6 months. Oral NAD+ precursors raised blood NAD+, and NMN improved muscle insulin sensitivity in prediabetic women. Neither trial measured symptoms, disease, or aging outcomes.", "source_ids": [ "richie-2015", "martens-2018", "yoshino-2021" ] }, { "q": "Are IV drips of either one proven?", "a": "No. There is no randomized trial of IV glutathione for common clinic uses, and the only IV NAD+ study was an 11 person pharmacokinetic pilot without clinical endpoints. The randomized evidence for both is for oral forms.", "source_ids": [ "grant-2019", "richie-2015" ] }, { "q": "Does oral glutathione get absorbed?", "a": "The 6 month trial found that daily oral glutathione raised levels in blood, red cells, lymphocytes, and buccal cells in a dose dependent way, but a 4 week trial found no change, so sustained dosing appears necessary. Levels returned to baseline within a month of stopping.", "source_ids": [ "richie-2015", "allen-2011" ] }, { "q": "Are compounded glutathione and NAD+ injections legal?", "a": "Both are nominated bulk substances that 503A pharmacies may compound under FDA's interim enforcement policy where state boards allow, pending FDA's final decision. FDA has warned about endotoxin contamination in some compounded glutathione products.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa" ] }, { "q": "Can athletes use them?", "a": "Neither substance is prohibited, but WADA method M2 prohibits intravenous infusions or injections above 100 mL per 12 hour period outside legitimate hospital care, which can apply to IV drips of either.", "source_ids": [ "wada-list" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (including section M2 on intravenous infusions)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "hcg-vs-gonadorelin", "a": "hcg", "b": "gonadorelin", "title": "HCG vs gonadorelin", "summary": "hCG has the stronger evidence and the only regimen that matches how these drugs are actually used alongside testosterone therapy: it acts directly on the testis, lasts 24 to 36 hours per dose, and a retrospective series of 26 men on testosterone found that 500 IU every other day preserved semen parameters. Gonadorelin is native GnRH with a half-life of minutes, and its evidence is for pulsatile pump delivery, not the 2 to 3 times weekly injections sold by telehealth clinics, which have never been studied. Gonadorelin's one advantage is access: since hCG became a biologic in March 2020 it can no longer be compounded, while gonadorelin can.", "verdict": { "winner": "a", "rationale": "hCG wins on evidence grade (human RCT, FDA approved as Pregnyl, Novarel, and Ovidrel with label indications for hypogonadotropic hypogonadism and ovulation induction) and on the fit between its pharmacology and intermittent dosing. In the only direct comparison, a 42 patient series in hypogonadotropic men, hCG plus hMG and pulsatile GnRH induced sperm equally well, but that GnRH arm used a pump delivering pulses every 2 hours. Compounded gonadorelin injected 2 to 3 times a week has no published study, so its lower cost and compounding eligibility buy a regimen without evidence. Choose gonadorelin only when brand hCG is unaffordable and the prescriber accepts that the regimen is unstudied.", "source_ids": [ "hsieh-2013", "buchter-1998", "amory-2008", "pregnyl-label", "fda-compounding-qa", "tranoulis-2018" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Human RCT. Standard of care for ovulation triggering and for inducing puberty and fertility in hypogonadotropic men, with label evidence and a prospective dose ranging study showing hCG maintains intratesticular testosterone in gonadotropin suppressed men.", "b": "Human observational. A 2018 meta-analysis of 35 studies (1,002 women) of pulsatile GnRH in hypothalamic amenorrhea and a 42 patient series in hypogonadotropic men, all with pump delivery.", "source_ids": [ "amory-2008", "pregnyl-label", "tranoulis-2018", "buchter-1998" ] }, { "name": "Direct comparison", "a": "hCG plus hMG in 42 men with hypogonadotropic hypogonadism: sperm induced in most treatment courses, pregnancies in 26 of 36 courses overall, no significant difference from pulsatile GnRH.", "b": "Pulsatile GnRH by pump in the same series: testicular volume doubled within 5 to 12 months and outcomes matched hCG plus hMG.", "note": "This is a single center case series, not a randomized trial, and the GnRH arm used a portable pump delivering pulses every 2 hours.", "source_ids": [ "buchter-1998" ] }, { "name": "Mechanism", "a": "Binds the LH receptor on testicular Leydig cells (and ovarian theca and granulosa cells) directly, driving intratesticular testosterone even when pituitary LH is suppressed by exogenous testosterone.", "b": "Binds GnRH receptors on the pituitary to release LH and FSH. Works only if the pituitary is responsive, and continuous or high frequency exposure suppresses rather than stimulates gonadotropins.", "source_ids": [ "amory-2008", "dwyer-2024" ] }, { "name": "Half-life and dosing frequency", "a": "About 24 to 36 hours, which is why labels dose 2 to 3 times per week (for example 500 to 1,000 units three times weekly) and the testosterone adjunct series used 500 IU every other day.", "b": "About 2 to 4 minutes. Evidence based use is pulses every 60 to 120 minutes by pump, or a single 100 mcg diagnostic dose. No literature dosing exists for injections 2 to 3 times per week.", "source_ids": [ "pregnyl-label", "hsieh-2013", "tranoulis-2018", "drugs-at-fda" ] }, { "name": "Evidence as a testosterone therapy adjunct", "a": "Retrospective review of 26 hypogonadal men on testosterone given 500 IU hCG intramuscularly every other day: serum testosterone rose from 207 to 1,056 ng/dL, semen parameters were unchanged over more than a year, no patient became azoospermic, and 9 of 26 contributed to a pregnancy.", "b": "No published study of gonadorelin as an adjunct to testosterone therapy in any dosing schedule.", "source_ids": [ "hsieh-2013", "dwyer-2024" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (Pregnyl, Novarel, Ovidrel). Transitioned to biologic status on March 23, 2020, and FDA states biological products are not eligible for the 503A or 503B compounding exemptions, so compounded hCG is unlawful.", "b": "Active ingredient of two discontinued FDA approved products (Factrel, Lutrepulse), so a 503A pharmacy can compound it under a prescription. As a 10 amino acid peptide it was unaffected by the 2020 biologic transition. Not on the Category 2 list.", "source_ids": [ "fda-compounding-qa", "pregnyl-label", "drugs-at-fda", "fda-cat2" ] }, { "name": "Typical cost", "a": "Brand hCG roughly 100 to 300 USD per 10,000 unit vial, which at 500 IU three times a week lasts about 6 to 7 weeks; Ovidrel prefilled syringes roughly 150 to 250 USD each.", "b": "Compounded gonadorelin through telehealth testosterone clinics typically 50 to 150 USD per month.", "note": "Prices verified on the last verified date and change often.", "source_ids": [ "pregnyl-label", "fda-compounding-qa" ] }, { "name": "Side effects", "a": "Headache, irritability, fatigue, edema, gynecomastia and breast tenderness from rising estradiol, acne, injection site pain, rare thromboembolism, ovarian hyperstimulation in women, and interference with pregnancy tests and hCG tumor marker assays.", "b": "Injection site reactions, headache, nausea, flushing, rare hypersensitivity including anaphylaxis, antibody formation with prolonged use, and paradoxical LH and FSH suppression if given continuously.", "source_ids": [ "pregnyl-label", "novarel-label", "drugs-at-fda", "tranoulis-2018" ] }, { "name": "WADA status", "a": "Prohibited in male athletes under S2 (chorionic gonadotropin).", "b": "Prohibited in male athletes under S2 (GnRH and its analogs).", "note": "Both are listed in the same section; neither is a lawful choice for a tested male athlete.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [ { "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 comparing pulsatile GnRH with hCG plus hMG", "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/" } ], "faqs": [ { "q": "Why did clinics switch from hCG to gonadorelin?", "a": "Because of regulation, not evidence. On March 23, 2020 hCG products transitioned to biologics license applications, and FDA states biological products cannot be compounded under sections 503A or 503B. Gonadorelin is a small peptide that was the active ingredient of approved drugs, so it remained eligible for compounding and filled the gap.", "source_ids": [ "fda-compounding-qa", "drugs-at-fda" ] }, { "q": "Does gonadorelin work the same way as hCG for keeping the testes active on testosterone?", "a": "No. hCG acts directly on the LH receptor in the testis and lasts more than a day per dose, which is why a series of 26 men on testosterone kept normal semen parameters on 500 IU every other day. Gonadorelin acts on the pituitary, lasts minutes, and only sustains gonadotropins when delivered in pulses by pump. There is no study of the intermittent injections clinics prescribe.", "source_ids": [ "hsieh-2013", "amory-2008", "tranoulis-2018", "dwyer-2024" ] }, { "q": "Which is better for inducing sperm in men with hypogonadotropic hypogonadism?", "a": "They performed equally in the only direct comparison, a 42 patient series in which pulsatile GnRH and hCG plus hMG each induced sperm in most treatment courses. The difference is practical: GnRH requires a portable pump delivering pulses around the clock, while hCG is injected 2 to 3 times per week.", "source_ids": [ "buchter-1998", "pregnyl-label" ] }, { "q": "Is hCG useful for weight loss, and is gonadorelin?", "a": "Neither. A criteria-based meta-analysis of 24 trials found no evidence that hCG causes weight loss, fat redistribution, or reduced hunger, the Pregnyl label says it has not been shown to be effective for obesity, and FDA has warned that hCG diet products are illegal. Gonadorelin has no weight related data at all.", "source_ids": [ "lijesen-1995", "pregnyl-label", "fda-hcg-diet" ] }, { "q": "Can I still get brand hCG through a telehealth clinic?", "a": "Yes. Telehealth clinics can prescribe Pregnyl, Novarel, or Ovidrel to be filled at a retail or specialty pharmacy; what they cannot lawfully supply is compounded hCG. Brand vials cost roughly 100 to 300 USD per 10,000 units, versus 50 to 150 USD per month for compounded gonadorelin.", "source_ids": [ "pregnyl-label", "fda-compounding-qa" ] } ], "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": "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": "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": "pregnyl-label", "type": "fda", "title": "FDA prescribing information for Pregnyl (chorionic gonadotropin for injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pregnyl", "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/search.cfm?labeltype=all&query=novarel", "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": "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-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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "hcg-vs-kisspeptin-10", "a": "hcg", "b": "kisspeptin-10", "title": "HCG vs kisspeptin-10", "summary": "hCG is the evidence-backed option: it is FDA approved as Pregnyl, Novarel, and Ovidrel, it has decades of trial and label evidence for male hypogonadotropic hypogonadism and ovulation induction, and a retrospective series showed it preserves semen parameters in men on testosterone. Kisspeptin-10 acts one step higher in the same axis and raises LH and testosterone in small physiology studies of healthy volunteers, but no study has tested it for a clinical endpoint and it sits on the FDA Category 2 list. Neither is a legal option through compounding: hCG because it became a biologic in 2020, kisspeptin-10 because of its Category 2 listing.", "verdict": { "winner": "a", "rationale": "hCG wins on evidence grade (human RCT and label evidence versus human physiology studies only) and on regulatory status (an FDA approved biologic available by prescription versus a Category 2 substance with no lawful route for human use). Kisspeptin-10 is scientifically interesting because it works upstream through the patient's own GnRH pulses, but the only chronic human data are 12 days of hormone measurements in 15 healthy men, and the one randomized trial in patients used kisspeptin-54, not kisspeptin-10.", "source_ids": [ "pregnyl-label", "hsieh-2013", "buchter-1998", "yeung-2026", "mills-2023", "fda-cat2", "fda-compounding-qa" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Human RCT. Standard of care for ovulation triggering and for inducing puberty and fertility in hypogonadotropic men; sperm induced in 54 of 57 treatment courses in a 42 patient series.", "b": "Human observational. Physiology studies in groups of 4 to 15 healthy volunteers measuring LH, FSH, and testosterone; no study of a clinical endpoint.", "note": "The 2026 randomized study of kisspeptin-10 measured hormone levels in healthy men, so it does not establish clinical benefit.", "source_ids": [ "pregnyl-label", "buchter-1998", "jayasena-2011", "yeung-2026" ] }, { "name": "Mechanism", "a": "Binds the LH receptor directly on Leydig cells (men) and theca and granulosa cells (women), bypassing the hypothalamus and pituitary.", "b": "Binds KISS1R on hypothalamic GnRH neurons, triggering the patient's own GnRH pulses and then pituitary LH and FSH release.", "note": "Because kisspeptin-10 works upstream, it depends on an intact pituitary; hCG works even when pituitary LH is suppressed.", "source_ids": [ "pregnyl-label", "jayasena-2015", "jayasena-2011" ] }, { "name": "Use alongside testosterone therapy", "a": "Retrospective series of 26 men on testosterone given 500 IU every other day: no decline in semen parameters, no azoospermia, and 9 contributed to a pregnancy.", "b": "Not studied in men on testosterone therapy.", "source_ids": [ "hsieh-2013", "yeung-2026" ] }, { "name": "Half-life and dosing pattern", "a": "Long half-life of about 24 to 36 hours allows injections 2 to 3 times per week (label schedules for hypogonadotropic hypogonadism).", "b": "Half-life of minutes; research protocols used intravenous boluses or subcutaneous pump infusions, and continuous infusion lost its effect while 8 hour daily infusions sustained it for 12 days.", "source_ids": [ "pregnyl-label", "novarel-label", "yeung-2026" ] }, { "name": "Side effects", "a": "Headache, edema, gynecomastia from rising estradiol, acne, injection site reactions; ovarian hyperstimulation and multiple pregnancy in women; rare thromboembolism.", "b": "No adverse effects reported in short research protocols; no long-term human safety data; FDA cites immunogenicity and impurity concerns for compounded product.", "source_ids": [ "pregnyl-label", "jayasena-2011", "fda-cat2" ] }, { "name": "FDA and compounding status", "a": "FDA approved (Pregnyl, Novarel, Ovidrel). Transitioned to a biologic on March 23, 2020, so compounded hCG is no longer lawful under 503A or 503B.", "b": "Not FDA approved. Placed on the 503A Category 2 list on September 29, 2023; a 503A pharmacy may not compound it.", "source_ids": [ "fda-compounding-qa", "pregnyl-label", "fda-cat2" ] }, { "name": "WADA status", "a": "Prohibited under S2 for male athletes.", "b": "Prohibited (S0 and S2 as a gonadotropin releasing agent without approval).", "note": "Both are banned in tested sport, but on different grounds: hCG as a named S2 hormone in men, kisspeptin-10 as an unapproved substance and releasing factor.", "source_ids": [ "wada-list" ] }, { "name": "Access path and cost", "a": "Prescription filled at a retail or specialty pharmacy; brand vials roughly 100 to 300 USD per 10,000 units, lasting about 6 to 7 weeks at 500 IU three times weekly.", "b": "No lawful access outside a clinical trial. Products sold as research chemicals are not lawful for human use and are not verified for purity.", "source_ids": [ "pregnyl-label", "novarel-label", "fda-cat2" ] }, { "name": "Weight loss claims", "a": "Label states hCG is not effective adjunctive therapy for obesity; a meta-analysis of 24 trials found no benefit, and FDA calls over the counter hCG diet products illegal.", "b": "No weight loss claims or studies.", "source_ids": [ "lijesen-1995", "fda-hcg-diet", "pregnyl-label" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Can kisspeptin-10 replace hCG for men on testosterone?", "a": "There is no evidence that it can. hCG has a retrospective series showing preserved semen parameters in men on testosterone, while kisspeptin-10 has only been studied in healthy men not taking testosterone, for up to 12 days, with hormone levels as the endpoint. Kisspeptin-10 also requires a responsive pituitary, which exogenous testosterone suppresses.", "source_ids": [ "hsieh-2013", "yeung-2026", "jayasena-2011" ] }, { "q": "Which is legal to get in the United States?", "a": "Only hCG, and only as brand Pregnyl, Novarel, or Ovidrel by prescription. Compounded hCG became unlawful when it transitioned to a biologic in 2020, and kisspeptin-10 has been on the FDA Category 2 list since September 2023, so no pharmacy may compound it.", "source_ids": [ "fda-compounding-qa", "fda-cat2", "pregnyl-label" ] }, { "q": "Why would anyone use kisspeptin-10 instead of hCG?", "a": "The theoretical appeal is that kisspeptin-10 stimulates the body's own GnRH, LH, and FSH rather than replacing LH, and research groups study kisspeptins for fertility and sexual desire. In practice the human data are hormone measurements in small groups of healthy volunteers, and the randomized trial on sexual desire used kisspeptin-54.", "source_ids": [ "jayasena-2015", "yeung-2026", "mills-2023" ] }, { "q": "Are both banned in sport?", "a": "Yes. hCG is prohibited in male athletes under section S2 of the WADA Prohibited List, and kisspeptin-10 is prohibited as an unapproved substance that stimulates gonadotropin release.", "source_ids": [ "wada-list" ] }, { "q": "Does either help with weight loss?", "a": "No. The hCG label says it has not been shown to be effective for obesity, a meta-analysis of 24 trials found no benefit, and FDA warns that over the counter hCG diet products are illegal. Kisspeptin-10 has not been studied for weight loss.", "source_ids": [ "pregnyl-label", "lijesen-1995", "fda-hcg-diet" ] } ], "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": "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": "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": "pregnyl-label", "type": "fda", "title": "FDA prescribing information for Pregnyl (chorionic gonadotropin for injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pregnyl" }, { "id": "novarel-label", "type": "fda", "title": "FDA prescribing information for Novarel (chorionic gonadotropin for injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=novarel" }, { "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, sections S0 and S2", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "hexarelin-vs-ghrp-2", "a": "hexarelin", "b": "ghrp-2", "title": "Hexarelin vs GHRP-2", "summary": "Hexarelin and GHRP-2 are sibling synthetic hexapeptides that release growth hormone through the ghrelin receptor, and the one direct comparison in healthy adults found both released more GH than GHRH while also raising prolactin, ACTH, and cortisol. GHRP-2 has the more useful human record because it is approved in Japan as a diagnostic test for growth hormone deficiency and studied in a placebo controlled crossover, but FDA placed it in 503B Category 2 in 2023 citing adverse event reports, while hexarelin was never nominated for compounding at all and its only chronic study showed the GH response fading by about half over 16 weeks. Neither has a lawful access path in the United States and both are prohibited by WADA at all times.", "verdict": { "winner": "depends", "rationale": "If the question is which peptide has the better documented human pharmacology, GHRP-2 wins: a validated 100 ug intravenous diagnostic test in 62 adults, a dose response study in 34 children, and a placebo controlled crossover in healthy men. If the question is which one a person could use as a therapy, neither: hexarelin's only long term study found the GH response attenuated by about 50% with no sustained IGF-1 rise, GHRP-2 has no chronic therapeutic trial and sits in FDA's 503B Category 2 for immunogenicity and adverse event concerns, and both are unscheduled for 503A compounding, unapproved, and WADA prohibited under S2.", "source_ids": [ "arvat-1997", "rahim-1998", "chihara-2007", "laferrere-2005", "fda-category-2", "fda-503a-bulks", "wada-list" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "In a crossover study of healthy young adults, hexarelin released more GH than GHRH and raised prolactin, ACTH, and cortisol.", "b": "In the same study GHRP-2 also released more GH than GHRH with the same rise in prolactin, ACTH, and cortisol; the two peptides behaved similarly as acute GH stimuli.", "note": "Arvat 1997 is a single dose pharmacology study, not a therapeutic trial. It establishes that the two peptides are pharmacologically interchangeable as acute GH releasers and says nothing about chronic use.", "source_ids": [ "arvat-1997" ] }, { "name": "Evidence grade", "a": "Human observational. Acute dose finding in healthy adults by intravenous, subcutaneous, intranasal, and oral routes (Ghigo 1994), a 16 week open treatment study (Rahim 1998), a sleep laboratory study, and a single dose cardiac surgery study. No randomized trial of a clinical outcome.", "b": "Human observational. Dose response in 34 short children (Pihoker 1995), a diagnostic validation study in 62 adults (Chihara 2007), and a double blind placebo controlled crossover of appetite in 7 healthy men (Laferrere 2005). The crossover is randomized but is a single dose physiology study, so it does not raise the grade.", "source_ids": [ "ghigo-1994", "rahim-1998", "pihoker-1995", "chihara-2007", "laferrere-2005" ] }, { "name": "Chronic use data", "a": "The only chronic human study: 1.5 mg subcutaneously twice daily for 16 weeks in healthy adults. The GH response to hexarelin fell by about half, IGF-1 did not rise durably, and the response recovered after washout.", "b": "No chronic therapeutic study in adults has been published. All human dosing is single intravenous doses or a short infusion; the subcutaneous regimens sold online come from no trial.", "note": "Hexarelin's attenuation is the clearest evidence that continuous ghrelin receptor stimulation is self limiting; GHRP-2 has simply never been tested long enough to show whether the same happens.", "source_ids": [ "rahim-1998", "chihara-2007" ] }, { "name": "Structure and mechanism", "a": "Methylated analog of GHRP-6 (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2). Activates GHS-R1a and also binds CD36 on cardiac and vascular cells, the basis of rodent cardioprotection data and a single human bypass surgery study.", "b": "D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2, containing an unnatural naphthylalanine residue. Activates GHS-R1a; FDA cited the unnatural amino acid as complicating characterization. No CD36 or cardiac data.", "source_ids": [ "camanni-1998", "bowers-1998", "broglio-2002", "fda-category-2" ] }, { "name": "Side effects seen in studies", "a": "Rise in cortisol, ACTH, and prolactin with each dose; transient flushing after intravenous dosing; reduced slow wave sleep in a placebo controlled sleep study; increased hunger.", "b": "Rise in cortisol and prolactin; a 35.9% increase in ad libitum food intake in the placebo controlled crossover; flushing and sweating after intravenous dosing. FDA additionally cites reports of increased insulin requirements, pancreatitis, infection, and death in critically ill study subjects without established causality.", "source_ids": [ "arvat-1997", "frieboes-2004", "laferrere-2005", "fda-category-2" ] }, { "name": "Regulatory status", "a": "Unscheduled. Never approved anywhere, never nominated for the 503A or 503B bulks lists, and absent from Category 2. There is no lawful basis for a compounding pharmacy to use it.", "b": "Not eligible. FDA placed GHRP-2 (injectable and nasal routes) in 503B Category 2 on September 29, 2023 and it remained there as of April 22, 2026; it has no 503A nomination. Pralmorelin is approved in Japan only as a diagnostic agent.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S2 as a growth hormone secretagogue.", "b": "Prohibited at all times under section S2; GHRP-2 is one of the GHRPs named on the list.", "source_ids": [ "wada-list" ] }, { "name": "Routes studied", "a": "Intravenous, subcutaneous, intranasal, and oral all produced GH release in the 1994 dose finding study, with intravenous 1 to 2 ug/kg producing the largest response.", "b": "Intravenous bolus and infusion in the diagnostic and physiology studies; intranasal in children. Subcutaneous use as sold has no published human data.", "source_ids": [ "ghigo-1994", "pihoker-1995", "chihara-2007" ] }, { "name": "Cost and access", "a": "No licensed channel; hexarelin was never nominated for the 503A bulks list. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "b": "No licensed channel; GHRP-2 is in FDA's 503B Category 2. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] } ], "head_to_head_studies": [ { "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 of single doses in healthy volunteers", "population": "Healthy young adults", "outcome": "Both peptides released more GH than GHRH and raised prolactin, ACTH, and cortisol; no meaningful difference between hexarelin and GHRP-2 as acute stimuli", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/9285939/" } ], "faqs": [ { "q": "Which releases more growth hormone, hexarelin or GHRP-2?", "a": "In the one direct comparison, both released more GH than GHRH after a single dose and the two were similar to each other. Hexarelin is often described as the more potent of the GHRP family, but the human crossover did not show a clinically meaningful gap, and in hexarelin's only chronic study the GH response fell by about half over 16 weeks.", "source_ids": [ "arvat-1997", "rahim-1998" ] }, { "q": "Is either one legal to get from a compounding pharmacy in the United States?", "a": "No. Hexarelin has never been nominated for the FDA bulks lists, so no pharmacy has a basis to compound it. GHRP-2 was placed in 503B Category 2 in September 2023 and has no 503A listing, which means neither 503A pharmacies nor 503B outsourcing facilities can lawfully compound it.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Do they raise cortisol and prolactin?", "a": "Yes, both do with every dose. The crossover study found both hexarelin and GHRP-2 raised prolactin, ACTH, and cortisol alongside GH, which is a class effect of ghrelin receptor agonists that the GHRH analogs do not share.", "source_ids": [ "arvat-1997" ] }, { "q": "Which one increases appetite more?", "a": "Both are ghrelin mimetics and both increase hunger. GHRP-2 has the measured number: a 1 ug/kg per hour infusion raised ad libitum food intake by 35.9% in a placebo controlled crossover in healthy men. Hexarelin's hunger effect is reported but was not quantified in a controlled feeding study.", "source_ids": [ "laferrere-2005", "ghigo-1994" ] }, { "q": "Can athletes use either?", "a": "No. Both are growth hormone secretagogues prohibited at all times under WADA section S2, in and out of competition.", "source_ids": [ "wada-list" ] }, { "q": "Does GHRP-2 have any approved use anywhere?", "a": "Only as a diagnostic. Pralmorelin (GHRP-2) is approved in Japan for testing growth hormone deficiency, where a 100 ug intravenous dose with a peak GH cutoff of 9 ng/mL separates severe adult GH deficiency from normal secretion. Hexarelin has no approved use in any country.", "source_ids": [ "chihara-2007", "fda-category-2" ] } ], "sources": [ { "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": "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": "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": "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": "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "igf-1-lr3-vs-peg-mgf", "a": "igf-1-lr3", "b": "peg-mgf", "title": "IGF-1 LR3 vs PEG-MGF", "summary": "Neither IGF-1 LR3 nor PEG-MGF has ever been given to people in a published study, neither has a lawful US source, and both are prohibited in sport. IGF-1 LR3 at least has characterized pharmacology, with rat studies showing it is about 2.5 fold more anabolic than native IGF-1, and its risks can be inferred from approved IGF-1 (mecasermin), chiefly hypoglycemia. PEG-MGF is a pegylated copy of a muscle splice variant fragment whose pegylated form has no published pharmacology at all.", "verdict": { "winner": "a", "rationale": "This is a comparison of two unproven research chemicals with no lawful human use, so the verdict is about which is better documented, not which to use. Both are graded animal only. IGF-1 LR3 has in vivo rat data on potency and anabolic effect and a known class safety profile from the approved IGF-1 drug mecasermin, including hypoglycemia and a contraindication in cancer. PEG-MGF has only cell culture and mouse cardiac data on the unpegylated E domain peptide, and its 503A nomination was withdrawn. Neither can lawfully be compounded or sold for human use.", "source_ids": [ "tomas-1992", "francis-1992", "fda-increlex-label", "yang-2002", "carpenter-2013", "fda-503a-bulks" ] }, "dimensions": [ { "name": "What it is", "a": "Recombinant 83 amino acid IGF-1 analog with a 13 amino acid N-terminal extension and arginine at position 3, engineered in 1992 to escape IGF binding proteins.", "b": "Pegylated synthetic 24 amino acid peptide copying the E domain of mechano growth factor, a muscle splice variant of IGF-1 (IGF-1Ec).", "source_ids": [ "francis-1992", "yang-2002" ] }, { "name": "Mechanism", "a": "Activates the IGF-1 receptor (and binds the insulin receptor); binds IGF binding proteins poorly, so more stays free and active.", "b": "The E domain appears to activate muscle satellite cells and increase myoblast proliferation through a receptor other than the IGF-1 receptor.", "source_ids": [ "francis-1992", "yang-2002" ] }, { "name": "Animal evidence", "a": "In dexamethasone treated rats, about 2.5 fold more potent than IGF-1 on body weight and nitrogen retention, with less muscle protein breakdown and up to 45% more gut weight.", "b": "In myoblast culture the E domain increased proliferation and blocked differentiation; in mice a synthetic E domain peptide preserved heart function after infarction. The pegylated form has no published data.", "source_ids": [ "tomas-1992", "yang-2002", "carpenter-2013" ] }, { "name": "Human evidence", "a": "No human study of LR3. Class data come from mecasermin, approved native IGF-1 for severe primary IGF-1 deficiency in children.", "b": "No human study of any synthetic MGF peptide. Biopsies show natural MGF mRNA rises after resistance exercise in young but not older adults.", "source_ids": [ "fda-increlex-label", "hameed-2003" ] }, { "name": "Expected safety risks", "a": "Hypoglycemia (the most common mecasermin adverse effect, likely stronger with LR3), tonsillar hypertrophy, intracranial hypertension, and a cancer contraindication by class.", "b": "No human safety data of any kind; theoretical tumor growth concern shared with IGF-1 family peptides.", "source_ids": [ "fda-increlex-label", "goldspink-2005" ] }, { "name": "FDA and compounding status", "a": "Never nominated or reviewed. Not a component of an approved drug and not on the 503A bulks list, so it cannot lawfully be compounded.", "b": "Nominated and placed in 503A Category 2, then withdrawn; no longer in Category 2 but not on the bulks list, with no active nomination. Cannot lawfully be compounded.", "source_ids": [ "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Prohibited at all times under S2 (IGF-1 and its analogues).", "b": "Prohibited at all times under S2 (mechano growth factors are named).", "source_ids": [ "wada-list-s2-igf", "wada-list-s2-mgf" ] }, { "name": "Original intended use", "a": "Cell culture reagent designed to boost growth of cultured cells.", "b": "Research tool based on a hypothesized local muscle repair factor.", "source_ids": [ "francis-1992", "goldspink-2005" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Can I get IGF-1 LR3 or PEG-MGF from a doctor?", "a": "No lawful US channel exists for either. IGF-1 LR3 was never nominated for compounding, and the PEG-MGF nomination was withdrawn, so neither is on the 503A bulks list. 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 the same as the approved IGF-1 drug?", "a": "No. The approved drug, mecasermin, is native IGF-1 for children with severe primary IGF-1 deficiency. IGF-1 LR3 is a modified analog that escapes binding proteins and was about 2.5 fold more anabolic than IGF-1 in rats, which is also why its hypoglycemia risk is expected to be higher.", "source_ids": [ "fda-increlex-label", "tomas-1992" ] }, { "q": "Does PEG-MGF build muscle in humans?", "a": "There is no evidence it does. No human study has given PEG-MGF or any synthetic MGF peptide to people. The human data show only that the body's own MGF gene expression rises after heavy resistance exercise in young adults.", "source_ids": [ "hameed-2003", "goldspink-2005" ] }, { "q": "Are they banned in sport?", "a": "Yes. IGF-1 analogues and mechano growth factors are both prohibited at all times under S2 of the WADA Prohibited List.", "source_ids": [ "wada-list-s2-igf", "wada-list-s2-mgf" ] }, { "q": "What is the biggest known risk?", "a": "For IGF-1 LR3, hypoglycemia, the most common adverse effect of approved IGF-1, plus a class contraindication in active or suspected cancer. For PEG-MGF the risks are simply unknown because no human safety data exist.", "source_ids": [ "fda-increlex-label", "yang-2002" ] } ], "sources": [ { "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": "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": "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": "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": "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": "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": "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": "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": "wada-list-s2-igf", "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 }, { "id": "wada-list-s2-mgf", "type": "wada", "title": "WADA Prohibited List, section S2 (names mechano growth factors)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "ipamorelin-vs-ghrp-6", "a": "ipamorelin", "b": "ghrp-6", "title": "Ipamorelin vs GHRP-6", "summary": "Ipamorelin was designed as a cleaner GHRP-6: in the 1998 animal study that introduced it, it matched GHRP-6's growth hormone release in pigs without raising ACTH or cortisol. GHRP-6 has more human data, but only acute studies showing growth hormone, cortisol, and appetite increases; ipamorelin has one small IV pharmacology study showing growth hormone release in healthy men, and its only randomized trial, for postoperative ileus, was negative. Neither is approved, neither can be lawfully compounded in the US, and both are prohibited in sport.", "verdict": { "winner": "depends", "rationale": "GHRP-6 has the higher evidence grade (human_observational, from acute dosing studies), while ipamorelin is animal_only for growth hormone effects but showed better hormonal selectivity than GHRP-6 in the direct animal comparison. Regulatory status offers no tiebreak: GHRP-6 is in 503B Category 2, ipamorelin went through 503A Category 2 to a withdrawn nomination and ipamorelin acetate remains in 503B Category 2, and neither has a lawful compounding path. No human trial has compared them.", "source_ids": [ "raun-1998", "frieboes-1995", "beck-2014", "fda-category-2", "fda-503a-bulks", "gobburu-1999" ] }, "dimensions": [ { "name": "Structure", "a": "Pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), derived from the GHRP series.", "b": "Hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), the original GHRP described in 1984.", "source_ids": [ "raun-1998", "bowers-1984" ] }, { "name": "Direct animal comparison", "a": "In conscious pigs, GH release with potency and efficacy similar to GHRP-6 (ED50 about 2.3 nmol/kg), with no rise in ACTH or cortisol even at 200 times the GH ED50.", "b": "Similar GH release but also raised ACTH and cortisol in the same study.", "source_ids": [ "raun-1998" ] }, { "name": "Human evidence", "a": "One randomized trial (117 adults after bowel resection, intravenous): no significant effect on time to first tolerated meal (25.3 versus 32.6 hours, p = 0.15). No human GH data published.", "b": "Acute placebo controlled sleep study: four overnight 50 ug boluses raised GH, ACTH, cortisol, and stage 2 sleep. Oral dosing released GH in short children.", "source_ids": [ "beck-2014", "frieboes-1995", "bellone-1995" ] }, { "name": "Evidence grade", "a": "Animal only for GH related uses.", "b": "Human observational (acute pharmacology only, no chronic trial).", "source_ids": [ "raun-1998", "beck-2014", "frieboes-1995" ] }, { "name": "Appetite and metabolic effects", "a": "Increased appetite reported anecdotally; ghrelin receptor activity also speeds gut motility, the basis of the ileus program.", "b": "Marked increase in hunger is its most consistent effect; FDA cited reduced insulin sensitivity and higher blood glucose.", "source_ids": [ "venkova-2009", "camanni-1998", "fda-category-2" ] }, { "name": "Studied doses", "a": "Human trial: 0.03 mg/kg intravenously twice daily for up to 7 days. No subcutaneous dose established.", "b": "Acute studies: 1 ug/kg or 4 x 50 ug intravenously; 300 ug/kg orally in children. No chronic dose established.", "source_ids": [ "beck-2014", "frieboes-1995", "bellone-1995" ] }, { "name": "FDA compounding status", "a": "503A Category 2 in September 2023, nominations withdrawn in 2024 and listed as a withdrawn nomination in April 2026; ipamorelin acetate remains in 503B Category 2.", "b": "503B Category 2 since September 2023, still listed as of April 2026; no 503A nomination or listing.", "note": "Neither can be lawfully compounded; both are prohibited under WADA section S2.", "source_ids": [ "fda-503a-bulks", "fda-category-2", "wada-list" ] } ], "head_to_head_studies": [ { "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, with GHRP-6 as comparator", "population": "Rats and pigs (animal study)", "outcome": "Ipamorelin released GH with potency and efficacy comparable to GHRP-6 but, unlike GHRP-6, did not raise ACTH or cortisol", "grade": "animal_only", "url": "https://pubmed.ncbi.nlm.nih.gov/9849822/" } ], "faqs": [ { "q": "Is ipamorelin better than GHRP-6?", "a": "It may be more selective: in the animal study that introduced it, ipamorelin released as much GH as GHRP-6 without raising ACTH or cortisol. But GHRP-6 has more human data, and no human trial has compared them, so there is no evidence ipamorelin is better in people.", "source_ids": [ "raun-1998", "frieboes-1995" ] }, { "q": "Does GHRP-6 raise cortisol?", "a": "Yes. In a placebo controlled study in healthy men, overnight GHRP-6 boluses raised ACTH and cortisol along with GH. Reviews of the class also note prolactin increases.", "source_ids": [ "frieboes-1995", "camanni-1998" ] }, { "q": "Which one causes more hunger?", "a": "GHRP-6 is known for strong appetite stimulation. Ipamorelin also acts on the ghrelin receptor and increased appetite is reported anecdotally, but no human study has measured it.", "source_ids": [ "camanni-1998", "raun-1998" ] }, { "q": "Can I get either one from a licensed pharmacy?", "a": "No. GHRP-6 is in 503B Category 2 with no 503A pathway, and ipamorelin has only a withdrawn 503A nomination plus a 503B Category 2 listing for the acetate, so neither can be lawfully compounded.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Are they detectable in drug tests?", "a": "Yes. Both are prohibited under WADA section S2, and anti-doping methods detect urinary metabolites of GHRP-6 and ipamorelin after nasal dosing.", "source_ids": [ "wada-list", "semenistaya-2015" ] } ], "sources": [ { "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": "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": "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": "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" }, { "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" }, { "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" }, { "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "ipamorelin-vs-mk-677", "a": "ipamorelin", "b": "mk-677", "title": "Ipamorelin vs MK-677 (ibutamoren)", "summary": "Both activate the ghrelin receptor to release growth hormone, but MK-677 is an oral small molecule with years of randomized human data, while ipamorelin is an injectable peptide with one small IV pharmacology study showing growth hormone release in healthy men and otherwise animal evidence. MK-677's trials show what these drugs actually do in people: 25 mg daily for 2 years added about 1.1 kg of fat free mass without improving strength, raised fasting glucose, and a hip fracture trial was stopped for a heart failure signal. Neither is approved, neither can be lawfully compounded, and both are prohibited in sport.", "verdict": { "winner": "depends", "rationale": "On evidence, MK-677 is far better characterized (human_rct, including a 2 year trial in 65 older adults) than ipamorelin (animal_only for marketed uses). But that evidence shows modest lean mass gain with no functional benefit and real harms, and FDA keeps MK-677 in both 503A and 503B Category 2 over the heart failure signal, while ipamorelin's nomination was withdrawn after its own Category 2 listing. Neither has a lawful US access path, so there is no scenario where one is a recommended choice over the other.", "source_ids": [ "nass-2008", "adunsky-2011", "fda-category-2", "raun-1998", "beck-2014", "fda-503a-bulks", "gobburu-1999" ] }, "dimensions": [ { "name": "Molecule and route", "a": "Synthetic pentapeptide, given by injection (subcutaneous as sold; intravenous in the only human trial).", "b": "Non peptide small molecule taken orally once daily; its half life supports daily dosing.", "source_ids": [ "beck-2014", "chapman-1996" ] }, { "name": "Evidence grade", "a": "Animal only for GH related uses: selective GH release in rats and pigs, bone growth in rats.", "b": "Human RCT: several randomized placebo controlled trials from 4 weeks to 2 years in older adults, obese men, and people with Alzheimer disease.", "source_ids": [ "raun-1998", "johansen-1999", "nass-2008", "svensson-1998", "sevigny-2008" ] }, { "name": "Human body composition data", "a": "None published; the only human RCT measured recovery of bowel function after surgery and found no significant benefit.", "b": "Two years of 25 mg daily in 65 adults aged 60 to 81: fat free mass up about 1.1 kg versus placebo, no gain in strength or function. Eight weeks in 24 obese men: fat free mass up about 3 kg, no fat loss.", "source_ids": [ "beck-2014", "nass-2008", "svensson-1998" ] }, { "name": "Hormonal selectivity", "a": "In animals it did not raise ACTH, cortisol, or prolactin even at 200 times the GH ED50.", "b": "Transient rises in cortisol and prolactin reported; raises 24 hour GH and IGF-1 into the young adult range in older people.", "source_ids": [ "raun-1998", "chapman-1996" ] }, { "name": "Safety signals", "a": "No signal versus placebo over 7 days of intravenous dosing; long term effects untested. FDA cited immunogenicity from aggregation and impurities.", "b": "Increased appetite, edema, muscle pain, higher fasting glucose and reduced insulin sensitivity over 2 years; a hip fracture trial was terminated early for a possible congestive heart failure signal.", "source_ids": [ "beck-2014", "fda-503a-bulks", "nass-2008", "adunsky-2011" ] }, { "name": "Literature dosing", "a": "Not established for GH use; the human trial used 0.03 mg/kg intravenously twice daily for up to 7 days.", "b": "Trials used 25 mg orally once daily, with 2 mg and 50 mg arms in early studies. Research doses only.", "source_ids": [ "beck-2014", "chapman-1996", "nass-2008" ] }, { "name": "FDA compounding status", "a": "503A Category 2 in September 2023; nominations withdrawn in 2024, now listed as a withdrawn nomination. Ipamorelin acetate remains in 503B Category 2.", "b": "503B Category 2 since December 2022 and 503A Category 2 since September 2023, citing the heart failure risk; still in both as of April 2026. It also may not be sold as a dietary supplement.", "note": "Both are prohibited at all times under WADA section S2.", "source_ids": [ "fda-503a-bulks", "fda-category-2", "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Do ipamorelin and MK-677 work the same way?", "a": "Yes, both activate the ghrelin receptor (GHS-R1a) to release growth hormone. The difference is form: ipamorelin is an injected peptide, MK-677 is an oral small molecule taken once daily.", "source_ids": [ "raun-1998", "chapman-1996" ] }, { "q": "Which has better human evidence?", "a": "MK-677, by a wide margin. It has randomized trials up to 2 years long, including one where 25 mg daily raised fat free mass by about 1.1 kg versus placebo in older adults. Ipamorelin has no human trial measuring IGF-1 or body composition; its human growth hormone data are one small IV pharmacology study showing growth hormone release in healthy men.", "source_ids": [ "nass-2008", "beck-2014", "gobburu-1999" ] }, { "q": "Does MK-677 build muscle strength?", "a": "Not in the best trial. The 2 year study found a lean mass gain without any improvement in strength or physical function, along with higher fasting glucose and reduced insulin sensitivity.", "source_ids": [ "nass-2008" ] }, { "q": "Why does FDA consider MK-677 a safety risk?", "a": "A phase 2b trial in hip fracture patients was stopped early because of a possible congestive heart failure signal, and FDA cited that when it placed ibutamoren in both the 503A and 503B Category 2 lists.", "source_ids": [ "adunsky-2011", "fda-category-2" ] }, { "q": "Can I get either one legally?", "a": "No. Neither is FDA approved, MK-677 is in Category 2 for both pharmacy types, and ipamorelin has no active nomination or bulks list entry, so licensed pharmacies cannot compound either. Products sold as research chemicals or supplements are not lawful for human use.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] } ], "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": "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone secretagogues, including ipamorelin and ibutamoren)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "kisspeptin-10-vs-gonadorelin", "a": "kisspeptin-10", "b": "gonadorelin", "title": "Kisspeptin-10 vs gonadorelin", "summary": "Gonadorelin is the better supported and the only lawfully obtainable option of the two. It is native GnRH, was the active ingredient of two FDA approved products, and pulsatile pump delivery has decades of clinical data for ovulation and spermatogenesis induction. Kisspeptin-10 acts one step upstream, has only small physiology studies in healthy volunteers with no clinical endpoint, and sits on the FDA 503A Category 2 list, so it cannot be lawfully compounded. Both are prohibited by WADA.", "verdict": { "winner": "b", "rationale": "Gonadorelin wins on evidence and on regulatory status. Its human evidence includes a 2018 meta-analysis of 35 studies (1,002 women) for pulsatile GnRH in hypothalamic amenorrhea and a 42 patient series in hypogonadotropic men, and because it was a component of the discontinued FDA approved products Factrel and Lutrepulse a 503A pharmacy can compound it under a prescription. Kisspeptin-10 has physiology studies in groups of 4 to 15 healthy volunteers, no study of any clinical endpoint, and has been in FDA Category 2 since September 29, 2023, which leaves no lawful route to obtain it. The caveat is that the most common real world use of gonadorelin, intermittent injections 2 to 3 times a week alongside testosterone, has no published study either.", "source_ids": [ "tranoulis-2018", "buchter-1998", "jayasena-2011", "yeung-2026", "fda-cat2", "drugs-at-fda" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Human observational. Intravenous and subcutaneous physiology studies in healthy men and women (n = 4 to 5 per group in 2011) and a 2026 randomized, single-blind study in 15 healthy men that measured hormone levels, not a clinical outcome.", "b": "Human observational. A 2018 systematic review and meta-analysis of 35 studies (1,002 women) of pulsatile GnRH in hypothalamic amenorrhea, a 25 year single center cohort, and a 42 patient series in hypogonadotropic men.", "note": "Neither peptide has a randomized trial with a clinical endpoint such as pregnancy or testosterone normalization in a patient population.", "source_ids": [ "jayasena-2011", "yeung-2026", "tranoulis-2018", "quaas-2022", "buchter-1998" ] }, { "name": "Direct comparison", "a": "In a crossover physiology study in healthy men, intravenous kisspeptin-10 stimulated LH and FSH with a different time profile from GnRH.", "b": "In the same study, intravenous GnRH (gonadorelin) stimulated LH and FSH; all three peptides tested (kisspeptin-10, kisspeptin-54, GnRH) raised gonadotropins.", "note": "This is the only direct comparison and it measured hormone responses in healthy volunteers, not a treatment outcome.", "source_ids": [ "jayasena-2015" ] }, { "name": "Mechanism", "a": "Binds KISS1R on hypothalamic GnRH neurons and triggers endogenous pulsatile GnRH release, one step upstream of the pituitary. Circulating half-life of minutes; continuous exposure can desensitize the response.", "b": "Is GnRH itself. Binds GnRH receptors on pituitary gonadotrophs to release LH and FSH. Plasma half-life about 2 to 4 minutes; continuous or high dose exposure downregulates the receptor and suppresses gonadotropins.", "source_ids": [ "jayasena-2011", "dwyer-2024" ] }, { "name": "Clinical uses with evidence", "a": "None. No study has tested kisspeptin-10 for fertility, hypogonadism, or sexual function. The one randomized trial in a patient population (men with hypoactive sexual desire disorder) used kisspeptin-54, not kisspeptin-10.", "b": "Ovulation induction in hypothalamic amenorrhea and spermatogenesis induction in hypogonadotropic hypogonadism, both by pulsatile pump. Single dose diagnostic testing of pituitary LH response (former Factrel label).", "source_ids": [ "mills-2023", "tranoulis-2018", "buchter-1998", "drugs-at-fda" ] }, { "name": "Regulatory status", "a": "Not FDA approved. Placed on the FDA 503A Category 2 list on September 29, 2023, citing immunogenicity risk, peptide impurities, and limited safety information. Still in Category 2 as of the FDA page current to April 22, 2026, and not among the peptides reviewed by the advisory committee in July 2026.", "b": "Active ingredient of two FDA approved human products (Factrel and Lutrepulse), both discontinued for commercial rather than safety reasons. As a component of approved drugs it is eligible for 503A compounding and is not on the Category 2 list.", "source_ids": [ "fda-cat2", "drugs-at-fda", "fda-compounding-qa" ] }, { "name": "Lawful access in the United States", "a": "None outside a clinical trial. Products sold as research chemicals are not lawful for human use and are not verified for purity.", "b": "Prescription filled by a 503A compounding pharmacy, usually through testosterone telehealth clinics, or pump therapy through a reproductive endocrinology clinic.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "name": "Typical cost", "a": "Not available through licensed channels.", "b": "Compounded gonadorelin through telehealth testosterone clinics typically runs 50 to 150 USD per month.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "name": "Side effects", "a": "No adverse effects reported in short research protocols in healthy volunteers. Continuous exposure can suppress gonadotropins. No long term human safety data.", "b": "Injection or infusion site reactions, headache, nausea, flushing, rare hypersensitivity including anaphylaxis, antibody formation with prolonged use, ovarian hyperstimulation and multiple pregnancy in women, and paradoxical suppression of LH and FSH if given continuously.", "source_ids": [ "jayasena-2011", "yeung-2026", "tranoulis-2018", "drugs-at-fda" ] }, { "name": "WADA status", "a": "Prohibited (non-approved substance under S0 and a hormone modulator under S2).", "b": "Prohibited in male athletes under S2 (GnRH and its analogs).", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [ { "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 of intravenous kisspeptin-10, kisspeptin-54, and GnRH", "population": "Healthy men", "outcome": "All three peptides stimulated LH and FSH; the time profiles of the gonadotropin responses differed by peptide", "grade": "human_observational", "url": "https://pubmed.ncbi.nlm.nih.gov/26089302/" } ], "faqs": [ { "q": "Which one has better evidence, kisspeptin-10 or gonadorelin?", "a": "Gonadorelin. Pulsatile GnRH has a 2018 meta-analysis of 35 studies in 1,002 women with hypothalamic amenorrhea and a 42 patient series in hypogonadotropic men in which it induced sperm in 54 of 57 treatment courses. Kisspeptin-10 has physiology studies in healthy volunteers that measured LH, FSH, and testosterone and no study of a clinical endpoint.", "source_ids": [ "tranoulis-2018", "buchter-1998", "jayasena-2011", "yeung-2026" ] }, { "q": "Can I get kisspeptin-10 from a compounding pharmacy?", "a": "No. FDA placed kisspeptin-10 on the 503A Category 2 list in September 2023 and it remains there as of the page current to April 22, 2026, which means a 503A pharmacy may not compound it. Gonadorelin, by contrast, is a component of formerly approved FDA drugs and can be compounded under a prescription.", "source_ids": [ "fda-cat2", "fda-compounding-qa", "drugs-at-fda" ] }, { "q": "Is either one proven as an add-on to testosterone therapy?", "a": "No. There is no published study of intermittent subcutaneous gonadorelin injections 2 to 3 times per week as a testosterone therapy adjunct, and kisspeptin-10 has never been tested in that setting. Gonadorelin's evidence is for pulsatile pump delivery every 60 to 120 minutes.", "source_ids": [ "tranoulis-2018", "dwyer-2024", "yeung-2026" ] }, { "q": "How do they differ in mechanism?", "a": "Kisspeptin-10 acts on KISS1R on hypothalamic GnRH neurons and makes the body release its own GnRH in pulses. Gonadorelin is GnRH and acts directly on the pituitary. Both have half-lives of minutes and both lose effect with continuous exposure, which is why chronic protocols use pulses or intermittent infusions.", "source_ids": [ "jayasena-2011", "yeung-2026", "dwyer-2024" ] }, { "q": "Are they allowed in sport?", "a": "Neither is allowed. Gonadorelin is prohibited in male athletes under WADA section S2 as a GnRH analog, and kisspeptin-10 is prohibited as a non-approved substance under S0 and as a hormone modulator.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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", "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "kpv-vs-ll-37", "a": "kpv", "b": "ll-37", "title": "KPV vs LL-37", "summary": "LL-37 is the only one of the two with human trials, but those tested a topical gel on venous leg ulcers, and the larger phase IIb trial missed its primary endpoint. KPV has only mouse colitis data. Neither has any human data for injection, the form both are usually sold in, and their regulatory paths now differ: KPV was recommended for the 503A bulks list in July 2026, while LL-37 was not and is rarely compounded.", "verdict": { "winner": "depends", "rationale": "LL-37 has the higher evidence grade (human RCT) because a 34 patient phase I/II trial found faster venous ulcer healing with the two lower gel doses, but a larger phase IIb trial did not confirm it overall, and no data exist for injected LL-37. KPV is animal only; it was recommended for the 503A bulks list in July 2026 but awaits an FDA final rule, so neither has a lawful compounded path today. For a chronic wound, LL-37 gel is the one with human data; for gut inflammation or systemic use, neither has human evidence.", "source_ids": [ "gronberg-2014", "mahlapuu-2021", "dalmasso-2008", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic tripeptide (lysine-proline-valine), the C-terminal fragment of alpha-MSH.", "b": "Human cathelicidin antimicrobial peptide (37 amino acids) cleaved from the hCAP18 precursor.", "source_ids": [ "dalmasso-2008", "vandamme-2012" ] }, { "name": "Mechanism", "a": "Taken into gut and immune cells by PepT1, then inhibits NF-kB and MAP kinase inflammatory signaling.", "b": "Disrupts bacterial membranes, neutralizes lipopolysaccharide, recruits immune cells through FPR2, and stimulates keratinocyte migration and angiogenesis.", "source_ids": [ "dalmasso-2008", "vandamme-2012" ] }, { "name": "Direction of immune effect", "a": "Anti-inflammatory: dampens cytokine release.", "b": "Mixed: antimicrobial and pro healing at low concentrations, but pro inflammatory and cytotoxic at high concentrations and elevated in psoriasis and rosacea lesions.", "source_ids": [ "kannengiesser-2008", "vandamme-2012" ] }, { "name": "Human evidence", "a": "No indexed human trial for any indication.", "b": "Two randomized trials of topical gel in venous leg ulcers: faster healing at the two lower concentrations in 34 patients; the phase IIb trial missed its primary endpoint overall.", "source_ids": [ "dalmasso-2008", "gronberg-2014", "mahlapuu-2021" ] }, { "name": "Main animal evidence", "a": "Reduced DSS and TNBS colitis in mice, confirmed by a second lab in DSS and T cell transfer colitis.", "b": "Accelerated wound healing and protected against bacterial infection in rodent skin, lung, and sepsis models.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008", "vandamme-2012" ] }, { "name": "Theoretical safety concern", "a": "Immune dampening could impair response to infection (not shown).", "b": "May worsen psoriasis, rosacea, or lupus, where it is thought to drive inflammation; cytotoxic at high concentrations.", "source_ids": [ "dalmasso-2008", "vandamme-2012" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026 and recommended for the 503A bulks list by PCAC in July 2026; no final rule yet.", "b": "Withdrawn from 503A Category 2 after its nomination was withdrawn, and not among the peptides PCAC recommended in July 2026, so it sits in neither category and has no lawful compounded path.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Prohibited at all times under S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Typical cost and access", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "No lawful compounded price: off Category 2 but not on the 503A bulks list and not recommended by PCAC. Research chemical vials are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which has better evidence, KPV or LL-37?", "a": "LL-37, but only for a topical gel on venous leg ulcers: a 34 patient trial showed faster healing at the two lower doses, while a larger phase IIb trial missed its primary endpoint. KPV has only mouse data. Neither has human data for injection.", "source_ids": [ "gronberg-2014", "mahlapuu-2021", "dalmasso-2008" ] }, { "q": "Which is better for gut inflammation?", "a": "Neither has been tested in people with gut inflammation. KPV has two independent mouse colitis studies; LL-37 was studied for skin wounds and infection, not bowel disease.", "source_ids": [ "dalmasso-2008", "kannengiesser-2008", "vandamme-2012" ] }, { "q": "Can LL-37 make inflammatory skin disease worse?", "a": "Possibly. LL-37 is elevated in psoriasis and rosacea lesions, where it can complex with self DNA and RNA to activate immune cells, so it is thought to drive inflammation in those conditions. KPV works in the opposite direction by dampening inflammatory signaling.", "source_ids": [ "vandamme-2012", "dalmasso-2008" ] }, { "q": "Can a pharmacy compound KPV or LL-37?", "a": "Not from bulk today. KPV was removed from Category 2 and recommended for the 503A bulks list in July 2026, but the recommendation is advisory: until FDA publishes a final rule, a 503A pharmacy has no federal basis to compound it from bulk. LL-37 is off Category 2 but was not recommended, so it sits in neither category and has no lawful compounded path.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are KPV and LL-37 allowed in sport?", "a": "No. Both are prohibited at all times under S0 of the WADA Prohibited List as non-approved substances.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "KPV vs LL-37: evidence, immune effects, legal status", "description": "KPV vs LL-37: opposite immune effects, mouse colitis data vs topical leg ulcer trials, safety, WADA status, and why neither has a lawful compounded path." } }, { "slug": "leuprolide-vs-degarelix", "a": "leuprolide", "b": "degarelix", "title": "Leuprolide vs degarelix", "summary": "Both are FDA approved injections that lower testosterone to castrate levels for advanced prostate cancer, and in their direct 610 patient trial they were equally effective at 1 year (96.4% versus 97.2% to 98.3% castrate from day 28 to day 364). Degarelix works faster and avoids the testosterone flare: 96% of men were castrate by day 3 versus none on leuprolide. Leuprolide has longer dosing intervals (up to every 6 months), many more indications, and far fewer injection site reactions (under 1% versus about 40%).", "verdict": { "winner": "depends", "rationale": "Both carry human RCT evidence and FDA approval, and the head-to-head trial met noninferiority for degarelix on castration maintenance. Degarelix is preferable when an immediate, flare free drop in testosterone matters, such as spinal metastases or urinary obstruction where a leuprolide flare could cause harm. Leuprolide is preferable for convenience (3, 4, or 6 month depots versus monthly degarelix injections), tolerability at the injection site, and non-prostate indications such as endometriosis, fibroids, and central precocious puberty.", "source_ids": [ "klotz-2008", "fda-lupron-label", "fda-firmagon-label", "leuprolide-study-group-1984" ] }, "dimensions": [ { "name": "Mechanism", "a": "GnRH receptor agonist: first stimulates then downregulates pituitary receptors, causing a 1 to 2 week testosterone flare before suppression.", "b": "GnRH receptor antagonist: blocks the receptor immediately, with no initial surge and no microsurges on repeat dosing.", "source_ids": [ "fda-lupron-label", "fda-firmagon-label", "klotz-2008" ] }, { "name": "Speed of testosterone suppression", "a": "0% castrate by day 3; median testosterone rose about 65% in the first week before falling.", "b": "96% castrate by day 3, with a faster PSA decline.", "source_ids": [ "klotz-2008" ] }, { "name": "Castration maintenance at 1 year", "a": "96.4% with testosterone at or below 0.5 ng/mL from day 28 to day 364 (7.5 mg monthly).", "b": "97.2% (240/80 mg) and 98.3% (240/160 mg), meeting noninferiority.", "source_ids": [ "klotz-2008" ] }, { "name": "Dosing interval", "a": "Depots every 1, 3, 4, or 6 months (Lupron Depot 7.5, 22.5, 30, or 45 mg; Eligard, Camcevi).", "b": "240 mg loading dose as two injections, then 80 mg every 28 days.", "source_ids": [ "fda-lupron-label", "fda-firmagon-label" ] }, { "name": "Injection site reactions", "a": "Under 1% in the head-to-head trial; occasional sterile abscess with intramuscular depot.", "b": "About 40%, mostly pain, redness, swelling, or nodules after the loading dose.", "source_ids": [ "klotz-2008", "fda-lupron-label" ] }, { "name": "FDA indications", "a": "Advanced prostate cancer (since 1985), endometriosis, uterine fibroids, and central precocious puberty; generic available.", "b": "Advanced prostate cancer only (Firmagon, December 2008); no generic.", "source_ids": [ "fda-lupron-label", "fda-firmagon-label" ] }, { "name": "Survival evidence", "a": "Matched diethylstilbestrol for response and 1 year survival with fewer cardiovascular side effects; adding flutamide extended median survival from 28.3 to 35.6 months.", "b": "No survival trial; approval based on testosterone suppression versus leuprolide. A lower cardiovascular event rate in men with heart disease has been suggested in pooled analyses but not confirmed.", "source_ids": [ "leuprolide-study-group-1984", "crawford-1989", "klotz-2008" ] }, { "name": "WADA status", "a": "Prohibited in males under S2 as a GnRH analog.", "b": "Not prohibited.", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "Lupron Depot 7.5 mg roughly 2,000 to 2,500 USD per monthly injection at list; Eligard and generics lower.", "b": "Roughly 600 to 900 USD per monthly 80 mg injection at list; the loading dose costs about twice that.", "note": "Both are usually covered by Medicare Part B and commercial insurance for prostate cancer.", "source_ids": [ "fda-lupron-label", "fda-firmagon-label" ] } ], "head_to_head_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 prostate cancer of any stage requiring androgen deprivation therapy", "outcome": "Testosterone 0.5 ng/mL or below from day 28 to 364 in 97.2% (degarelix 240/80 mg) and 98.3% (240/160 mg) versus 96.4% with leuprolide 7.5 mg; 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/" } ], "faqs": [ { "q": "Is degarelix better than leuprolide for prostate cancer?", "a": "At 1 year they suppress testosterone equally well (97.2% to 98.3% versus 96.4% in the direct trial). Degarelix gets there much faster, castrate by day 3 in 96% of men versus none on leuprolide, and avoids the flare. Leuprolide needs fewer injections and causes far fewer injection site reactions.", "source_ids": [ "klotz-2008" ] }, { "q": "What is the testosterone flare and why does it matter?", "a": "Leuprolide initially stimulates the pituitary, so testosterone rises for 1 to 2 weeks before falling; in the head-to-head trial median testosterone rose about 65% in week 1. In men with spinal metastases or urinary obstruction, that surge can worsen bone pain or cause compression, which is why an antiandrogen is often added or an antagonist such as degarelix is used.", "source_ids": [ "klotz-2008", "fda-lupron-label" ] }, { "q": "How often are the injections?", "a": "Degarelix is given every 28 days after a two injection loading dose. Leuprolide depots can be given every 1, 3, 4, or 6 months depending on the product and dose.", "source_ids": [ "fda-firmagon-label", "fda-lupron-label" ] }, { "q": "Can either be used for conditions other than prostate cancer?", "a": "Leuprolide can: it is approved for endometriosis, uterine fibroids, and central precocious puberty as well. Degarelix is approved only for advanced prostate cancer and is not indicated for women.", "source_ids": [ "fda-lupron-label", "fda-firmagon-label" ] }, { "q": "Are they prohibited for athletes?", "a": "Leuprolide is prohibited in male athletes under WADA section S2 as a GnRH analog. Degarelix, an antagonist that lowers testosterone, is not on the list.", "source_ids": [ "wada-list" ] } ], "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": "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": "fda-lupron-label", "type": "fda", "title": "FDA prescribing information for Lupron Depot (leuprolide acetate) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=lupron+depot" }, { "id": "fda-firmagon-label", "type": "fda", "title": "FDA prescribing information for Firmagon (degarelix) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=firmagon" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "liraglutide-vs-cagrilintide", "a": "liraglutide", "b": "cagrilintide", "title": "Liraglutide vs cagrilintide", "summary": "In the phase 2 trial that included both, once weekly cagrilintide 4.5 mg produced 10.8% weight loss at 26 weeks versus 9.0% with once daily liraglutide 3.0 mg, a statistically significant 1.8 point difference. Liraglutide is FDA approved, available as a generic, and has a cardiovascular benefit in type 2 diabetes (LEADER); cagrilintide is investigational alone and is being developed mainly as a combination with semaglutide.", "verdict": { "winner": "depends", "rationale": "Cagrilintide beat liraglutide on weight in the direct comparison and needs one injection a week instead of seven, but the margin was small and the trial lasted only 26 weeks. Liraglutide can be prescribed today, is sold as a lower cost generic, and has LEADER cardiovascular outcomes data; cagrilintide cannot be lawfully obtained outside a trial.", "source_ids": [ "cagrilintide-phase2", "leader", "fda-first-generics", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Liraglutide 3.0 mg daily: 9.0% (9.6 kg) weight loss at 26 weeks.", "b": "Cagrilintide 4.5 mg weekly: 10.8% (11.5 kg) weight loss at 26 weeks; lower doses (0.3 to 2.4 mg) produced smaller losses, from 6.0%.", "note": "Phase 2 trial of 706 adults without diabetes; placebo produced 3.0%. The difference between cagrilintide 4.5 mg and liraglutide was 1.8 points (p = 0.03).", "source_ids": [ "cagrilintide-phase2" ] }, { "name": "Mechanism", "a": "GLP-1 receptor agonist.", "b": "Long acting amylin analog that increases satiety through the amylin pathway.", "source_ids": [ "fda-saxenda-label", "cagrilintide-phase2" ] }, { "name": "Longer term evidence", "a": "SCALE (3,731 adults, 56 weeks): 8.4 kg versus 2.8 kg on placebo. LEADER: major adverse cardiovascular events hazard ratio 0.87 in type 2 diabetes.", "b": "Mainly in combination with semaglutide: REDEFINE 1 (3,417 adults, 68 weeks) showed 20.4% weight loss versus 3.0% on placebo.", "source_ids": [ "scale-obesity", "leader", "redefine-1" ] }, { "name": "Side effects", "a": "Nausea, diarrhea, constipation, and vomiting, highest during weekly dose escalation; boxed warning for thyroid C-cell tumors.", "b": "Gastrointestinal adverse events in 41% to 63% versus 32% on placebo, mainly nausea (20% to 47% versus 18%); injection site reactions.", "source_ids": [ "fda-saxenda-label", "cagrilintide-phase2" ] }, { "name": "Regulatory status", "a": "FDA approved (Victoza 2010, Saxenda 2014); generic liraglutide approved from December 2024.", "b": "Not FDA approved alone. A new drug application for the fixed combination with semaglutide was submitted to FDA in December 2025. Not eligible for compounding.", "source_ids": [ "fda-saxenda-label", "fda-first-generics", "cagrisema-nda", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited under section S0 while not approved by any regulator.", "source_ids": [ "wada-list" ] }, { "name": "Dosing frequency", "a": "Once daily injection, 0.6 mg escalated weekly to 3.0 mg.", "b": "Once weekly injection in trials (up to 4.5 mg alone, 2.4 mg in the semaglutide combination).", "source_ids": [ "fda-saxenda-label", "cagrilintide-phase2", "redefine-1" ] } ], "head_to_head_studies": [ { "pmid": "34798060", "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial", "year": 2021, "design": "Randomized, double blind, placebo and active (liraglutide 3.0 mg) controlled phase 2 trial, 26 weeks", "n": 706, "population": "Adults without diabetes with BMI 30 or higher, or 27 with hypertension or dyslipidemia", "outcome": "Weight loss 10.8% with cagrilintide 4.5 mg versus 9.0% with liraglutide 3.0 mg (difference 1.8 points, p = 0.03) and 3.0% with placebo", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/" } ], "faqs": [ { "q": "Does cagrilintide work better than liraglutide?", "a": "Slightly, in one 26 week phase 2 trial: 10.8% weight loss with cagrilintide 4.5 mg weekly versus 9.0% with liraglutide 3.0 mg daily.", "source_ids": [ "cagrilintide-phase2" ] }, { "q": "Can I get cagrilintide?", "a": "Not lawfully outside a clinical trial. It is not FDA approved and is not eligible for compounding; a combination with semaglutide has been submitted to FDA but was not approved on the verification date.", "source_ids": [ "fda-503a-bulks", "cagrisema-nda" ] }, { "q": "Is generic liraglutide available?", "a": "Yes. FDA approved the first generic liraglutide in December 2024, which lowers its cost relative to branded GLP-1 drugs.", "source_ids": [ "fda-first-generics" ] }, { "q": "Do they work the same way?", "a": "No. Liraglutide activates the GLP-1 receptor; cagrilintide mimics amylin, a different satiety hormone, which is why it is being combined with the GLP-1 drug semaglutide.", "source_ids": [ "fda-saxenda-label", "cagrilintide-phase2", "redefine-1" ] } ], "sources": [ { "id": "cagrilintide-phase2", "type": "pubmed", "title": "Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a randomised, placebo and active-controlled, dose-finding phase 2 trial. Lancet 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/", "pmid": "34798060", "year": 2021 }, { "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": "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" }, { "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" }, { "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" }, { "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": "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": "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 for weight management (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": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "liraglutide-vs-dulaglutide", "a": "liraglutide", "b": "dulaglutide", "title": "Liraglutide vs dulaglutide", "summary": "For type 2 diabetes the two are close: in the AWARD-6 head-to-head trial, once weekly dulaglutide 1.5 mg lowered HbA1c by 1.42 points versus 1.36 for once daily liraglutide 1.8 mg, meeting noninferiority with similar nausea rates. Both reduced cardiovascular events in large outcomes trials (LEADER and REWIND). The practical split is that liraglutide is also approved for weight management and now comes as a cheaper generic, while dulaglutide needs one injection a week instead of seven.", "verdict": { "winner": "depends", "rationale": "Glucose lowering and cardiovascular protection are essentially equivalent on randomized evidence (AWARD-6 noninferiority; LEADER hazard ratio 0.87 and REWIND hazard ratio 0.88), and both are FDA approved with human_rct grades. Choose liraglutide when weight management is the goal (Saxenda 3.0 mg is approved for it) or when generic pricing matters; choose dulaglutide when once weekly dosing will improve adherence.", "source_ids": [ "award-6", "leader", "rewind", "fda-saxenda-label", "fda-trulicity-label", "fda-first-generics" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "AWARD-6 (599 adults on metformin, 26 weeks): liraglutide 1.8 mg daily lowered HbA1c by 1.36 points.", "b": "Dulaglutide 1.5 mg weekly lowered HbA1c by 1.42 points; treatment difference minus 0.06 (95% CI minus 0.19 to 0.07), noninferior.", "source_ids": [ "award-6" ] }, { "name": "Dosing frequency", "a": "Subcutaneous injection once daily (half life about 13 hours).", "b": "Subcutaneous injection once weekly from a single dose pen (half life about 5 days).", "source_ids": [ "fda-victoza-label", "fda-trulicity-label" ] }, { "name": "Cardiovascular outcomes", "a": "LEADER (9,340 adults with type 2 diabetes, median 3.8 years): hazard ratio 0.87 for major adverse cardiovascular events; cardiovascular death hazard ratio 0.78.", "b": "REWIND (9,901 adults aged 50 and older with type 2 diabetes and prior cardiovascular disease or risk factors, median 5.4 years): hazard ratio 0.88.", "source_ids": [ "leader", "rewind" ] }, { "name": "FDA labeled indications", "a": "Victoza for type 2 diabetes; Saxenda 3.0 mg for chronic weight management.", "b": "Trulicity for type 2 diabetes in adults and children 10 and older and cardiovascular risk reduction in type 2 diabetes. No weight management indication.", "source_ids": [ "fda-victoza-label", "fda-saxenda-label", "fda-trulicity-label" ] }, { "name": "Weight loss", "a": "SCALE Obesity and Prediabetes: 8.4 kg versus 2.8 kg on placebo at 56 weeks with 3.0 mg daily.", "b": "Modest weight loss in diabetes trials (about 3 to 5 kg), with further dose related loss at 3.0 and 4.5 mg in AWARD-11; no dedicated obesity trial.", "source_ids": [ "scale-obesity", "award-11" ] }, { "name": "Gastrointestinal side effects", "a": "AWARD-6: nausea 18%, diarrhea 12%, vomiting 8%, dyspepsia 6%.", "b": "AWARD-6: nausea 20%, diarrhea 12%, vomiting 7%, dyspepsia 8%; 6% stopped for adverse events in each arm.", "source_ids": [ "award-6" ] }, { "name": "Generic availability and cost", "a": "Generic liraglutide approved from December 2024; cash prices for the diabetes strength roughly 200 to 500 USD per month; Saxenda list about 1,349 USD.", "b": "No generic; Trulicity list 1,006.93 USD per month (from 389 USD self-pay through the manufacturer pharmacy), often 25 USD with commercial coverage.", "note": "Prices at the verification date change often; see the cost pages.", "source_ids": [ "fda-first-generics", "fda-trulicity-label", "lilly-pricing-trulicity", "lillydirect-trulicity" ] }, { "name": "Compounding status", "a": "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. Generics are also marketed. Ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "b": "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. No bulk substance is available, so it is not a compounded product.", "source_ids": [ "fda-glp1-compounding", "fda-trulicity-label", "fda-drug-shortages-liraglutide", "fda-glp1-shortage-updates", "fda-drug-shortages-dulaglutide", "fda-first-generics" ] } ], "head_to_head_studies": [ { "pmid": "25018121", "title": "Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial", "year": 2014, "design": "Randomized, open label, phase 3 noninferiority trial, 26 weeks", "n": 599, "population": "Adults with type 2 diabetes on metformin with HbA1c 7.0% or higher", "outcome": "HbA1c minus 1.42 with dulaglutide 1.5 mg versus minus 1.36 with liraglutide 1.8 mg (difference minus 0.06, noninferior); similar gastrointestinal event rates", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/25018121/" } ], "faqs": [ { "q": "Which lowers blood sugar more, liraglutide or dulaglutide?", "a": "They are about equal. In AWARD-6, dulaglutide 1.5 mg weekly lowered HbA1c by 1.42 points and liraglutide 1.8 mg daily by 1.36 points over 26 weeks, a difference that met the trial's noninferiority test.", "source_ids": [ "award-6" ] }, { "q": "Which is better for weight loss?", "a": "Liraglutide, because the 3.0 mg dose (Saxenda) is approved and tested for weight management: 8.4 kg versus 2.8 kg on placebo at 56 weeks in SCALE. Dulaglutide has no obesity indication.", "source_ids": [ "scale-obesity", "fda-saxenda-label", "fda-trulicity-label" ] }, { "q": "Do both protect the heart?", "a": "Yes. LEADER found a hazard ratio of 0.87 for major adverse cardiovascular events with liraglutide, and REWIND found 0.88 with dulaglutide over a median 5.4 years in adults with prior cardiovascular disease or cardiovascular risk factors.", "source_ids": [ "leader", "rewind" ] }, { "q": "Is there a generic?", "a": "Liraglutide yes: FDA approved the first generic in December 2024. Dulaglutide has no generic as of the verification date.", "source_ids": [ "fda-first-generics", "fda-trulicity-label" ] }, { "q": "Can I switch from daily liraglutide to weekly dulaglutide?", "a": "Switching is common in practice, but neither label provides a conversion schedule and AWARD-6 did not study switching. Dulaglutide is started at the label dose regardless of the prior GLP-1; discuss timing with the prescriber.", "source_ids": [ "fda-trulicity-label", "award-6" ] } ], "sources": [ { "id": "award-6", "type": "pubmed", "title": "Dungan KM et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6). Lancet 2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25018121/", "pmid": "25018121", "year": 2014 }, { "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": "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": "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": "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": "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" }, { "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" }, { "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" }, { "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" }, { "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" }, { "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-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 }, { "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "Victoza vs Trulicity (liraglutide vs dulaglutide)", "description": "Victoza vs Trulicity: daily liraglutide against weekly dulaglutide on blood sugar, weight, heart outcomes, generics, and switching, with sources.", "h1": "Victoza vs Trulicity (liraglutide vs dulaglutide)" } }, { "slug": "liraglutide-vs-exenatide", "a": "liraglutide", "b": "exenatide", "title": "Liraglutide vs exenatide", "summary": "Liraglutide beat exenatide in both head-to-head trials: it lowered HbA1c by 1.12 points versus 0.79 against twice daily exenatide in LEAD-6, and by 1.48 versus 1.28 against once weekly exenatide in DURATION-6, where exenatide failed noninferiority. Liraglutide also reduced cardiovascular events in LEADER, while exenatide's EXSCEL trial was neutral, and liraglutide has a weight management indication and generic versions. Exenatide's main advantage is a once weekly option versus liraglutide's daily injection.", "verdict": { "winner": "a", "rationale": "Liraglutide wins on direct randomized evidence (LEAD-6 and DURATION-6), on cardiovascular outcomes (LEADER hazard ratio 0.87 versus EXSCEL hazard ratio 0.91, not superior to placebo), on label breadth (Saxenda for weight management), and on price now that generics are marketed. Both are FDA approved with human_rct grades; weekly exenatide remains reasonable for someone who will not inject daily and has no access to a newer weekly agent.", "source_ids": [ "lead-6", "duration-6", "leader", "exscel", "fda-saxenda-label", "fda-first-generics" ] }, "dimensions": [ { "name": "Head-to-head versus twice daily exenatide", "a": "LEAD-6 (464 adults, 26 weeks): liraglutide 1.8 mg daily lowered HbA1c by 1.12 points and weight by 3.24 kg; 54% reached HbA1c below 7%.", "b": "Exenatide 10 ug twice daily lowered HbA1c by 0.79 points and weight by 2.87 kg; 43% reached HbA1c below 7%.", "note": "Nausea was less persistent and minor hypoglycemia less frequent with liraglutide.", "source_ids": [ "lead-6" ] }, { "name": "Head-to-head versus once weekly exenatide", "a": "DURATION-6 (912 adults, 26 weeks): liraglutide 1.8 mg daily lowered HbA1c by 1.48 points.", "b": "Exenatide 2 mg weekly lowered HbA1c by 1.28 points and did not meet noninferiority.", "source_ids": [ "duration-6" ] }, { "name": "Molecule and half life", "a": "Acylated human GLP-1 analog (97% homology), half life about 13 hours, dosed once daily.", "b": "Synthetic exendin-4 (about 53% identity to GLP-1), half life about 2.4 hours for the immediate release form; the weekly form uses microspheres.", "source_ids": [ "fda-victoza-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Cardiovascular outcomes", "a": "LEADER (9,340 adults, median 3.8 years): hazard ratio 0.87 for major adverse cardiovascular events; cardiovascular death hazard ratio 0.78.", "b": "EXSCEL (14,752 adults, median 3.2 years): hazard ratio 0.91 (95% CI 0.83 to 1.00); noninferior, not superior to placebo.", "source_ids": [ "leader", "exscel" ] }, { "name": "FDA labeled indications", "a": "Victoza for type 2 diabetes; Saxenda 3.0 mg for chronic weight management.", "b": "Byetta and Bydureon BCise for type 2 diabetes only (Bydureon BCise also in children 10 and older).", "source_ids": [ "fda-victoza-label", "fda-saxenda-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Dosing frequency", "a": "Once daily subcutaneous injection, escalated 0.6 mg per week.", "b": "Twice daily before meals (Byetta 5 then 10 ug) or once weekly (Bydureon BCise 2 mg).", "source_ids": [ "fda-victoza-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Side effects that differ", "a": "Nausea peaks during escalation; small heart rate increase of 2 to 3 beats per minute.", "b": "Injection site nodules with the weekly microsphere form; anti-exenatide antibodies in a substantial minority; not recommended in severe renal impairment.", "note": "Both labels (weekly exenatide and liraglutide) carry the thyroid C-cell tumor boxed warning.", "source_ids": [ "fda-saxenda-label", "fda-bydureon-label", "fda-byetta-label" ] }, { "name": "Generic availability and cost", "a": "Generic liraglutide marketed since December 2024; cash roughly 200 to 500 USD per month for the diabetes strength.", "b": "No generic; Byetta and Bydureon BCise list roughly 800 to 1,000 USD per month.", "note": "Prices at the verification date change often; see the cost pages.", "source_ids": [ "fda-first-generics", "fda-bydureon-label" ] } ], "head_to_head_studies": [ { "pmid": "19515413", "title": "Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)", "year": 2009, "design": "Randomized, open label, parallel group trial, 26 weeks", "n": 464, "population": "Adults with type 2 diabetes on metformin, sulfonylurea, or both", "outcome": "HbA1c minus 1.12 with liraglutide 1.8 mg daily versus minus 0.79 with exenatide 10 ug twice daily; weight minus 3.24 versus minus 2.87 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/19515413/" }, { "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 oral glucose lowering drugs", "outcome": "HbA1c minus 1.48 with liraglutide 1.8 mg versus minus 1.28 with exenatide 2 mg weekly; exenatide did not meet noninferiority", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/23141817/" } ], "faqs": [ { "q": "Is liraglutide more effective than exenatide?", "a": "Yes, in both direct trials. LEAD-6 found HbA1c reductions of 1.12 versus 0.79 points against twice daily exenatide, and DURATION-6 found 1.48 versus 1.28 points against weekly exenatide, which failed noninferiority.", "source_ids": [ "lead-6", "duration-6" ] }, { "q": "Which has better heart protection?", "a": "Liraglutide. LEADER showed a 13% relative reduction in major adverse cardiovascular events (hazard ratio 0.87) and fewer cardiovascular deaths. EXSCEL showed exenatide was safe but did not significantly reduce events (hazard ratio 0.91).", "source_ids": [ "leader", "exscel" ] }, { "q": "Do they cause similar weight loss?", "a": "In type 2 diabetes they are close: 3.24 kg versus 2.87 kg in LEAD-6. Only liraglutide has a weight management approval, as Saxenda 3.0 mg daily.", "source_ids": [ "lead-6", "fda-saxenda-label" ] }, { "q": "Which is easier to take?", "a": "Weekly exenatide (Bydureon BCise) requires one injection a week, versus one a day for liraglutide and two a day for Byetta. The weekly exenatide form causes more injection site nodules.", "source_ids": [ "fda-bydureon-label", "fda-byetta-label", "fda-victoza-label" ] }, { "q": "Is either available as a cheaper generic?", "a": "Liraglutide is: FDA approved the first generic in December 2024, bringing cash prices down. Exenatide has no generic as of the verification date.", "source_ids": [ "fda-first-generics", "fda-bydureon-label" ] } ], "sources": [ { "id": "lead-6", "type": "pubmed", "title": "Buse JB et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19515413/", "pmid": "19515413", "year": 2009 }, { "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": "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": "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-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" }, { "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" }, { "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" }, { "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" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "liraglutide-vs-setmelanotide", "a": "liraglutide", "b": "setmelanotide", "title": "Liraglutide vs setmelanotide", "summary": "These drugs treat different people. Liraglutide is a GLP-1 agonist approved for common obesity and type 2 diabetes, with 8.4 kg average weight loss at 56 weeks in SCALE. Setmelanotide is an MC4R agonist approved only for rare obesity caused by POMC, PCSK1, or LEPR deficiency, Bardet-Biedl syndrome, or acquired hypothalamic obesity, where it produced at least 10% weight loss in 80% of POMC deficient patients.", "verdict": { "winner": "depends", "rationale": "The choice follows the diagnosis. For common obesity, liraglutide is approved and setmelanotide is not indicated. For obesity caused by a confirmed defect in the leptin to melanocortin pathway, or by hypothalamic injury, setmelanotide is the drug approved for that cause and restores the missing satiety signal directly. They have never been compared.", "source_ids": [ "fda-saxenda-label", "fda-imcivree-label", "clement-2020", "setmelanotide-ho-approval" ] }, "dimensions": [ { "name": "Who it is for", "a": "Adults and adolescents 12 and older with obesity or overweight with a weight related condition (Saxenda); adults and children 10 and older with type 2 diabetes (Victoza).", "b": "Imcivree: chronic weight management in obesity due to POMC, PCSK1, or LEPR deficiency (2020) or Bardet-Biedl syndrome (2022), extended to age 2 and older in December 2024, and acquired hypothalamic obesity in patients 4 and older (March 2026). Not indicated for common obesity.", "source_ids": [ "fda-saxenda-label", "fda-victoza-label", "fda-imcivree-label", "setmelanotide-ho-approval" ] }, { "name": "Mechanism", "a": "GLP-1 receptor agonist: slows gastric emptying and reduces appetite through gut hormone signaling.", "b": "Melanocortin-4 receptor agonist: restores the hypothalamic satiety signal lost when the leptin to POMC to MC4R pathway is broken.", "source_ids": [ "fda-saxenda-label", "fda-imcivree-label" ] }, { "name": "Weight loss evidence", "a": "SCALE (3,731 adults, 56 weeks): 8.4 kg versus 2.8 kg on placebo; 63.2% lost at least 5%.", "b": "80% of POMC or PCSK1 deficient and 45% of LEPR deficient patients lost at least 10% at one year (single arm phase 3); acquired hypothalamic obesity: BMI 15.8% lower versus 2.6% higher on placebo at 52 weeks.", "source_ids": [ "scale-obesity", "clement-2020", "setmelanotide-ho-approval" ] }, { "name": "Side effects", "a": "Nausea, diarrhea, constipation, vomiting; gallbladder disease; heart rate up 2 to 3 beats per minute; thyroid C-cell boxed warning.", "b": "Injection site reactions, skin darkening and hyperpigmentation, nausea, spontaneous erections, and a label warning about depression and suicidal ideation.", "source_ids": [ "fda-saxenda-label", "fda-imcivree-label" ] }, { "name": "Dosing", "a": "Once daily injection, 0.6 mg escalated weekly to 3.0 mg.", "b": "Once daily injection; adults start at 2 mg and increase to 3 mg; weight based dosing in young children.", "source_ids": [ "fda-saxenda-label", "fda-imcivree-label" ] }, { "name": "Regulatory status", "a": "FDA approved (Victoza 2010, Saxenda 2014); generics approved from December 2024.", "b": "FDA approved (Imcivree 2020, with expansions in 2022, 2024, and March 2026). Prescription only for the labeled conditions.", "source_ids": [ "fda-saxenda-label", "fda-first-generics", "fda-imcivree-label", "setmelanotide-ho-approval" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not on the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Can setmelanotide be used for ordinary weight loss?", "a": "No. It is approved only for obesity due to POMC, PCSK1, or LEPR deficiency, Bardet-Biedl syndrome, or acquired hypothalamic obesity, and the label excludes common obesity.", "source_ids": [ "fda-imcivree-label", "setmelanotide-ho-approval" ] }, { "q": "Which is better for hypothalamic obesity?", "a": "Setmelanotide is the approved option: in March 2026 FDA approved it for acquired hypothalamic obesity in patients 4 and older after a phase 3 trial showed an 18.4% greater BMI reduction than placebo at 52 weeks. Liraglutide is not labeled for this condition.", "source_ids": [ "setmelanotide-ho-approval", "fda-saxenda-label" ] }, { "q": "Are both daily injections?", "a": "Yes. Both liraglutide and setmelanotide are injected under the skin once a day.", "source_ids": [ "fda-saxenda-label", "fda-imcivree-label" ] }, { "q": "What side effects are unique to setmelanotide?", "a": "Skin and mole darkening, spontaneous erections, and a warning to monitor for depression and suicidal thoughts, none of which are typical of liraglutide.", "source_ids": [ "fda-imcivree-label", "fda-saxenda-label" ] } ], "sources": [ { "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" }, { "id": "fda-imcivree-label", "type": "fda", "title": "FDA prescribing information for Imcivree (setmelanotide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=imcivree" }, { "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: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33137293/", "pmid": "33137293", "year": 2020 }, { "id": "setmelanotide-ho-approval", "type": "other", "title": "Trade press report: FDA approves setmelanotide for acquired hypothalamic obesity in patients 4 and older (March 19, 2026), accessed 2026-09-22", "url": "https://www.docwirenews.com/post/fda-approves-expanded-indication-for-setmelanotide-as-first-and-only-approved-therapy-for-acquired-hypothalamic-obesity", "year": 2026 }, { "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" }, { "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": "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "melanotan-i-vs-melanotan-ii", "a": "melanotan-i", "b": "melanotan-ii", "title": "Melanotan I (afamelanotide) vs Melanotan II", "summary": "Melanotan I is the regulated one: as afamelanotide (Scenesse) it is an FDA approved implant for adults with erythropoietic protoporphyria, backed by two randomized phase 3 trials. Melanotan II has never been approved anywhere, has only two tiny erectile dysfunction trials, and carries case reports of serious harm. Neither is approved for cosmetic tanning, and injectable vials of either sold online are not lawful for human use.", "verdict": { "winner": "a", "rationale": "Afamelanotide is FDA approved and graded human RCT from two multicenter phase 3 trials in 168 patients with erythropoietic protoporphyria (for example, 6.0 versus 0.8 hours of pain-free sunlight exposure in the EU trial). It is selective for MC1R, so it lacks the sexual, appetite, and nausea effects of Melanotan II. Melanotan II is nonselective, has only two 10 man trials, has no lawful compounding basis, and has case reports of priapism, eruptive moles, renal infarction, and FDA cited melanoma reports. The win applies to the approved implant for its approved use, not to tanning.", "source_ids": [ "langendonk-2015", "scenesse-label", "wessells-1998", "wessells-2000", "fda-cat2" ] }, "dimensions": [ { "name": "What it is", "a": "Linear 13 amino acid alpha-MSH analog, selective MC1R agonist, delivered as a 16 mg controlled release implant.", "b": "Cyclic 7 amino acid alpha-MSH analog, nonselective agonist at MC1R, MC3R, MC4R, and MC5R.", "source_ids": [ "scenesse-label", "wessells-1998" ] }, { "name": "Effects beyond pigmentation", "a": "Little MC3R or MC4R activity, so no meaningful effect on sexual function or appetite.", "b": "Erections, increased sexual desire, reduced appetite, stretching and yawning, and nausea from MC3R and MC4R activation.", "source_ids": [ "wu-2021", "wessells-1998", "wessells-2000" ] }, { "name": "Human evidence", "a": "Two randomized, double-blind phase 3 trials in erythropoietic protoporphyria (94 and 74 patients): more pain-free sun exposure and fewer phototoxic reactions.", "b": "Two double-blind crossover trials of 10 men each with erectile dysfunction; no trial for tanning.", "source_ids": [ "langendonk-2015", "wessells-1998", "wessells-2000" ] }, { "name": "FDA status", "a": "FDA approved as Scenesse (October 2019) for adults with phototoxicity from erythropoietic protoporphyria; approved in the EU in 2014.", "b": "Not approved in any country; its Category 2 nomination was withdrawn but it is not on the bulks list or an approved drug component, so it cannot be compounded.", "source_ids": [ "scenesse-label", "fda-cat2" ] }, { "name": "Safety profile", "a": "Implant site reactions, nausea, headache, darkening of moles and new freckles; the label requires full body skin exams twice yearly.", "b": "Severe nausea in trials; case reports of eruptive moles within 24 hours, priapism, and renal infarction; FDA cites reports of melanoma and encephalopathy.", "source_ids": [ "scenesse-label", "wessells-2000", "schulze-2014", "dreyer-2019", "peters-2020", "fda-cat2" ] }, { "name": "Route and dosing", "a": "One 16 mg implant inserted under the skin every 2 months by a trained provider at a certified center.", "b": "Single 0.025 mg/kg subcutaneous injections in trials; tanning schedules sold online have no literature basis.", "source_ids": [ "scenesse-label", "wessells-1998" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited at all times under S0 (non-approved substances).", "source_ids": [ "wada-list", "wada-list-s0" ] }, { "name": "Cost and access", "a": "Specialty orphan drug priced in the tens of thousands of USD per implant before insurance, dispensed only through certified centers for the approved indication.", "b": "No lawful channel; gray market vials have been found unsterile or mislabeled.", "source_ids": [ "scenesse-label", "fda-compounding-qa" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Can I use Melanotan I for tanning?", "a": "Not lawfully. The approved product, Scenesse, is an implant for adults with erythropoietic protoporphyria dispensed through certified centers, and it is not approved for cosmetic tanning. Injectable Melanotan I sold online is not a compounded prescription product and is marketed unlawfully.", "source_ids": [ "scenesse-label", "fda-compounding-qa" ] }, { "q": "Why is Melanotan II riskier than Melanotan I?", "a": "Melanotan II activates several melanocortin receptors, which causes nausea, spontaneous erections, and appetite changes, and it has case reports of priapism, eruptive moles, and renal infarction. It was never taken through safety trials. Afamelanotide is MC1R selective and has phase 3 safety data under a label that requires skin surveillance.", "source_ids": [ "wessells-2000", "dreyer-2019", "peters-2020", "schulze-2014", "langendonk-2015" ] }, { "q": "Do either cause skin cancer?", "a": "Causation has not been shown for either, but both darken existing moles and can cause new ones. The Scenesse label requires full body skin exams twice yearly, and FDA has cited published case reports of melanoma associated with Melanotan II.", "source_ids": [ "scenesse-label", "fda-cat2", "schulze-2014" ] }, { "q": "Are they allowed in sport?", "a": "Afamelanotide is not on the WADA Prohibited List. Melanotan II is prohibited at all times under S0 as a non-approved substance.", "source_ids": [ "wada-list", "wada-list-s0" ] } ], "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": "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 }, { "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": "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": "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-list-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 2, "seo": { "title": "MT1 vs MT2: Melanotan I vs Melanotan II compared" } }, { "slug": "mots-c-vs-humanin", "a": "mots-c", "b": "humanin", "title": "MOTS-c vs humanin", "summary": "MOTS-c and humanin are both mitochondrial derived peptides with animal only evidence, so neither has a proven human benefit; the practical difference is regulatory. MOTS-c came off the FDA Category 2 list in April 2026 and received a favorable Pharmacy Compounding Advisory Committee vote in July 2026, while humanin has never been nominated for the 503A bulks list and has no lawful US route. Scientifically, MOTS-c is studied mainly for muscle metabolism and exercise capacity, humanin mainly for neuroprotection and cell survival.", "verdict": { "winner": "depends", "rationale": "Neither has evidence to support clinical use and neither can currently be lawfully compounded; MOTS-c has a pending PCAC recommendation, which is advisory. Both sit at the animal only evidence grade, and the human data for each are association studies of natural blood levels or genetics rather than treatment trials. Humanin also carries a theoretical tumor survival concern from its anti-apoptotic action that has not been studied in people.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "lee-2015", "reynolds-2021", "yen-2020", "hashimoto-2001" ] }, "dimensions": [ { "name": "Origin", "a": "16 amino acids, encoded in the mitochondrial 12S rRNA gene.", "b": "24 amino acids, encoded in the mitochondrial 16S rRNA gene (MT-RNR2).", "source_ids": [ "lee-2015", "hashimoto-2001" ] }, { "name": "Mechanism", "a": "Inhibits the folate cycle and purine synthesis, raising AICAR and activating AMPK, which increases muscle glucose uptake and fat oxidation; moves to the nucleus under metabolic stress.", "b": "Binds Bax and IGFBP-3 inside cells to block apoptosis and signals through a CNTFR, WSX-1, and gp130 receptor complex that activates STAT3.", "source_ids": [ "lee-2015", "hashimoto-2001", "muzumdar-2009" ] }, { "name": "Strongest animal findings", "a": "Prevented diet induced obesity and insulin resistance in mice (0.5 mg/kg daily) and improved running capacity in young and old mice (15 mg/kg).", "b": "Rescued neurons from Alzheimer's related death in culture, improved hepatic insulin sensitivity in rats, and the analog HNG improved metabolic healthspan and memory in middle aged mice without extending mean life span.", "source_ids": [ "lee-2015", "reynolds-2021", "hashimoto-2001", "muzumdar-2009", "yen-2020" ] }, { "name": "Human data", "a": "Blood and muscle levels rise acutely with exercise in 10 young men; a MOTS-c sequence variant is associated with type 2 diabetes in Japanese men. No treatment trial.", "b": "Higher plasma levels associated with preserved coronary endothelial function in 40 patients; levels decline with age and are higher in centenarian offspring. No treatment trial.", "source_ids": [ "reynolds-2021", "zempo-2021", "widmer-2013", "yen-2020" ] }, { "name": "Theoretical safety concerns", "a": "Possible added glucose lowering with diabetes drugs, extrapolated from mouse AMPK data.", "b": "Possible support of tumor cell survival from its anti-apoptotic, STAT3 activating action; possible added glucose lowering.", "note": "Neither concern has been tested in people because no human safety data exist for either peptide.", "source_ids": [ "lee-2015", "hashimoto-2001", "muzumdar-2009" ] }, { "name": "FDA and compounding status", "a": "Removed from the 503A Category 2 list on April 15, 2026; PCAC recommended adding it to the 503A bulks list on July 23 to 24, 2026; no final FDA rule at verification.", "b": "Not identified on any 503A nomination list or PCAC agenda, so a 503A pharmacy cannot lawfully compound it as a bulk substance.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Access and cost", "a": "No lawful compounded channel today: PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory and FDA has not published a final rule.", "b": "No lawful channel. Only research chemical listings, which are not lawful for human use or verified for purity.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Animal study dose ranges", "a": "0.5 mg/kg per day intraperitoneally (metabolic) up to 15 mg/kg (exercise) in mice.", "b": "0.1 to 4 mg/kg intraperitoneally in rodents; 2 to 4 mg/kg HNG twice weekly in the mouse healthspan study.", "note": "No human dose has been established for either peptide.", "source_ids": [ "lee-2015", "reynolds-2021", "muzumdar-2009", "yen-2020" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for longevity, MOTS-c or humanin?", "a": "Neither has been shown to extend life or healthspan in people. In mice, MOTS-c improved physical capacity in old animals and the humanin analog HNG improved metabolic healthspan and memory without extending mean life span. Human data for both are limited to blood level associations.", "source_ids": [ "reynolds-2021", "yen-2020" ] }, { "q": "Are MOTS-c and humanin the same kind of peptide?", "a": "Yes, both are mitochondrial derived peptides translated from short reading frames inside mitochondrial ribosomal RNA genes, but from different genes (12S for MOTS-c, 16S for humanin) and with different mechanisms: MOTS-c works through AMPK and metabolism, humanin through anti-apoptotic and STAT3 signaling.", "source_ids": [ "lee-2015", "hashimoto-2001", "muzumdar-2009" ] }, { "q": "Can I get a prescription for either one?", "a": "Not today. FDA removed MOTS-c from Category 2 and PCAC recommended it for the 503A bulks list in 2026, but the recommendation is advisory and FDA had not issued a final rule at verification, so a 503A pharmacy has no federal basis to compound it from bulk. Humanin has never been nominated and has no lawful US route.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are prohibited at all times: MOTS-c is named under WADA section S4.4 as a metabolic modulator, and humanin falls under section S0 as a non-approved substance.", "source_ids": [ "wada-list" ] }, { "q": "Does humanin protect against Alzheimer's disease?", "a": "Humanin was discovered because it protected cultured neurons from damage caused by Alzheimer's related genes and amyloid beta, but that work was in cells. No human trial has tested humanin or an analog for Alzheimer's disease or cognition.", "source_ids": [ "hashimoto-2001", "yen-2020" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 non-approved substances and section S4.4 metabolic modulators)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "mots-c-vs-ss-31", "a": "mots-c", "b": "ss-31", "title": "MOTS-c vs SS-31 (elamipretide)", "summary": "SS-31 (elamipretide) has the stronger evidence and regulatory standing: it has been tested in randomized human trials and received FDA accelerated approval as Forzinity for Barth syndrome in September 2025. MOTS-c has only mouse treatment data and human blood level associations. The caveat is that SS-31's trials were mixed, including a 218 patient mitochondrial myopathy trial that missed its primary endpoint, so neither peptide is proven for general mitochondrial health, energy, or aging.", "verdict": { "winner": "b", "rationale": "SS-31 wins on evidence grade (human RCT versus animal only) and regulatory status (an FDA approved drug versus a substance still awaiting a final FDA decision on the 503A bulks list). Its approval is narrow, limited to Barth syndrome and based on a small crossover trial that missed its primary endpoints plus a 168 week open label extension, and MMPOWER-3 found no benefit over placebo in primary mitochondrial myopathy. MOTS-c has no human treatment trial at all.", "source_ids": [ "reid-thompson-2021", "thompson-2024", "karaa-2023", "dailymed-forzinity", "lee-2015", "fda-pcac-2026" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Animal only. Mouse metabolic and exercise studies; human data are exercise induced blood levels and a genetic association with type 2 diabetes.", "b": "Human RCT. TAZPOWER (12 patients with Barth syndrome) and MMPOWER-3 (218 adults with primary mitochondrial myopathy), plus earlier phase 2 trials.", "source_ids": [ "lee-2015", "reynolds-2021", "zempo-2021", "reid-thompson-2021", "karaa-2023" ] }, { "name": "Mechanism", "a": "A 16 amino acid peptide encoded by mitochondrial DNA that signals outward: it activates AMPK via the folate cycle and AICAR, raising muscle glucose uptake and fat oxidation.", "b": "A synthetic tetrapeptide that works inside mitochondria: it binds cardiolipin on the inner membrane, stabilizing cristae and respiratory chain supercomplexes and improving ATP production.", "source_ids": [ "lee-2015", "birk-2013" ] }, { "name": "Key trial results", "a": "No human treatment trial. In mice, prevented diet induced obesity and insulin resistance and improved running capacity at all ages.", "b": "TAZPOWER missed its 12 week crossover endpoints but the open label extension showed sustained gains in 6 minute walk distance and strength at 168 weeks; MMPOWER-3 showed no significant difference from placebo at 24 weeks.", "source_ids": [ "lee-2015", "reynolds-2021", "reid-thompson-2021", "thompson-2024", "karaa-2023" ] }, { "name": "Human safety data", "a": "None published. Theoretical added glucose lowering with diabetes drugs based on mouse data.", "b": "Generally well tolerated in trials; injection site reactions were the most common adverse event, with headache, dizziness, and eosinophilia in some participants.", "source_ids": [ "lee-2015", "karaa-2023", "thompson-2024" ] }, { "name": "FDA and compounding status", "a": "Not FDA approved. Removed from the 503A Category 2 list on April 15, 2026; PCAC recommended it for the 503A bulks list in July 2026; no final rule at verification.", "b": "FDA approved (accelerated approval, Forzinity, September 2025) for Barth syndrome. Because an approved product exists, it is not eligible for routine 503A compounding.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "dailymed-forzinity" ] }, { "name": "WADA status", "a": "Prohibited at all times under S4.4 (metabolic modulators), where it is named as an activator of AMP-activated protein kinase.", "b": "Not prohibited.", "note": "Because elamipretide is now an approved drug, it no longer falls under S0.", "source_ids": [ "wada-list" ] }, { "name": "Human dosing reference", "a": "Not established. Mice received 0.5 mg/kg daily (metabolic studies) up to 15 mg/kg (exercise studies).", "b": "Trials used 40 mg subcutaneously once daily; the Forzinity label gives weight based dosing for Barth syndrome.", "source_ids": [ "lee-2015", "reynolds-2021", "karaa-2023", "dailymed-forzinity" ] }, { "name": "Access path", "a": "No lawful compounded channel today: PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory and FDA has not published a final rule.", "b": "Specialist prescription for Barth syndrome through specialty pharmacy; other uses only in clinical trials. Research listings labeled SS-31 are not the approved drug.", "source_ids": [ "fda-pcac-2026", "dailymed-forzinity" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for mitochondrial health or energy?", "a": "Neither has been shown to improve energy or mitochondrial health in healthy people. SS-31 is approved only for Barth syndrome and did not beat placebo in adults with primary mitochondrial myopathy in MMPOWER-3. MOTS-c has only mouse data.", "source_ids": [ "karaa-2023", "dailymed-forzinity", "reynolds-2021" ] }, { "q": "Is SS-31 FDA approved?", "a": "Yes. Elamipretide received accelerated approval as Forzinity in September 2025 for Barth syndrome, supported by the TAZPOWER trial and its 168 week open label extension. Products sold online as SS-31 for research are not the approved drug and are not lawful for human use.", "source_ids": [ "dailymed-forzinity", "reid-thompson-2021", "thompson-2024" ] }, { "q": "Can I get MOTS-c from a compounding pharmacy?", "a": "Not from bulk today. FDA removed MOTS-c from the Category 2 list in April 2026 and PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory: until FDA publishes a final rule it is not on the 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.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Do they work the same way?", "a": "No. SS-31 acts inside the mitochondrion by binding cardiolipin and stabilizing the respiratory chain. MOTS-c is a signaling peptide made from mitochondrial DNA that acts on the cell's metabolism through AMPK.", "source_ids": [ "birk-2013", "lee-2015" ] }, { "q": "Are they allowed for tested athletes?", "a": "MOTS-c is prohibited at all times under WADA section S4.4 (metabolic modulators). SS-31 is not prohibited now that it is an approved drug, though athletes should confirm against the current list.", "source_ids": [ "wada-list" ] } ], "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": "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/search.cfm?labeltype=all&query=forzinity" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "nad-plus-vs-mots-c", "a": "nad-plus", "b": "mots-c", "title": "NAD+ vs MOTS-c", "summary": "NAD+ has the stronger human evidence, but mostly for oral precursors: randomized trials show nicotinamide riboside raises blood NAD+ and nicotinamide mononucleotide improved muscle insulin sensitivity in prediabetic women, while MOTS-c has no human treatment trial at all. The caveat is that injectable and intravenous NAD+, the form clinics sell, has only an 11 person pharmacokinetic pilot. NAD+ is also not prohibited in sport, while MOTS-c is banned at all times.", "verdict": { "winner": "a", "rationale": "NAD+ wins on evidence grade (human RCT for precursors versus animal only), on WADA status, and on access, since oral precursors are lawful supplements that need no prescription. Both injectable forms are in regulatory limbo: NAD+ is a nominated 503A bulk substance compounded under FDA's interim policy, and MOTS-c is awaiting a final FDA rule after a favorable July 2026 PCAC vote. Anyone choosing NAD+ should know the trial evidence supports oral NR and NMN, not infusions, and that a 2025 meta-analysis found no effect on muscle mass or function.", "source_ids": [ "martens-2018", "yoshino-2021", "grant-2019", "prokopidis-2025", "lee-2015", "fda-503a-bulks", "fda-pcac-2026", "wada-list" ] }, "dimensions": [ { "name": "Evidence grade", "a": "Human RCT, for oral precursors: NR 1,000 mg per day raised blood NAD+ about 60% in 24 older adults; NMN 250 mg per day improved muscle insulin sensitivity about 25% in 25 prediabetic women.", "b": "Animal only. Mouse studies of obesity, insulin resistance, and running capacity; human data are exercise induced blood levels and a genetic association.", "source_ids": [ "martens-2018", "yoshino-2021", "lee-2015", "reynolds-2021", "zempo-2021" ] }, { "name": "What it is", "a": "A coenzyme (a dinucleotide, not a peptide) used in energy metabolism and consumed by sirtuins, PARP, and CD38.", "b": "A 16 amino acid peptide encoded in the mitochondrial 12S rRNA gene.", "source_ids": [ "rajman-2018", "lee-2015" ] }, { "name": "Mechanism", "a": "Restores cellular NAD+ that falls with age; precursors enter the salvage pathway. Intravenous NAD+ is largely broken down in blood before reaching cells.", "b": "Activates AMPK via folate cycle inhibition and AICAR accumulation, raising muscle glucose uptake and fat oxidation in mice.", "source_ids": [ "rajman-2018", "grant-2019", "lee-2015" ] }, { "name": "Injectable form evidence", "a": "One open label pilot: a 6 hour infusion in 11 healthy men, plasma NAD+ did not rise until the second hour and no clinical endpoints were measured.", "b": "No human study of injected MOTS-c; mice received 0.5 to 15 mg/kg.", "source_ids": [ "grant-2019", "lee-2015", "reynolds-2021" ] }, { "name": "Side effects", "a": "Oral precursors well tolerated in trials; IV NAD+ commonly causes chest pressure, nausea, cramping, and flushing when infused quickly.", "b": "No human safety data; theoretical added glucose lowering with diabetes drugs.", "source_ids": [ "martens-2018", "yoshino-2021", "lee-2015" ] }, { "name": "FDA and compounding status", "a": "Not FDA approved. Nominated for the 503A bulks list and compounded under FDA's interim enforcement policy where states permit; oral NR and NMN are sold as supplements.", "b": "Not FDA approved. Removed from Category 2 on April 15, 2026; PCAC recommended it for the 503A bulks list on July 23 to 24, 2026; no final rule at verification.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Not prohibited as a substance.", "b": "Prohibited at all times under S4.4 (metabolic modulators), where it is named as an activator of AMP-activated protein kinase.", "note": "Under WADA method M2, intravenous infusions or injections above 100 mL per 12 hour period are prohibited for athletes outside legitimate hospital care, which can apply to NAD+ drips.", "source_ids": [ "wada-list" ] }, { "name": "Cost and access", "a": "Oral NR or NMN roughly 30 to 100 USD per month over the counter; IV sessions 300 to 1,000 USD; compounded injections roughly 150 to 400 USD per month.", "b": "No lawful compounded channel today: PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory and FDA has not published a final rule.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is NAD+ or MOTS-c better for energy and aging?", "a": "Neither has shown an effect on energy, aging, or longevity in human trials. NAD+ precursors raise blood NAD+ and NMN improved muscle insulin sensitivity in one trial, but a 2025 meta-analysis found no effect on muscle mass or function. MOTS-c evidence is limited to mice.", "source_ids": [ "martens-2018", "yoshino-2021", "prokopidis-2025", "reynolds-2021" ] }, { "q": "Does IV NAD+ work better than oral precursors?", "a": "There is no evidence that it does. The only published infusion study was an 11 person pharmacokinetic pilot with no clinical endpoints, and it found that much of the infused NAD+ is broken down and excreted. The randomized trial evidence is for oral nicotinamide riboside and nicotinamide mononucleotide.", "source_ids": [ "grant-2019", "martens-2018", "yoshino-2021" ] }, { "q": "Can athletes use either one?", "a": "MOTS-c is prohibited at all times under WADA section S4.4 (metabolic modulators). NAD+ itself is not a prohibited substance, but IV drips above 100 mL per 12 hours fall under the prohibited method M2 outside legitimate hospital care.", "source_ids": [ "wada-list" ] }, { "q": "Do I need a prescription?", "a": "Not for oral NAD+ precursors, which are dietary supplements. Injectable NAD+ requires a prescription filled by a 503A compounding pharmacy. MOTS-c is not on the 503A bulks list, so a 503A pharmacy has no federal basis to compound it from bulk. Neither is an FDA approved drug.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Can they be combined?", "a": "No study has tested NAD+ and MOTS-c together, so there is no evidence on the combination's benefit or safety. Both are proposed to affect glucose metabolism, so people on diabetes medications should involve their prescriber.", "source_ids": [ "yoshino-2021", "lee-2015" ] } ], "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S4.4 metabolic modulators and method M2 on intravenous infusions)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "octreotide-vs-lanreotide", "a": "octreotide", "b": "lanreotide", "title": "Octreotide vs lanreotide", "summary": "Octreotide and lanreotide are FDA approved somatostatin analogs that act on the same receptors (subtypes 2 and 5) and perform similarly in acromegaly, so the choice usually depends on formulation, tumor type, and cost. Octreotide offers short acting injections, a monthly intramuscular depot, and an oral capsule, and its PROMID trial slowed midgut neuroendocrine tumor growth (hazard ratio 0.34). Lanreotide is a monthly deep subcutaneous injection that patients can give at home, and its larger CLARINET trial covered both intestinal and pancreatic neuroendocrine tumors (hazard ratio 0.47).", "verdict": { "winner": "depends", "rationale": "Both have human RCT evidence and full FDA approval, and in the acromegaly meta-analysis their hormone control rates were in the same range (octreotide LAR about 57% for growth hormone and 67% for IGF-1, lanreotide about 48% and 47%, across heterogeneous studies). Octreotide is more flexible (subcutaneous, depot, and oral forms) and has cheaper generic short acting versions. Lanreotide's CLARINET evidence extends to pancreatic neuroendocrine tumors and higher Ki-67 grade 2 tumors, while PROMID studied midgut tumors only, and its prefilled syringe allows self injection. No large randomized head-to-head trial is cited here.", "source_ids": [ "freda-2005", "promid-2009", "clarinet-2014", "fda-sandostatin-label", "fda-somatuline-label" ] }, "dimensions": [ { "name": "Formulations", "a": "Subcutaneous injection two to four times daily (Sandostatin, Bynfezia), intramuscular depot every 4 weeks (Sandostatin LAR), and oral delayed release capsules (Mycapssa).", "b": "Deep subcutaneous depot every 4 weeks (Somatuline Depot, generic lanreotide), with extended 6 to 8 week intervals possible in controlled acromegaly.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] }, { "name": "Neuroendocrine tumor trial", "a": "PROMID (85 patients, midgut tumors, LAR 30 mg monthly): median time to progression 14.3 versus 6.0 months, hazard ratio 0.34.", "b": "CLARINET (204 patients, enteropancreatic grade 1 or 2 tumors with Ki-67 under 10%, 120 mg monthly): progression free survival hazard ratio 0.47; 65.1% versus 33.0% progression free at 24 months.", "note": "The trials enrolled different tumor populations, so the hazard ratios should not be compared directly. Neither showed an overall survival difference.", "source_ids": [ "promid-2009", "clarinet-2014" ] }, { "name": "Acromegaly control", "a": "Octreotide LAR normalized growth hormone in about 57% and IGF-1 in about 67% of patients in the pooled analysis.", "b": "Lanreotide normalized growth hormone in about 48% and IGF-1 in about 47% of patients in the same pooled analysis.", "note": "The pooled studies differed in patient selection; octreotide results were higher in preselected responders.", "source_ids": [ "freda-2005" ] }, { "name": "FDA approvals", "a": "1988 (acromegaly, carcinoid tumors, VIPomas); LAR 1998; Bynfezia and Mycapssa 2020. Generic injection and depot available.", "b": "2007 (acromegaly), 2014 (gastroenteropancreatic neuroendocrine tumors), 2017 (carcinoid syndrome). Generic approved December 2021.", "note": "Lanreotide carries a labeled antiproliferative indication for GEP-NETs; octreotide's antitumor use rests on PROMID and guidelines.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] }, { "name": "Gastrointestinal and gallbladder effects", "a": "Diarrhea, nausea, abdominal pain, and steatorrhea in up to 30 to 60% in acromegaly trials; gallstones or sludge in up to about half on long term treatment, mostly asymptomatic.", "b": "Diarrhea 26% versus 9% placebo and cholelithiasis 10% versus 3% in CLARINET; abdominal pain 14%.", "source_ids": [ "lamberts-1996", "clarinet-2014" ] }, { "name": "Administration", "a": "LAR is a deep intramuscular gluteal injection given in clinic; short acting forms are self injected several times daily.", "b": "Prefilled syringe for deep subcutaneous injection into the upper outer buttock, which the Somatuline Depot label says is intended for administration by a healthcare provider.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] }, { "name": "Typical cost", "a": "Generic subcutaneous octreotide roughly 200 to 800 USD per month cash; Sandostatin LAR roughly 4,000 to 8,000 USD per injection at list.", "b": "Somatuline Depot roughly 6,000 to 9,000 USD per injection at list; generic lanreotide lower but still several thousand USD.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is lanreotide better than octreotide for neuroendocrine tumors?", "a": "They have not been compared in a large randomized trial. Each beat placebo in its own trial, PROMID for midgut tumors and CLARINET for intestinal and pancreatic tumors, but the populations differed. Guidelines treat them as broadly interchangeable, with the choice driven by tumor site, formulation, and coverage.", "source_ids": [ "promid-2009", "clarinet-2014" ] }, { "q": "Can I switch between them?", "a": "Both act on somatostatin receptors 2 and 5, and their labels support monthly maintenance dosing, so switching is common in practice, for example to move from a clinic intramuscular injection to home subcutaneous injections. The prescriber sets the equivalent dose and monitors hormone levels or tumor response.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] }, { "q": "Is there an oral option?", "a": "Only for octreotide. Mycapssa oral delayed release capsules were approved in 2020 for acromegaly maintenance. Lanreotide is injection only.", "source_ids": [ "fda-sandostatin-label" ] }, { "q": "What side effects do they share?", "a": "Both commonly cause diarrhea, abdominal pain, and gallstones or biliary sludge, can raise or lower blood sugar, and can slow heart rate. In CLARINET, diarrhea affected 26% and gallstones 10% of lanreotide patients.", "source_ids": [ "lamberts-1996", "clarinet-2014", "fda-somatuline-label" ] }, { "q": "Are they available from compounding pharmacies or peptide clinics?", "a": "No. Both are FDA approved with generic versions, so compounding is limited to patient specific exceptions. They are prescribed by endocrinologists and oncologists and dispensed through specialty pharmacies or given in clinic.", "source_ids": [ "fda-sandostatin-label", "fda-somatuline-label" ] } ], "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": "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": "fda-sandostatin-label", "type": "fda", "title": "FDA prescribing information for Sandostatin and Sandostatin LAR (octreotide acetate), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=sandostatin" }, { "id": "fda-somatuline-label", "type": "fda", "title": "FDA prescribing information for Somatuline Depot (lanreotide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=somatuline" } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2 }, { "slug": "p21-vs-dihexa", "a": "p21", "b": "dihexa", "title": "P21 vs Dihexa", "summary": "Neither P21 nor dihexa has ever been tested in people, neither has a lawful US source, and both are prohibited in sport as non-approved substances. P21 has the cleaner record: its mouse studies, including a 12 month Alzheimer model study, have no retractions. Dihexa's mechanism paper was retracted in 2025 and its main rat study carries an expression of concern.", "verdict": { "winner": "a", "rationale": "Both are graded animal only and both come from single research groups, so neither is a supported choice for human use. P21 wins on the quality of the animal record: normal mice showed better memory and dentate gyrus neurogenesis, and 12 months of oral dosing in 3xTg-AD mice reduced tau pathology and soluble amyloid beta, with no integrity flags. Dihexa's HGF/c-Met mechanism paper was retracted and its design paper is under an expression of concern. On regulation they are equivalent: neither can lawfully be compounded.", "source_ids": [ "li-2010", "kazim-2014", "benoist-2014-retracted", "mccoy-2013", "fda-cat2" ] }, "dimensions": [ { "name": "What it is", "a": "Adamantane modified tetrapeptide derived from the active region of ciliary neurotrophic factor (CNTF).", "b": "Synthetic oligopeptide derived from angiotensin IV.", "source_ids": [ "li-2010", "mccoy-2013" ] }, { "name": "Proposed mechanism", "a": "CNTF mimetic that inhibits LIF signaling and raises BDNF, promoting neurogenesis and synaptic plasticity in mice.", "b": "Reported to potentiate hepatocyte growth factor and c-Met signaling; the supporting paper was retracted in 2025.", "source_ids": [ "li-2010", "kazim-2016", "benoist-2014-retracted" ] }, { "name": "Animal evidence", "a": "Better learning, memory, and neurogenesis in normal mice; 12 months of oral dosing in 3xTg-AD mice reduced tau hyperphosphorylation and soluble amyloid beta and rescued cognition.", "b": "Reversed scopolamine induced water maze deficits and improved aged rat performance in one laboratory's studies.", "source_ids": [ "li-2010", "kazim-2014", "mccoy-2013" ] }, { "name": "Data integrity", "a": "No retractions or expressions of concern identified; single research group.", "b": "Mechanism paper retracted (April 2025); design paper under a 2021 expression of concern; single research group.", "source_ids": [ "kazim-2016", "benoist-2014-retracted", "mccoy-2013" ] }, { "name": "Theoretical safety concern", "a": "A growth factor mimetic could in theory influence tumor growth; not studied.", "b": "Potentiating c-Met, an established oncogene, could promote tumor growth; no toxicology published.", "source_ids": [ "kazim-2016", "wright-harding-2015" ] }, { "name": "Human evidence", "a": "None. No trial registration, pharmacokinetic study, or safety report.", "b": "None. No human study of any kind.", "source_ids": [ "kazim-2016", "mccoy-2013" ] }, { "name": "FDA and compounding status", "a": "Never nominated for the 503A or 503B bulks lists and not on the Category 2 page; not compoundable.", "b": "Nominated and placed in Category 2, then withdrawn; not on the bulks list and not recommended by PCAC; not compoundable.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "name": "WADA status", "a": "Prohibited at all times under S0 (non-approved substances).", "b": "Prohibited at all times under S0 (non-approved substances).", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is P21 or dihexa better for memory?", "a": "Neither has been tested in humans. In mice, P21 improved memory and neurogenesis and reduced Alzheimer type pathology over 12 months; dihexa improved rat water maze performance in studies whose mechanism paper was later retracted. Neither result can be assumed to apply to people.", "source_ids": [ "li-2010", "kazim-2014", "mccoy-2013", "benoist-2014-retracted" ] }, { "q": "Can either be prescribed or compounded?", "a": "No. P21 has never been nominated for the bulks lists, and dihexa's nomination was withdrawn without a bulks list recommendation, so neither has a lawful basis for 503A or 503B compounding. Research chemical products are not lawful for human use.", "source_ids": [ "fda-cat2", "fda-compounding-qa" ] }, { "q": "Is there any human safety data?", "a": "No. Neither has a published human study, and neither has a published formal animal toxicology study. Both have theoretical concerns tied to growth factor signaling.", "source_ids": [ "kazim-2016", "wright-harding-2015" ] }, { "q": "Are they banned in sport?", "a": "Yes. Both are prohibited at all times under S0 of the WADA Prohibited List as non-approved substances.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "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": "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-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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "pinealon-vs-epitalon", "a": "pinealon", "b": "epitalon", "title": "Pinealon vs epitalon", "summary": "Pinealon (Glu-Asp-Arg) and epitalon (Ala-Glu-Asp-Gly) are short synthetic peptides from the same St. Petersburg institute. Pinealon is pitched for the brain and rests on rat and cell studies showing less oxidative damage in neurons. Epitalon is pitched for aging and has more data: telomerase activation in human cells, a lifelong mouse study with fewer tumors, and non-randomized human reports mostly of a related pineal extract. Neither has a randomized human trial or an FDA approval. Epitalon awaits an FDA final rule after a July 2026 advisory vote; pinealon has no lawful path.", "verdict": { "winner": "b", "rationale": "Epitalon has the larger and more varied evidence base (human cell, lifelong mouse, and observational human reports) and a regulatory path in progress: FDA removed it from Category 2 in April 2026 and its advisory committee recommended it for the 503A bulks list in July 2026. Pinealon has only rat and cell work from its developers and has never been nominated for compounding. The edge is relative: both are graded animal-only, neither is proven to help people, and epitalon still has no lawful compounded supply until FDA publishes a final rule.", "source_ids": [ "khavinson-2003-telomerase", "anisimov-2003", "khavinson-2003-human", "arutjunyan-2012", "fda-pcac-2026", "fda-category-2" ] }, "dimensions": [ { "name": "Structure", "a": "Tripeptide Glu-Asp-Arg (EDR), a Khavinson short peptide bioregulator.", "b": "Tetrapeptide Ala-Glu-Asp-Gly (AEDG), a synthetic version of the bovine pineal extract Epithalamin.", "source_ids": [ "khavinson-2020", "khavinson-2003-telomerase" ] }, { "name": "Proposed mechanism", "a": "Limits reactive oxygen species and necrotic death in neurons and other cells under oxidative stress; developers propose it also acts on gene expression linked to Alzheimer's disease.", "b": "Induces telomerase and lengthens telomeres in human cell cultures, through telomerase upregulation or the alternative lengthening pathway depending on the cell line.", "source_ids": [ "khavinson-2011", "khavinson-2020", "khavinson-2003-telomerase", "al-dulaimi-2025" ] }, { "name": "Animal evidence", "a": "Rats with prenatal hyperhomocysteinemia: offspring of treated mothers had better spatial learning and fewer necrotic cerebellar neurons.", "b": "Lifelong study in female mice: some aging biomarkers slowed, the longest lived 10% lived longer, and spontaneous tumors fell, but mean life span did not change significantly.", "source_ids": [ "arutjunyan-2012", "anisimov-2003" ] }, { "name": "Human evidence", "a": "No controlled human trial. A Russian language review from the developers describes use of peptide bioregulators in people of various ages without trial detail.", "b": "No randomized trial. Open, non-randomized follow up of elderly patients over 6 to 12 years, mostly with the pineal extract Epithalamin, reported lower mortality than untreated controls.", "source_ids": [ "umnov-2013", "khavinson-2003-human" ] }, { "name": "Independent replication", "a": "No independent replication identified; the studies cited here all come from the developing group.", "b": "An independent UK laboratory reported telomere lengthening in human cell lines in 2025; no independent animal or human outcome study.", "source_ids": [ "arutjunyan-2012", "khavinson-2011", "khavinson-2020", "al-dulaimi-2025" ] }, { "name": "FDA and compounding status", "a": "Never nominated for the 503A or 503B bulks lists and not an approved drug, so a 503A pharmacy has no lawful basis to compound it.", "b": "Removed from 503A Category 2 in April 2026 and recommended for the 503A bulks list by the advisory committee in July 2026; not lawful to compound from bulk until FDA publishes a final rule.", "source_ids": [ "fda-category-2", "fda-compounding-qa", "fda-pcac-2026", "fda-503a-bulks" ] }, { "name": "Dosing", "a": "No human dose established; supplement labeling in Russia is not based on a dose finding study.", "b": "No human dose established; no human pharmacokinetic or dose ranging study has been published.", "source_ids": [ "umnov-2013", "khavinson-2003-human" ] }, { "name": "Safety", "a": "No human safety data of any kind.", "b": "No systematic human safety data; telomerase activation raises a theoretical question about existing tumors, although the mouse study found fewer tumors.", "source_ids": [ "arutjunyan-2012", "anisimov-2003" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S0 (non-approved substances).", "b": "Prohibited at all times under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "No lawful price. Not available through licensed US channels; research chemical listings are not lawful for human use.", "b": "No lawful compounded price until FDA publishes a final rule; advertised clinic prices are not a comparable price.", "source_ids": [ "fda-compounding-qa", "fda-pcac-2026" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Are pinealon and epitalon the same thing?", "a": "No. Both are short synthetic peptides from the same St. Petersburg research group, but pinealon is three amino acids (Glu-Asp-Arg) aimed at the brain, and epitalon is four (Ala-Glu-Asp-Gly) modeled on a pineal gland extract and aimed at aging.", "source_ids": [ "khavinson-2020", "khavinson-2003-telomerase" ] }, { "q": "Which has better evidence?", "a": "Epitalon, though neither is strong. Epitalon has human cell studies, a lifelong mouse study, and non-randomized human reports. Pinealon has rat and cell studies only. Neither has a randomized human trial.", "source_ids": [ "khavinson-2003-telomerase", "anisimov-2003", "khavinson-2003-human", "arutjunyan-2012", "khavinson-2011" ] }, { "q": "Does epitalon lengthen telomeres in people?", "a": "That has not been shown. Telomerase activation and telomere lengthening were measured in cultured human cells, not in people, and no human trial has measured telomere length after epitalon.", "source_ids": [ "khavinson-2003-telomerase", "al-dulaimi-2025" ] }, { "q": "Can either be prescribed legally in the US?", "a": "Not yet. Epitalon was recommended for the 503A bulks list in July 2026, but a pharmacy has no federal basis to compound it from bulk until FDA publishes a final rule. Pinealon has never been nominated and has no lawful path.", "source_ids": [ "fda-pcac-2026", "fda-503a-bulks", "fda-category-2" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are unapproved substances prohibited at all times under WADA section S0.", "source_ids": [ "wada-list" ] } ], "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-2011", "type": "pubmed", "title": "Khavinson V et al. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Rejuvenation Res 2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21978084/", "pmid": "21978084", "year": 2011 }, { "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": "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-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" }, { "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Pinealon vs epitalon (epithalon): evidence compared" } }, { "slug": "pt-141-vs-melanotan-ii", "a": "pt-141", "b": "melanotan-ii", "title": "PT-141 (bremelanotide) vs Melanotan II", "summary": "PT-141 is the clear choice: as bremelanotide (Vyleesi) it is FDA approved for low sexual desire in premenopausal women on the strength of two phase 3 trials with 1,267 women, and it can be prescribed and compounded lawfully. Melanotan II, the parent compound that PT-141 is derived from, was tested in only two 10 man erectile dysfunction studies, has never been approved anywhere, and has a trail of case reports including priapism, eruptive moles, and renal infarction. PT-141 does not tan in any meaningful way; Melanotan II is sold mainly as an unlawful tanning injection.", "verdict": { "winner": "a", "rationale": "PT-141 is FDA approved and graded human RCT from the RECONNECT phase 3 program, though the effect on desire is small (0.30 to 0.42 points on the FSFI desire domain) and its clinical meaningfulness has been questioned. Melanotan II is also graded human RCT, but only from two tiny crossover trials in the 1990s, and it has no approved use, no lawful compounding basis after its Category 2 nomination was withdrawn, and published case reports of serious harm. Both act on melanocortin receptors, but only one has a regulated product, a label, and phase 3 safety data.", "source_ids": [ "kingsberg-2019", "spielmans-2024", "vyleesi-label", "wessells-1998", "wessells-2000", "fda-cat2" ] }, "dimensions": [ { "name": "What it is", "a": "Cyclic heptapeptide MC4R and MC3R agonist; an active metabolite of Melanotan II.", "b": "Cyclic heptapeptide alpha-MSH analog; nonselective agonist at MC1R, MC3R, MC4R, and MC5R.", "source_ids": [ "vyleesi-label", "wessells-1998" ] }, { "name": "Receptor profile and effects", "a": "Acts centrally on MC4R and MC3R to increase sexual desire; only minor MC1R effects (focal hyperpigmentation in about 1%).", "b": "Strong MC1R activation causes tanning and darkening of moles, while MC4R activation causes erections, reduced appetite, and yawning.", "source_ids": [ "vyleesi-label", "wessells-1998", "schulze-2014" ] }, { "name": "Human evidence", "a": "Two phase 3 randomized trials (RECONNECT, 1,267 premenopausal women, 24 weeks) plus a 52 week extension; smaller intranasal trials in men, including sildenafil non-responders.", "b": "Two double-blind crossover trials of 10 men each with erectile dysfunction (1998, 2000): erections in 8 of 10 men and after 12 of 19 injections versus 1 of 21 placebo doses. No tanning trial.", "source_ids": [ "kingsberg-2019", "simon-2019", "safarinejad-2008", "wessells-1998", "wessells-2000" ] }, { "name": "Effect size", "a": "Desire rose 0.30 and 0.42 points versus placebo and distress fell 0.37 and 0.29 points; a 2024 reanalysis argued these changes are below thresholds for clinical meaningfulness.", "b": "Tip rigidity above 80% lasted 38 minutes versus 3 minutes with placebo in psychogenic erectile dysfunction.", "source_ids": [ "kingsberg-2019", "spielmans-2024", "wessells-1998" ] }, { "name": "Safety", "a": "Nausea in about 40%, flushing about 20%, headache about 11%; transient blood pressure rise of about 6 mmHg systolic after each dose; label limits use to 8 doses per month.", "b": "Severe nausea after 4 of 19 injections in trials; case reports of eruptive and darkening moles within 24 hours, priapism, renal infarction, and FDA cited reports of melanoma and posterior reversible encephalopathy syndrome.", "source_ids": [ "vyleesi-label", "wessells-2000", "schulze-2014", "dreyer-2019", "peters-2020", "fda-cat2" ] }, { "name": "FDA status", "a": "FDA approved as Vyleesi (June 2019) for acquired, generalized hypoactive sexual desire disorder in premenopausal women; use in men is off label.", "b": "Not approved in any country. Its Category 2 nomination was withdrawn, but it is not on the bulks list and not an approved drug component, so a 503A pharmacy has no basis to compound it.", "source_ids": [ "vyleesi-label", "fda-cat2" ] }, { "name": "Dosing in the label or literature", "a": "Vyleesi: 1.75 mg subcutaneously at least 45 minutes before sexual activity, no more than once in 24 hours or 8 times per month.", "b": "Single 0.025 mg/kg subcutaneous doses in the two trials; no repeat dose or tanning regimen has been studied.", "source_ids": [ "vyleesi-label", "wessells-1998" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited at all times under S0 (non-approved substances).", "source_ids": [ "wada-list", "wada-list-s0" ] }, { "name": "Cost and access", "a": "Vyleesi list price roughly 900 USD per carton of four autoinjectors, about 99 USD with a copay program for commercially insured patients; compounded PT-141 roughly 100 to 300 USD per vial or spray.", "b": "No lawful channel. Gray market tanning vials have been found unsterile or mislabeled.", "source_ids": [ "vyleesi-label", "fda-compounding-qa", "fda-cat2" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is PT-141 the same as Melanotan II?", "a": "No, but they are related. Bremelanotide (PT-141) is an active metabolite of Melanotan II that was developed separately and approved as Vyleesi. It acts mainly on the brain receptors involved in desire, while Melanotan II also strongly activates the skin pigment receptor.", "source_ids": [ "vyleesi-label", "wessells-1998" ] }, { "q": "Which works better for erectile dysfunction?", "a": "Neither is approved for men. Both produced erections in small placebo controlled trials, including intranasal PT-141 in men who had failed sildenafil. PDE5 inhibitors remain the standard, and PT-141 use in men is off label.", "source_ids": [ "safarinejad-2008", "diamond-2004", "wessells-2000" ] }, { "q": "Will PT-141 give me a tan like Melanotan II?", "a": "No meaningful tan. The Vyleesi label reports focal darkening of the face, gums, or breasts in about 1% of users, more often with frequent dosing. Melanotan II causes whole body tanning and can darken moles or cause new ones within a day.", "source_ids": [ "vyleesi-label", "schulze-2014" ] }, { "q": "Is Melanotan II legal?", "a": "Not for human use in the United States. It is not approved anywhere, and although its Category 2 nomination was withdrawn, it is not on the 503A bulks list or a component of an approved drug, so pharmacies have no basis to compound it. FDA has cited case reports of melanoma, encephalopathy, and priapism.", "source_ids": [ "fda-cat2", "dreyer-2019" ] }, { "q": "What are the main risks of PT-141?", "a": "Nausea is the most common effect (about 40% in trials, mostly after the first dose), followed by flushing and headache. Blood pressure rises briefly after each dose, so it is not for people with uncontrolled hypertension or cardiovascular disease, and it lowers absorption of oral naltrexone.", "source_ids": [ "vyleesi-label", "kingsberg-2019" ] } ], "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": "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/search.cfm?labeltype=all&query=vyleesi", "year": 2025 }, { "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": "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": "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": "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": "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "id": "wada-list-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list", "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": "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 2, "seo": { "title": "PT-141 vs Melanotan II (MT2): evidence and safety" } }, { "slug": "pt-141-vs-oxytocin", "a": "pt-141", "b": "oxytocin", "title": "PT-141 vs oxytocin", "summary": "For low sexual desire, the reason people compare these two, PT-141 (bremelanotide) is the only one with an FDA indication and randomized trial evidence: two 24 week phase 3 trials in 1,267 premenopausal women with hypoactive sexual desire disorder showed statistically significant, if small, gains in desire. Intranasal oxytocin's only sexual function trial, a crossover in 29 couples, found no effect on desire, arousal, erection, or lubrication. Oxytocin's approval and strong evidence are for labor and postpartum bleeding, not for anything a peptide clinic prescribes it for.", "verdict": { "winner": "a", "rationale": "PT-141 wins for the sexual desire use case on both evidence and regulatory grounds: it is FDA approved as Vyleesi for premenopausal women with acquired, generalized hypoactive sexual desire disorder on the strength of the RECONNECT trials, even though an independent reanalysis argues the effect sizes (0.30 to 0.42 points on the desire domain) are below clinical meaningfulness. Oxytocin is FDA approved only as an obstetric injectable; its intranasal use rests on one negative crossover study for sexual function and on mixed meta-analyses in autism. Neither is approved for men, and PT-141's intranasal male program was abandoned over blood pressure effects.", "source_ids": [ "kingsberg-2019", "spielmans-2024", "vyleesi-label", "behnia-2014", "pitocin-label" ] }, "dimensions": [ { "name": "Evidence for sexual function", "a": "Two identical 24 week randomized, double-blind, placebo-controlled phase 3 trials (n = 1,267 premenopausal women): FSFI desire domain rose 0.30 and 0.42 points versus placebo and distress fell 0.37 and 0.29 points. In men, small phase 1 and 2 intranasal studies showed erectile responses, including in sildenafil non-responders.", "b": "One double-blind, placebo-controlled crossover study of intranasal oxytocin 24 IU in 29 healthy couples: no change in sexual drive, arousal, erection, or lubrication; small to moderate increases in orgasm intensity and post-sex contentment, larger in men.", "source_ids": [ "kingsberg-2019", "diamond-2004", "safarinejad-2008", "behnia-2014" ] }, { "name": "How meaningful the effect is", "a": "Statistically significant but questioned: a 2024 critical reanalysis argues the desire and distress changes fall below thresholds for clinical meaningfulness.", "b": "No effect on the primary sexual function measures; the secondary orgasm and contentment findings came from a single small study and have not been replicated.", "source_ids": [ "spielmans-2024", "behnia-2014" ] }, { "name": "FDA approved indication", "a": "Vyleesi, approved June 21, 2019, for premenopausal women with acquired, generalized hypoactive sexual desire disorder. Not indicated for postmenopausal women or men.", "b": "Pitocin and generics, approved for labor induction and augmentation and for control of postpartum bleeding. No intranasal oxytocin product is FDA approved in the United States.", "source_ids": [ "vyleesi-label", "pitocin-label" ] }, { "name": "Mechanism", "a": "Melanocortin receptor agonist (mainly MC4R, also MC3R) acting in hypothalamic circuits for sexual arousal and appetite; also stimulates MC1R on melanocytes, which explains focal skin darkening.", "b": "Binds the oxytocin receptor on uterine and mammary smooth muscle and on limbic and hypothalamic neurons involved in bonding and stress. Peripheral oxytocin crosses the blood brain barrier poorly, and how much intranasal oxytocin reaches central receptors in humans is debated.", "source_ids": [ "vyleesi-label", "pitocin-label", "huang-2021" ] }, { "name": "Route and dosing from labels and trials", "a": "1.75 mg subcutaneously by autoinjector at least 45 minutes before anticipated sexual activity, no more than one dose in 24 hours and no more than eight doses per month.", "b": "Obstetric use is intravenous infusion or intramuscular injection under the Pitocin label. Research nasal sprays used 24 IU as a single dose; there is no established intranasal dose for sexual function.", "source_ids": [ "vyleesi-label", "pitocin-label", "behnia-2014" ] }, { "name": "Side effects", "a": "Nausea in about 40% (13% needed an antiemetic), flushing about 20%, injection site reactions about 13%, headache about 11%, a transient rise in blood pressure of about 6 mmHg systolic with a fall in heart rate after each dose, and focal hyperpigmentation in about 1%.", "b": "Injectable: uterine hyperstimulation, fetal distress, water intoxication with hyponatremia after prolonged high dose infusion, hypotension after rapid bolus. Intranasal: nasal irritation, headache, drowsiness; long term safety of repeated nasal dosing is not established.", "source_ids": [ "vyleesi-label", "kingsberg-2019", "pitocin-label" ] }, { "name": "Regulatory and compounding status", "a": "Approved drug. Some 503A pharmacies compound bremelanotide vials and nasal sprays under the approved drug component pathway; those formulations are not FDA approved and the nasal route was abandoned by the sponsor.", "b": "Approved injectable. 503A pharmacies may compound oxytocin nasal sprays or lozenges under a prescription because it is a component of an approved drug; these products are not FDA approved and have not been shown to reach meaningful brain levels.", "source_ids": [ "vyleesi-label", "fda-compounding-qa", "pitocin-label" ] }, { "name": "Typical cost", "a": "Vyleesi list price roughly 900 USD per carton of four autoinjectors, with a manufacturer copay program near 99 USD per carton for commercially insured patients. Compounded PT-141 through telehealth typically 100 to 300 USD per vial or spray.", "b": "Generic oxytocin injection costs a few USD per vial. Compounded intranasal oxytocin through telehealth or peptide clinics typically 50 to 150 USD per month.", "note": "Prices verified on the last verified date and change often.", "source_ids": [ "vyleesi-label", "pitocin-label", "fda-compounding-qa" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not on the WADA Prohibited List.", "note": "Neither is prohibited in sport.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which works better for low libido, PT-141 or oxytocin?", "a": "PT-141 has the evidence. Two phase 3 trials in 1,267 premenopausal women showed small but statistically significant gains in desire and reductions in distress, and it is FDA approved for that use. Intranasal oxytocin showed no effect on sexual drive or arousal in its one placebo-controlled crossover study in couples.", "source_ids": [ "kingsberg-2019", "behnia-2014", "vyleesi-label" ] }, { "q": "Is either one approved for men?", "a": "No. Vyleesi is indicated only for premenopausal women, and PT-141's intranasal program in men with erectile dysfunction was discontinued over blood pressure increases despite positive small studies. Oxytocin's approvals are obstetric. Any use in men is off-label.", "source_ids": [ "vyleesi-label", "diamond-2004", "safarinejad-2008", "pitocin-label" ] }, { "q": "How large is PT-141's effect?", "a": "Modest. The desire domain improved by 0.30 and 0.42 points versus placebo in the two trials, and a 2024 reanalysis argues those changes are below the threshold for clinical meaningfulness. About 40% of treated women had nausea.", "source_ids": [ "kingsberg-2019", "spielmans-2024", "vyleesi-label" ] }, { "q": "Does nasal oxytocin actually reach the brain?", "a": "Uncertain. Peripheral oxytocin crosses the blood brain barrier poorly, intranasal delivery is proposed to reach the brain through olfactory and trigeminal pathways, and how much reaches central receptors in humans is debated. Meta-analyses in autism show benefit on social functioning but not on non-social symptoms, and no nasal product is FDA approved.", "source_ids": [ "huang-2021", "pitocin-label", "fda-compounding-qa" ] }, { "q": "Which has the more serious safety concerns?", "a": "PT-141 raises blood pressure transiently after each dose and is contraindicated in uncontrolled hypertension or known cardiovascular disease; it also slows gastric emptying enough to reduce absorption of oral naltrexone. Injectable oxytocin's serious risks are obstetric. For compounded nasal oxytocin the main concern is the absence of long term safety data rather than a known harm.", "source_ids": [ "vyleesi-label", "pitocin-label" ] } ], "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": "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": "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": "vyleesi-label", "type": "fda", "title": "FDA prescribing information for Vyleesi (bremelanotide injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=vyleesi", "year": 2025 }, { "id": "pitocin-label", "type": "fda", "title": "FDA prescribing information for Pitocin (oxytocin injection), via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=pitocin", "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": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "retatrutide-vs-mazdutide", "a": "retatrutide", "b": "mazdutide", "title": "Retatrutide vs mazdutide", "summary": "Retatrutide has produced the larger weight loss: 28.3% at 12 mg over 80 weeks in the TRIUMPH-1 phase 3 trial (manufacturer topline), versus 14.0% at 6 mg over 48 weeks for mazdutide in GLORY-1 and 18.1% at 16 mg over 32 weeks in a US phase 2 trial. Mazdutide, however, is approved in China for weight management and type 2 diabetes, while retatrutide is not approved anywhere. Neither can lawfully be obtained in the United States outside a trial.", "verdict": { "winner": "depends", "rationale": "On efficacy, retatrutide's phase 3 weight loss is roughly double mazdutide's at the doses tested so far, though no trial compares them and TRIUMPH-1 is reported only in a press release. On regulatory standing, mazdutide is ahead because China's regulator has approved it. For a US reader both are trial-only drugs, so the comparison matters mostly for following the pipeline.", "source_ids": [ "triumph-1-topline", "glory-1", "mazdutide-us-phase2", "mazdutide-china-obesity-approval", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Mechanism", "a": "Triple agonist of the GIP, GLP-1, and glucagon receptors.", "b": "Dual agonist of the GLP-1 and glucagon receptors (oxyntomodulin analog).", "note": "Both use glucagon receptor activity to raise energy expenditure; retatrutide adds GIP receptor activity.", "source_ids": [ "retatrutide-phase2-obesity", "glory-1" ] }, { "name": "Best weight loss evidence", "a": "TRIUMPH-1 (2,339 adults, 80 weeks): 19.0%, 25.9%, and 28.3% at 4, 9, and 12 mg versus 2.2% on placebo (efficacy estimand), per manufacturer topline results.", "b": "GLORY-1 (610 Chinese adults, 48 weeks): 11.0% and 14.0% at 4 and 6 mg versus 0.3% gain on placebo. US phase 2 (179 adults, 32 weeks): up to 18.1% at 16 mg.", "source_ids": [ "triumph-1-topline", "glory-1", "mazdutide-us-phase2" ] }, { "name": "Type 2 diabetes evidence", "a": "TRANSCEND-T2D-1 phase 3 (537 adults, 40 weeks) showed significant HbA1c and weight improvement; TRIUMPH-2 reported up to 20.8% weight loss in obesity with type 2 diabetes (topline).", "b": "DREAMS-2 phase 3 (731 adults, 28 weeks): HbA1c 0.24 to 0.30 points and weight 3.8% to 5.8% lower than dulaglutide 1.5 mg.", "source_ids": [ "transcend-t2d-1", "triumph-2-3-topline", "dreams-2" ] }, { "name": "Tolerability", "a": "TRIUMPH-1: nausea 28.6% to 42.4% versus 14.8% on placebo; discontinuation for adverse events 11.3% at 12 mg versus 4.9%.", "b": "GLORY-1: discontinuation for adverse events 1.5% or less; the diabetes phase 2 trial reported diarrhea in 36% and nausea in 23%.", "source_ids": [ "triumph-1-topline", "glory-1", "mazdutide-t2d-phase2" ] }, { "name": "Regulatory status", "a": "Investigational; not approved by FDA or any other regulator, not eligible for compounding.", "b": "Approved in China (weight management June 2025, type 2 diabetes September 2025). Not FDA approved and not eligible for US compounding.", "source_ids": [ "fda-503a-bulks", "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval" ] }, { "name": "WADA status", "a": "Prohibited under section S0 (non-approved substances).", "b": "Not named on the list; with approval in China, section S0 may not apply. Athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list", "mazdutide-china-obesity-approval" ] }, { "name": "Trial doses", "a": "Once weekly 4, 9, or 12 mg in phase 3.", "b": "Once weekly 4 or 6 mg in GLORY-1; 3 to 16 mg in the US phase 2 trial.", "source_ids": [ "triumph-1-topline", "glory-1", "mazdutide-us-phase2" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which causes more weight loss, retatrutide or mazdutide?", "a": "Retatrutide in the trials reported so far: 28.3% at 12 mg over 80 weeks in TRIUMPH-1 versus 14.0% at 6 mg over 48 weeks for mazdutide in GLORY-1. There is no head-to-head trial, and higher mazdutide doses (up to 16 mg) are still in development.", "source_ids": [ "triumph-1-topline", "glory-1", "mazdutide-us-phase2" ] }, { "q": "Is either one approved?", "a": "Mazdutide is approved in China for chronic weight management and type 2 diabetes. Retatrutide is not approved anywhere. Neither is FDA approved.", "source_ids": [ "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval", "fda-503a-bulks" ] }, { "q": "Can I buy retatrutide or mazdutide legally in the US?", "a": "No. Neither is FDA approved or on the 503A bulks list, so neither can be lawfully compounded or sold for human use. Products labeled research use only are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks", "fda-glp1-compounding" ] }, { "q": "Are they allowed in tested sport?", "a": "Retatrutide is prohibited under WADA section S0. Mazdutide's status is less clear because it is approved in China; athletes should ask their anti-doping organization before use.", "source_ids": [ "wada-list" ] } ], "sources": [ { "id": "triumph-1-topline", "type": "other", "title": "Manufacturer press release: retatrutide TRIUMPH-1 phase 3 topline results in obesity (May 21, 2026), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html", "year": 2026 }, { "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 randomised placebo-controlled trial. Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42628555/", "pmid": "42628555", "year": 2026 }, { "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), accessed 2026-09-22", "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": "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" }, { "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": "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-2-3-topline", "type": "other", "title": "Manufacturer press release: retatrutide TRIUMPH-2 and TRIUMPH-3 phase 3 topline results (July 23, 2026), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html", "year": 2026 }, { "id": "dreams-2", "type": "pubmed", "title": "Guo L et al. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature 2026 (DREAMS-2)", "url": "https://pubmed.ncbi.nlm.nih.gov/41407860/", "pmid": "41407860", "year": 2026 }, { "id": "mazdutide-t2d-phase2", "type": "pubmed", "title": "Zhang B et al. Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. Diabetes Care 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/", "pmid": "37943529", "year": 2024 }, { "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), accessed 2026-09-22", "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 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss (page updated September 1, 2026)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "retatrutide-vs-survodutide", "a": "retatrutide", "b": "survodutide", "title": "Retatrutide vs survodutide", "summary": "Retatrutide has produced much larger weight loss: 24.2% at 48 weeks on 12 mg in its phase 2 trial, versus 12.2% to 13.0% at 76 weeks for survodutide in the phase 3 SYNCHRONIZE-1 trial. Survodutide's distinctive evidence is in the liver, where up to 62% of people with biopsy proven MASH improved versus 14% on placebo. Neither is FDA approved, neither can be compounded, and both are prohibited in sport, so today the comparison matters only for clinical trial choices.", "verdict": { "winner": "a", "rationale": "On weight, retatrutide wins clearly: its phase 2 placebo adjusted loss (about 22 percentage points at 12 mg) is roughly three times survodutide's phase 3 placebo adjusted loss (about 7 to 8 points), although the trials differ in phase, length, and population. Both hold the human_rct grade and the same not_eligible regulatory status, and survodutide has stronger liver histology data. No trial has compared them directly and neither has reported cardiovascular outcomes.", "source_ids": [ "retatrutide-phase2-obesity", "synchronize-1", "survodutide-mash-phase2", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Mechanism", "a": "Triple agonist of the GIP, GLP-1, and glucagon receptors.", "b": "Dual agonist of the glucagon and GLP-1 receptors (no GIP activity).", "note": "Both use glucagon receptor activity to raise energy expenditure and liver fat oxidation.", "source_ids": [ "retatrutide-phase2-obesity", "synchronize-1" ] }, { "name": "Best weight loss evidence", "a": "Phase 2 (338 adults, 48 weeks): 8.7%, 17.1%, 22.8%, and 24.2% at 1, 4, 8, and 12 mg versus 2.1% on placebo.", "b": "Phase 3 SYNCHRONIZE-1 (725 adults, 76 weeks): 12.2% at 3.6 mg and 13.0% at 6.0 mg versus 5.4% on placebo.", "note": "Cross-trial comparison only; phase 3 obesity results for retatrutide (TRIUMPH) are still being reported.", "source_ids": [ "retatrutide-phase2-obesity", "synchronize-1", "triumph-design" ] }, { "name": "Liver disease evidence", "a": "No dedicated liver histology trial in the record; liver fat reduction is a secondary rationale for glucagon activity.", "b": "Phase 2 MASH trial (293 adults, 48 weeks): MASH improvement without worsening fibrosis in 47%, 62%, and 43% at 2.4, 4.8, and 6.0 mg versus 14% on placebo.", "source_ids": [ "retatrutide-phase2-obesity", "survodutide-mash-phase2" ] }, { "name": "Type 2 diabetes evidence", "a": "Phase 2 (281 adults, 36 weeks) against placebo and dulaglutide, and phase 3 TRANSCEND-T2D-1 (537 adults, 40 weeks) with significant HbA1c and weight improvement.", "b": "SYNCHRONIZE-1 excluded people with diabetes; the record has no published diabetes efficacy trial.", "source_ids": [ "retatrutide-phase2-t2d", "transcend-t2d-1", "synchronize-1" ] }, { "name": "Side effects", "a": "Dose related nausea, diarrhea, vomiting, and constipation; heart rate increase greater than GLP-1 only drugs; skin sensitivity and dysesthesia reported in phase 2.", "b": "Gastrointestinal symptoms in 80.9% (3.6 mg) and 89.7% (6.0 mg) versus 47.9% on placebo in SYNCHRONIZE-1; decreased appetite drove withdrawals during escalation in phase 1.", "source_ids": [ "retatrutide-phase2-obesity", "synchronize-1", "survodutide-phase1" ] }, { "name": "Trial doses", "a": "Once weekly, escalated every 4 weeks to 1, 4, 8, or 12 mg (phase 2 obesity); 4, 9, or 12 mg in phase 3 diabetes.", "b": "Once weekly, escalated over a prolonged period to 3.6 or 6.0 mg (SYNCHRONIZE-1); 2.4 to 6.0 mg in the MASH trial.", "note": "Trial regimens only; no approved label exists for either.", "source_ids": [ "retatrutide-phase2-obesity", "transcend-t2d-1", "synchronize-1", "survodutide-mash-phase2" ] }, { "name": "Regulatory and access status", "a": "Not approved by FDA or any other regulator; not on the 503A bulks list, so it cannot be compounded. Phase 3 TRIUMPH program ongoing.", "b": "Not approved by FDA or any other regulator; not on the 503A bulks list, so it cannot be compounded. Phase 3 SYNCHRONIZE program, including a cardiovascular outcomes trial, ongoing.", "note": "Both are prohibited in sport under WADA section S0.", "source_ids": [ "fda-503a-bulks", "triumph-design", "synchronize-design", "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which causes more weight loss, retatrutide or survodutide?", "a": "Retatrutide, based on published trials: 24.2% at 48 weeks on 12 mg in phase 2 versus 12.2% to 13.0% at 76 weeks for survodutide in phase 3. The trials are not directly comparable and no head-to-head trial exists.", "source_ids": [ "retatrutide-phase2-obesity", "synchronize-1" ] }, { "q": "Why is survodutide being studied for liver disease?", "a": "Glucagon receptor activation increases liver fat oxidation. In a 48 week phase 2 trial in biopsy confirmed MASH, 43% to 62% of treated participants improved without worsening fibrosis versus 14% on placebo.", "source_ids": [ "survodutide-mash-phase2" ] }, { "q": "Can I get either one legally?", "a": "Only in a registered clinical trial. Neither is FDA approved, neither is a component of an approved drug or on the 503A bulks list, so compounding pharmacies cannot lawfully make them, and products sold as research chemicals are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-glp1-compounding" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are prohibited at all times under WADA section S0, which covers substances not approved for human therapeutic use.", "source_ids": [ "wada-list" ] }, { "q": "What are the main side effects?", "a": "Mostly gastrointestinal for both. Survodutide caused gastrointestinal symptoms in 80.9% to 89.7% of participants versus 47.9% on placebo in SYNCHRONIZE-1. Retatrutide raised heart rate more than GLP-1 only drugs and caused skin sensitivity in some phase 2 participants.", "source_ids": [ "synchronize-1", "retatrutide-phase2-obesity" ] } ], "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": "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": "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "selank-vs-noopept", "a": "selank", "b": "noopept", "title": "Selank vs Noopept", "summary": "Selank and Noopept are both Russian medicines with only small open label human studies, and neither has a clear lawful US channel. Selank is an intranasal peptide studied for anxiety; it is off FDA Category 2 but was not recommended for the 503A bulks list, so few pharmacies compound it. Noopept is an oral piracetam relative studied for mild cognitive impairment; it cannot be compounded and is sold as a supplement ingredient, which is not an approved use.", "verdict": { "winner": "depends", "rationale": "They tie on evidence (both human observational, from open Russian studies without placebo control) and both lack a reliable lawful source, so the choice depends on the goal. Selank was studied for anxiety, including a comparison with phenazepam; Noopept was studied for cognitive impairment after stroke or brain injury, including a comparison with piracetam. For either goal, approved treatments with placebo controlled evidence should come first.", "source_ids": [ "zozulya-2008", "medvedev-2014", "neznamov-2009", "amelin-2011", "fda-503a-bulks", "fda-cat2" ] }, "dimensions": [ { "name": "What it is", "a": "Heptapeptide analog of the immune peptide tuftsin with a Pro-Gly-Pro tail.", "b": "Synthetic dipeptide-like piracetam relative metabolized to cycloprolylglycine.", "source_ids": [ "vyunova-2018", "ostrovskaya-2014" ] }, { "name": "Main use studied", "a": "Generalized anxiety disorder and neurasthenia.", "b": "Mild cognitive impairment of vascular or traumatic origin, including after stroke.", "source_ids": [ "zozulya-2008", "neznamov-2009", "amelin-2011" ] }, { "name": "Proposed mechanism", "a": "GABA-A modulation and inhibition of enkephalin degrading enzymes in rodent and cell work.", "b": "BDNF and NGF induction and alpha-7 nicotinic receptor effects on hippocampal interneurons in rodent work.", "source_ids": [ "vyunova-2018", "kondratenko-2022" ] }, { "name": "Active comparator studied", "a": "Phenazepam (a benzodiazepine): similar anxiety relief with less sedation reported, not placebo controlled.", "b": "Piracetam: broader and faster improvement reported, no placebo arm.", "source_ids": [ "medvedev-2014", "neznamov-2009" ] }, { "name": "Route and dose in the literature", "a": "Intranasal 0.15% solution, roughly 0.3 to 2.7 mg per day for 10 to 14 days.", "b": "Oral 10 mg twice daily (20 mg per day) for 2 months.", "source_ids": [ "zozulya-2008", "amelin-2011" ] }, { "name": "Theoretical interactions", "a": "Possible additive effects with benzodiazepines, alcohol, and other GABAergic drugs, and with opioids via enkephalinase inhibition (untested).", "b": "Possible additive effects with other nootropics, stimulants, or nicotinic drugs (untested).", "source_ids": [ "vyunova-2018", "kondratenko-2022" ] }, { "name": "FDA and compounding status", "a": "Nomination withdrawn, so no longer in Category 2, but not on the bulks list and not recommended by PCAC in July 2026; most 503A pharmacies will not compound it.", "b": "Never nominated; not compoundable under 503A or 503B. Sold as a supplement ingredient, which is not an approved use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "fda-cat2", "fda-compounding-qa" ] }, { "name": "Typical cost", "a": "No lawful compounded price: selank is not on the 503A bulks list and was not recommended by PCAC in July 2026.", "b": "Sold online as an unapproved supplement that is not verified for identity or purity; no licensed pharmacy or telehealth channel.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa" ] }, { "name": "WADA status", "a": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "b": "Not named on the WADA Prohibited List; status unclear, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Should I take selank or Noopept for anxiety?", "a": "Selank is the one studied for anxiety, in small Russian studies without placebo control. Noopept's human studies measured cognition, though anxiety scores also improved in the piracetam comparison. Neither has proven benefit by Western trial standards.", "source_ids": [ "zozulya-2008", "medvedev-2014", "neznamov-2009" ] }, { "q": "Which is better for cognition?", "a": "Noopept has the more relevant data: an open study of 60 stroke patients reported better MMSE scores after 2 months at 20 mg per day versus untreated controls. Selank's cognitive claims rest mostly on rodent work.", "source_ids": [ "amelin-2011", "vyunova-2018" ] }, { "q": "Can I get either from a US pharmacy?", "a": "Rarely. Selank is off Category 2 but not on the bulks list and was not recommended by the Pharmacy Compounding Advisory Committee, so most pharmacies will not compound it. Noopept has never been nominated and cannot be compounded.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "fda-cat2" ] }, { "q": "Is Noopept legal as a supplement?", "a": "It is widely sold that way, but it is a synthetic drug substance approved as a medicine in Russia and does not meet the definition of a dietary ingredient, so supplement sales are not an approved use.", "source_ids": [ "fda-compounding-qa" ] } ], "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": "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": "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-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": "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": "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-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": "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-cagrilintide", "a": "semaglutide", "b": "cagrilintide", "title": "Semaglutide vs cagrilintide", "summary": "Semaglutide is an FDA approved GLP-1 drug with proven weight loss (14.9% at 68 weeks in STEP 1) and cardiovascular benefit, while cagrilintide is an investigational amylin analog that produced 10.8% weight loss at 26 weeks in its only monotherapy trial. The two are not really rivals: they work through different pathways and are being developed together as CagriSema, which produced 20.4% weight loss in REDEFINE 1. As of September 2026 cagrilintide is not approved, cannot be compounded, and is prohibited in sport.", "verdict": { "winner": "a", "rationale": "Semaglutide wins on everything a patient can act on today: it is FDA approved for weight management and cardiovascular risk reduction, backed by STEP 1 and SELECT, and available by prescription. Cagrilintide has human_rct data but no approval, no lawful compounding pathway, and no long term safety or outcomes data; its main role is as an add-on to semaglutide, where REDEFINE 5 showed the combination beat semaglutide alone by 6.5 percentage points.", "source_ids": [ "step-1", "select", "fda-wegovy-label", "cagrilintide-phase2", "redefine-1", "redefine-5", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Mechanism", "a": "GLP-1 receptor agonist: glucose dependent insulin release, glucagon suppression, slower gastric emptying, reduced appetite.", "b": "Long acting amylin analog acting on amylin and calcitonin receptors in the area postrema and hypothalamus to increase satiety and slow gastric emptying.", "note": "Because the pathways are separate, the combination produces additive weight loss.", "source_ids": [ "fda-wegovy-label", "cagrilintide-phase2" ] }, { "name": "Weight loss alone", "a": "STEP 1 (1,961 adults, 68 weeks): 14.9% with semaglutide 2.4 mg versus 2.4% on placebo.", "b": "Phase 2 (706 adults, 26 weeks): 6.0% to 10.8% across 0.3 to 4.5 mg versus 3.0% on placebo; 4.5 mg beat liraglutide 3.0 mg (10.8% versus 9.0%).", "note": "Different durations and populations; REDEFINE 1 included semaglutide only and cagrilintide only arms (302 people each) as secondary comparators.", "source_ids": [ "step-1", "cagrilintide-phase2", "redefine-1" ] }, { "name": "Combination evidence", "a": "Semaglutide 2.4 mg alone lost 11.9% in REDEFINE 5 (331 adults in Japan and Taiwan, 68 weeks).", "b": "Adding cagrilintide 2.4 mg raised loss to 18.4% in REDEFINE 5, and to 20.4% versus 3.0% placebo in REDEFINE 1 (3,417 adults).", "source_ids": [ "redefine-5", "redefine-1" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT (17,604 adults): hazard ratio 0.80 for major adverse cardiovascular events in obesity with cardiovascular disease.", "b": "No cardiovascular outcomes data reported.", "source_ids": [ "select", "cagrilintide-phase2" ] }, { "name": "Regulatory status", "a": "FDA approved (Ozempic, Rybelsus, Wegovy). Compounding allowance ended after the shortage resolved in February 2025.", "b": "Not FDA approved alone or in combination. Not a component of an approved drug and not on the 503A bulks list, so it cannot lawfully be compounded.", "source_ids": [ "fda-wegovy-label", "fda-glp1-compounding", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited at all times under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Side effects", "a": "Nausea 44%, diarrhea 32%, vomiting 24%, constipation 24% in STEP 1; thyroid C-cell boxed warning.", "b": "Nausea 20% to 47% across doses versus 18% placebo in phase 2; with semaglutide, gastrointestinal events in 79.6% versus 39.9% on placebo in REDEFINE 1.", "source_ids": [ "step-1", "cagrilintide-phase2", "redefine-1" ] }, { "name": "Access and cost", "a": "Prescription at a retail pharmacy; Wegovy list about 1,349 USD per month, manufacturer cash pricing roughly 349 to 499 USD.", "b": "No lawful US access outside a registered clinical trial; products sold online as research chemicals are not lawful for human use.", "source_ids": [ "novocare", "fda-503a-bulks" ] } ], "head_to_head_studies": [ { "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 with overweight or obesity in Japan and Taiwan", "outcome": "Weight change minus 18.4% with cagrilintide plus semaglutide versus minus 11.9% with semaglutide alone (difference minus 6.5 percentage points)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/42009015/" } ], "faqs": [ { "q": "Is cagrilintide better than semaglutide for weight loss?", "a": "Not on its own. Cagrilintide alone produced 6.0% to 10.8% weight loss over 26 weeks in its phase 2 trial, while semaglutide 2.4 mg produced 14.9% over 68 weeks in STEP 1. Its value is as an add-on: combined with semaglutide it produced 20.4% weight loss in REDEFINE 1.", "source_ids": [ "cagrilintide-phase2", "step-1", "redefine-1" ] }, { "q": "What is CagriSema?", "a": "CagriSema is the investigational once weekly combination of cagrilintide 2.4 mg and semaglutide 2.4 mg. In REDEFINE 5 it produced 18.4% weight loss versus 11.9% for semaglutide alone at 68 weeks. It is not FDA approved as of the verification date.", "source_ids": [ "redefine-5", "redefine-1" ] }, { "q": "Can I get cagrilintide from a compounding pharmacy?", "a": "No. Cagrilintide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, so pharmacies cannot lawfully compound it. The only lawful access is a registered clinical trial.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Are athletes allowed to use either?", "a": "Semaglutide is not on the WADA Prohibited List. Cagrilintide is prohibited at all times under section S0 because it is not approved for human therapeutic use.", "source_ids": [ "wada-list" ] }, { "q": "Do they have the same side effects?", "a": "Both mainly cause gastrointestinal effects such as nausea, and adding cagrilintide to semaglutide increases them: gastrointestinal events affected 79.6% of people on the combination versus 39.9% on placebo in REDEFINE 1. Semaglutide also carries a thyroid C-cell tumor boxed warning.", "source_ids": [ "redefine-1", "cagrilintide-phase2", "fda-wegovy-label" ] } ], "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": "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, including section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "novocare", "type": "other", "title": "Manufacturer direct-to-patient pharmacy page with semaglutide self-pay prices, accessed 2026-09-22", "url": "https://www.novocare.com/" } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "CagriSema vs semaglutide: cagrilintide trial results", "description": "Cagrilintide vs semaglutide, and what CagriSema adds: REDEFINE trial weight loss, how amylin differs from GLP-1, side effects, and regulatory status.", "h1": "Cagrilintide vs semaglutide (and CagriSema)" } }, { "slug": "semaglutide-vs-dulaglutide", "a": "semaglutide", "b": "dulaglutide", "title": "Semaglutide vs dulaglutide", "summary": "Semaglutide (Ozempic) beat dulaglutide (Trulicity) directly in SUSTAIN 7: at matched dose tiers it lowered HbA1c by 1.5 and 1.8 points versus 1.1 and 1.4 for dulaglutide, and cut weight by 4.6 and 6.5 kg versus 2.3 and 3.0 kg over 40 weeks. Semaglutide also has an obesity indication and cardiovascular benefit in people without diabetes, while dulaglutide is diabetes only. Dulaglutide's strengths are the longest cardiovascular follow-up of any GLP-1 trial (5.4 years in REWIND) and a pediatric indication.", "verdict": { "winner": "a", "rationale": "Semaglutide wins on direct evidence (SUSTAIN 7), on breadth of label (obesity, cardiovascular risk in obesity, MASH, kidney disease, plus an oral form), and on weight loss. Dulaglutide remains a sound diabetes-only choice with a large, long cardiovascular outcomes trial, a single-use pen many patients find simple, and approval in children 10 and older, so coverage and indication usually decide in practice. Both are FDA approved and neither is available as a routine compounded product.", "source_ids": [ "sustain-7", "rewind", "select", "fda-wegovy-label", "fda-trulicity-label" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "SUSTAIN 7: HbA1c down 1.5 points (0.5 mg) and 1.8 points (1.0 mg); weight down 4.6 kg and 6.5 kg at 40 weeks.", "b": "SUSTAIN 7: HbA1c down 1.1 points (0.75 mg) and 1.4 points (1.5 mg); weight down 2.3 kg and 3.0 kg at 40 weeks.", "note": "SUSTAIN 7 randomized 1,201 adults with type 2 diabetes on metformin. Dulaglutide's later 3.0 and 4.5 mg doses (AWARD-11) were not part of this trial.", "source_ids": [ "sustain-7", "award-11" ] }, { "name": "Mechanism", "a": "Acylated GLP-1 analog that binds albumin; half life about one week.", "b": "Two GLP-1 analog chains fused to an IgG4 Fc fragment; half life about 5 days; a much larger molecule with the same receptor target.", "source_ids": [ "fda-wegovy-label", "fda-trulicity-label" ] }, { "name": "FDA labeled indications", "a": "Ozempic: type 2 diabetes, cardiovascular risk reduction, chronic kidney disease in type 2 diabetes. Wegovy: chronic weight management, cardiovascular risk reduction in obesity, MASH. Rybelsus: oral, type 2 diabetes.", "b": "Trulicity: type 2 diabetes in adults and children 10 and older, and reduction of major adverse cardiovascular events in type 2 diabetes. No weight management indication.", "source_ids": [ "fda-wegovy-label", "fda-trulicity-label" ] }, { "name": "Cardiovascular outcomes", "a": "SUSTAIN-6: hazard ratio 0.74 in type 2 diabetes (3,297 adults, median 2.1 years). SELECT: hazard ratio 0.80 in obesity without diabetes (17,604 adults).", "b": "REWIND: hazard ratio 0.88 in 9,901 adults with type 2 diabetes over a median 5.4 years, most without prior cardiovascular disease. No trial in people without diabetes.", "source_ids": [ "sustain-6", "select", "rewind" ] }, { "name": "Weight loss", "a": "14.9% vs 2.4% placebo at 68 weeks with 2.4 mg in STEP 1.", "b": "Roughly 3 to 5 kg in type 2 diabetes trials; the 4.5 mg dose lost more than the 1.5 mg dose in AWARD-11. No dedicated obesity trial.", "source_ids": [ "step-1", "award-11" ] }, { "name": "Route and dosing", "a": "Subcutaneous injection once weekly (Ozempic 0.25 mg escalating to 0.5, 1, or 2 mg; Wegovy to 2.4 mg) or oral tablet once daily (Rybelsus).", "b": "Subcutaneous injection once weekly from a single-use pen: 0.75 mg, then 1.5, 3.0, and 4.5 mg at 4-week minimum steps. No oral form.", "source_ids": [ "fda-wegovy-label", "fda-trulicity-label" ] }, { "name": "Common side effects", "a": "Nausea, diarrhea, vomiting, constipation, highest during escalation; boxed thyroid C-cell warning.", "b": "Nausea, diarrhea, vomiting, abdominal pain, decreased appetite, dose dependent and fading with continued use; gastrointestinal events were the main reason for stopping in REWIND; boxed thyroid C-cell warning.", "source_ids": [ "fda-wegovy-label", "fda-trulicity-label", "rewind" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (2017, 2019, 2021). Shortage-based compounding ended in spring 2025; no generic.", "b": "FDA approved (Trulicity 2014). 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. Not in a bulk form suitable for compounding; no generic.", "source_ids": [ "fda-glp1-compounding", "fda-trulicity-label", "fda-glp1-shortage-updates", "fda-drug-shortages-dulaglutide" ] }, { "name": "Typical cost", "a": "Ozempic list price about 998 USD per month; Wegovy about 1,349 USD; 0 to 25 USD with commercial coverage and a savings card.", "b": "Trulicity list price 1,006.93 USD per month (from 389 USD self-pay through the manufacturer pharmacy) at any strength; often 25 USD with commercial coverage and a savings card; Medicare Part D covers it for diabetes.", "source_ids": [ "fda-wegovy-label", "fda-trulicity-label", "lilly-pricing-trulicity", "lillydirect-trulicity" ] } ], "head_to_head_studies": [ { "pmid": "29397376", "title": "Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7)", "year": 2018, "design": "Phase 3b randomized, open-label, parallel-group trial, 40 weeks", "n": 1201, "population": "Adults with type 2 diabetes inadequately controlled on metformin", "outcome": "HbA1c reduction 1.5 and 1.8 points with semaglutide 0.5 and 1.0 mg vs 1.1 and 1.4 with dulaglutide 0.75 and 1.5 mg; weight loss 4.6 and 6.5 kg vs 2.3 and 3.0 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/29397376/" } ], "faqs": [ { "q": "Ozempic vs Trulicity: which lowers blood sugar more?", "a": "Semaglutide, in the direct trial. SUSTAIN 7 compared them dose tier for dose tier in 1,201 adults with type 2 diabetes and found semaglutide lowered HbA1c by 1.5 and 1.8 points versus 1.1 and 1.4 for dulaglutide at 40 weeks. Dulaglutide's higher 3.0 and 4.5 mg doses were approved later and were not in that trial.", "source_ids": [ "sustain-7", "award-11" ] }, { "q": "Can Trulicity be used for weight loss?", "a": "It is not approved for that. Dulaglutide causes modest weight loss in diabetes trials, roughly 3 to 5 kg, while semaglutide 2.4 mg (Wegovy) is approved for chronic weight management with about 15% weight loss in STEP 1.", "source_ids": [ "award-11", "step-1", "fda-wegovy-label" ] }, { "q": "Which has better heart data?", "a": "Both reduce cardiovascular events in type 2 diabetes. Dulaglutide's REWIND trial is the longest (median 5.4 years) and included mostly people without prior cardiovascular disease. Semaglutide has SUSTAIN-6 in diabetes plus SELECT in obesity without diabetes, and only semaglutide carries a cardiovascular indication for people without diabetes.", "source_ids": [ "rewind", "sustain-6", "select", "fda-wegovy-label" ] }, { "q": "Is Trulicity easier to use than Ozempic?", "a": "Its single-use pen requires no dose dialing and can be injected at any time of day, which some patients prefer. Semaglutide's advantages are an oral option (Rybelsus) and a wider dose range. Both are once weekly injections.", "source_ids": [ "fda-trulicity-label", "fda-wegovy-label" ] }, { "q": "Can children use either?", "a": "Dulaglutide is approved for type 2 diabetes in children 10 and older. Semaglutide as Wegovy is approved for weight management in adolescents 12 and older; Ozempic is not labeled for children.", "source_ids": [ "fda-trulicity-label", "fda-wegovy-label" ] } ], "sources": [ { "id": "sustain-7", "type": "pubmed", "title": "Pratley RE et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29397376/", "pmid": "29397376", "year": 2018 }, { "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": "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy", "year": 2025 }, { "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": "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": "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "Ozempic vs Trulicity (semaglutide vs dulaglutide)", "description": "Ozempic vs Trulicity: the SUSTAIN 7 head-to-head HbA1c and weight results, heart outcome trials, label doses, side effects, and cost, with sources.", "h1": "Ozempic vs Trulicity (semaglutide vs dulaglutide)" } }, { "slug": "semaglutide-vs-exenatide", "a": "semaglutide", "b": "exenatide", "title": "Semaglutide vs exenatide", "summary": "Semaglutide beat exenatide directly in SUSTAIN 3: once weekly semaglutide 1 mg lowered HbA1c by 1.5 points versus 0.9 for once weekly exenatide 2 mg and cut weight by 5.6 kg versus 1.9 kg over 56 weeks. Semaglutide also has proven cardiovascular benefit (SUSTAIN-6 and SELECT) and an obesity indication, while exenatide's cardiovascular trial (EXSCEL) was neutral and it is approved for type 2 diabetes only. Exenatide, the first drug in the class, is now mainly a legacy option.", "verdict": { "winner": "a", "rationale": "Semaglutide wins on direct randomized evidence (SUSTAIN 3), on cardiovascular outcomes (SUSTAIN-6 hazard ratio 0.74 and SELECT hazard ratio 0.80 versus EXSCEL hazard ratio 0.91, not superior to placebo), and on label breadth, since it is also approved for weight management. Both are FDA approved and both carry the human_rct evidence grade, so the difference is effect size and outcomes, not legitimacy. Exenatide mainly makes sense when a formulary or prior response favors it.", "source_ids": [ "sustain-3", "sustain-6", "select", "exscel", "fda-wegovy-label", "fda-bydureon-label" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "SUSTAIN 3 (813 adults with type 2 diabetes, 56 weeks): semaglutide 1 mg weekly lowered HbA1c by 1.5 points and weight by 5.6 kg; 67% reached HbA1c below 7%.", "b": "Exenatide extended release 2 mg weekly lowered HbA1c by 0.9 points and weight by 1.9 kg; 40% reached HbA1c below 7%.", "note": "Open label randomized trial; estimated treatment difference minus 0.62 HbA1c points and minus 3.78 kg in favor of semaglutide.", "source_ids": [ "sustain-3" ] }, { "name": "Molecule and mechanism", "a": "Acylated analog of human GLP-1 that binds albumin, half life about one week.", "b": "Synthetic exendin-4 from Gila monster saliva, about 53% identical to human GLP-1; the immediate release form has a half life of about 2.4 hours and the weekly form uses microspheres.", "note": "Both activate the same GLP-1 receptor; the difference is potency and duration of exposure.", "source_ids": [ "fda-wegovy-label", "fda-bydureon-label", "fda-byetta-label" ] }, { "name": "Cardiovascular outcomes", "a": "SUSTAIN-6 (3,297 adults with type 2 diabetes): hazard ratio 0.74 for major adverse cardiovascular events. SELECT (17,604 adults with obesity and cardiovascular disease, no diabetes): hazard ratio 0.80.", "b": "EXSCEL (14,752 adults with type 2 diabetes): 11.4% versus 12.2% major adverse cardiovascular events, hazard ratio 0.91 (95% CI 0.83 to 1.00); noninferior but not superior to placebo.", "source_ids": [ "sustain-6", "select", "exscel" ] }, { "name": "FDA labeled indications", "a": "Ozempic and Rybelsus for type 2 diabetes (Ozempic also for cardiovascular and kidney risk reduction in type 2 diabetes); Wegovy for chronic weight management, cardiovascular risk reduction in obesity, and MASH.", "b": "Byetta and Bydureon BCise for type 2 diabetes only; Bydureon BCise is also labeled for children 10 and older. No weight management indication.", "source_ids": [ "fda-wegovy-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection once weekly, or an oral tablet once daily (Rybelsus).", "b": "Subcutaneous injection twice daily before meals (Byetta, 5 then 10 ug) or once weekly (Bydureon BCise, 2 mg).", "source_ids": [ "fda-wegovy-label", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Side effects that differ", "a": "More gastrointestinal adverse events in SUSTAIN 3 (41.8%) but very few injection site reactions (1.2%).", "b": "Fewer gastrointestinal events in SUSTAIN 3 (33.3%) but far more injection site reactions (22.0%), including microsphere nodules; anti-exenatide antibodies develop in a substantial minority.", "note": "Both carry nausea, vomiting, and diarrhea during escalation, and both weekly forms carry the thyroid C-cell tumor boxed warning.", "source_ids": [ "sustain-3", "fda-bydureon-label", "fda-wegovy-label" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (2017 to 2021 products). Shortage ended February 21, 2025; routine compounding had to stop by April 22 (503A) and May 22, 2025 (503B).", "b": "FDA approved (Byetta 2005, Bydureon 2012, Bydureon BCise 2017). Never in shortage; compounding limited to documented patient specific need.", "source_ids": [ "fda-glp1-compounding", "fda-byetta-label", "fda-bydureon-label" ] }, { "name": "Typical cost", "a": "Ozempic list about 998 USD and Wegovy about 1,349 USD per month; manufacturer cash pricing for Wegovy roughly 349 to 499 USD per month.", "b": "Byetta and Bydureon BCise list roughly 800 to 1,000 USD per month; often 25 to 100 USD with commercial coverage. No generic.", "note": "Prices at the verification date change often; see the cost pages.", "source_ids": [ "novocare", "fda-bydureon-label" ] } ], "head_to_head_studies": [ { "pmid": "29246950", "title": "Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial", "year": 2018, "design": "Randomized, open label, active comparator trial, 56 weeks", "n": 813, "population": "Adults with type 2 diabetes on 1 to 2 oral glucose lowering drugs", "outcome": "HbA1c minus 1.5 versus minus 0.9 points and weight minus 5.6 versus minus 1.9 kg with semaglutide 1 mg versus exenatide ER 2 mg; injection site reactions 1.2% versus 22.0%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/29246950/" } ], "faqs": [ { "q": "Is semaglutide stronger than exenatide?", "a": "Yes, on the direct evidence. In SUSTAIN 3, semaglutide 1 mg weekly lowered HbA1c by 1.5 points versus 0.9 for exenatide extended release 2 mg, and weight by 5.6 kg versus 1.9 kg over 56 weeks.", "source_ids": [ "sustain-3" ] }, { "q": "Do both reduce heart attacks and strokes?", "a": "Semaglutide does: SUSTAIN-6 and SELECT both showed fewer major adverse cardiovascular events than placebo. Exenatide's EXSCEL trial showed it was safe for the heart but did not significantly reduce events (hazard ratio 0.91, 95% CI 0.83 to 1.00).", "source_ids": [ "sustain-6", "select", "exscel" ] }, { "q": "Can exenatide be used for weight loss?", "a": "Not on label. Exenatide is approved only for type 2 diabetes, where it produces about 2 to 4 kg of weight loss. Semaglutide 2.4 mg (Wegovy) is approved for chronic weight management.", "source_ids": [ "fda-byetta-label", "fda-bydureon-label", "fda-wegovy-label" ] }, { "q": "Why would anyone still use exenatide?", "a": "Mainly formulary coverage, prior good response, or a preference for the twice daily Byetta pen that acts mostly on post meal glucose. It remains an FDA approved option with long safety follow-up, including the 14,752 person EXSCEL trial.", "source_ids": [ "fda-byetta-label", "exscel" ] }, { "q": "Are injection site reactions different?", "a": "Yes. In SUSTAIN 3, injection site reactions occurred in 22.0% of people on extended release exenatide versus 1.2% on semaglutide, largely because of the microsphere formulation, while gastrointestinal events were somewhat more common with semaglutide.", "source_ids": [ "sustain-3" ] } ], "sources": [ { "id": "sustain-3", "type": "pubmed", "title": "Ahmann AJ et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3). Diabetes Care 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29246950/", "pmid": "29246950", "year": 2018 }, { "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": "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-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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" }, { "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" }, { "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" }, { "id": "novocare", "type": "other", "title": "Manufacturer direct-to-patient pharmacy page with semaglutide self-pay prices, accessed 2026-09-22", "url": "https://www.novocare.com/" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-liraglutide", "a": "semaglutide", "b": "liraglutide", "title": "Semaglutide vs liraglutide", "summary": "Semaglutide (Wegovy, Ozempic) produces roughly twice the weight loss of liraglutide (Saxenda, Victoza) in the only direct obesity trial: 15.8% versus 6.4% of body weight at 68 weeks in STEP 8, with one injection a week instead of one a day. Liraglutide's case is cost and track record: it has been FDA approved since 2010, has generic versions since December 2024, and has its own cardiovascular outcomes trial (LEADER). Both are FDA approved GLP-1 receptor agonists with the same gastrointestinal side effect profile and the same thyroid C-cell boxed warning.", "verdict": { "winner": "a", "rationale": "Semaglutide wins on head-to-head evidence (STEP 8), on convenience (weekly versus daily), and on the breadth of its label, which includes cardiovascular risk reduction in obesity without diabetes (SELECT) and an oral form. Liraglutide remains the better choice when price is the deciding factor, since generic liraglutide pens are on the market and no generic semaglutide exists, or when a provider wants a daily drug that can be stopped quickly. Both are lawful prescription products. Routine compounding of semaglutide ended in 2025, while liraglutide injection remains on FDA's drug shortage list as of September 2026, so ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "source_ids": [ "step-8", "select", "leader", "fda-first-generics", "fda-glp1-compounding", "fda-drug-shortages-liraglutide" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Lost 15.8% of body weight at 68 weeks with 2.4 mg weekly in STEP 8.", "b": "Lost 6.4% of body weight at 68 weeks with 3.0 mg daily in STEP 8.", "note": "STEP 8 randomized 338 adults with overweight or obesity and no diabetes. The 9.4 percentage point difference favoring semaglutide is the largest gap between two approved GLP-1 agonists in a direct trial.", "source_ids": [ "step-8" ] }, { "name": "Placebo-controlled weight loss", "a": "14.9% vs 2.4% for placebo at 68 weeks in STEP 1 (1,961 adults).", "b": "8.4 kg vs 2.8 kg for placebo at 56 weeks in SCALE Obesity and Prediabetes (3,731 adults), roughly 8% of body weight; 6.0% vs 2.0% in SCALE Diabetes.", "note": "Cross-trial comparisons are less reliable than STEP 8, but they point the same way.", "source_ids": [ "step-1", "scale-obesity", "scale-diabetes" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT: hazard ratio 0.80 for major adverse cardiovascular events in 17,604 adults with obesity and cardiovascular disease without diabetes. SUSTAIN-6: hazard ratio 0.74 in type 2 diabetes.", "b": "LEADER: hazard ratio 0.87 for major adverse cardiovascular events in 9,340 adults with type 2 diabetes over a median 3.8 years, with lower cardiovascular death (hazard ratio 0.78). No cardiovascular outcomes trial in obesity without diabetes.", "source_ids": [ "select", "sustain-6", "leader" ] }, { "name": "FDA labeled indications", "a": "Wegovy: chronic weight management (adults and adolescents 12 and older), cardiovascular risk reduction in established cardiovascular disease with obesity or overweight, and noncirrhotic MASH. Ozempic: type 2 diabetes, cardiovascular risk reduction, and chronic kidney disease in type 2 diabetes. Rybelsus: oral, type 2 diabetes.", "b": "Saxenda: chronic weight management in adults and adolescents 12 and older. Victoza: type 2 diabetes (adults and children 10 and older) and cardiovascular risk reduction in type 2 diabetes with established cardiovascular disease.", "source_ids": [ "fda-wegovy-label", "fda-saxenda-label", "fda-victoza-label" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection once weekly; oral tablet once daily available as Rybelsus.", "b": "Subcutaneous injection once daily from a prefilled pen; no oral form.", "note": "Liraglutide's half life of about 13 hours versus semaglutide's roughly one week explains the difference.", "source_ids": [ "fda-wegovy-label", "fda-saxenda-label" ] }, { "name": "Label dose escalation", "a": "Wegovy: 0.25 mg weekly for 4 weeks, then 0.5, 1, 1.7, and 2.4 mg at 4-week steps.", "b": "Saxenda: 0.6 mg daily, increased by 0.6 mg each week to 3.0 mg daily. Victoza: 0.6 mg for one week, then 1.2 mg, optional 1.8 mg.", "source_ids": [ "fda-wegovy-label", "fda-saxenda-label" ] }, { "name": "Common side effects", "a": "Nausea 44%, diarrhea 32%, vomiting 24%, constipation 24% in STEP 1 (versus 16%, 16%, 6%, and 11% on placebo).", "b": "Nausea, diarrhea, constipation, and vomiting, mostly mild to moderate; heart rate rises about 2 to 3 beats per minute; serious adverse events 6.2% vs 5.0% placebo in SCALE.", "note": "Both labels carry the thyroid C-cell boxed warning and contraindicate use with a personal or family history of medullary thyroid carcinoma or MEN 2. In STEP 8 the kinds of gastrointestinal events were similar between the two drugs.", "source_ids": [ "step-1", "scale-obesity", "step-8", "fda-wegovy-label", "fda-saxenda-label" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021). Shortage-based compounding ended in spring 2025; no generic.", "b": "FDA approved (Victoza 2010, Saxenda 2014). First generic liraglutide approved December 2024, with generics referencing Saxenda following in 2025. 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, and 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.", "source_ids": [ "fda-glp1-compounding", "fda-first-generics", "fda-saxenda-label", "fda-glp1-shortage-updates", "fr-2026-08552", "fda-drug-shortages-liraglutide" ] }, { "name": "Typical cost", "a": "Wegovy list price about 1,349 USD per month; manufacturer cash pricing roughly 349 to 499 USD per month; 0 to 25 USD with commercial coverage and a savings card.", "b": "Saxenda list price about 1,349 USD per month, but generic liraglutide pens at the diabetes strength run roughly 200 to 500 USD cash; often 25 to 100 USD with commercial coverage.", "note": "Prices at the verification date change often; see the cost pages.", "source_ids": [ "fda-wegovy-label", "fda-first-generics", "fda-saxenda-label" ] } ], "head_to_head_studies": [ { "pmid": "35015037", "title": "Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes (STEP 8)", "year": 2022, "design": "Phase 3b randomized, open-label, placebo-controlled trial, 68 weeks", "n": 338, "population": "Adults with BMI 30 or higher, or 27 or higher with at least one weight-related comorbidity, without diabetes", "outcome": "Mean weight change 15.8% with semaglutide 2.4 mg weekly vs 6.4% with liraglutide 3.0 mg daily (difference 9.4 percentage points)", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/35015037/" } ], "faqs": [ { "q": "Wegovy vs Saxenda: which causes more weight loss?", "a": "Semaglutide, by a wide margin. In STEP 8, the direct comparison in 338 adults without diabetes, semaglutide 2.4 mg weekly produced 15.8% weight loss at 68 weeks versus 6.4% with liraglutide 3.0 mg daily. The separate placebo-controlled trials agree: about 15% in STEP 1 for semaglutide versus about 8% in SCALE for liraglutide.", "source_ids": [ "step-8", "step-1", "scale-obesity" ] }, { "q": "Is Saxenda or generic liraglutide cheaper than Wegovy?", "a": "Usually, because liraglutide is generic and semaglutide is not. Generic liraglutide pens at the diabetes strength have brought cash prices to roughly 200 to 500 USD per month, versus about 1,349 USD list for Wegovy or roughly 349 to 499 USD through the manufacturer cash program. With commercial coverage and savings cards both can be inexpensive, so check coverage for your indication first.", "source_ids": [ "fda-first-generics", "fda-saxenda-label", "fda-wegovy-label" ] }, { "q": "Do Ozempic and Victoza both protect the heart?", "a": "Both have positive cardiovascular outcomes trials, but in different populations. Liraglutide's LEADER trial showed a 13% relative reduction in major adverse cardiovascular events in people with type 2 diabetes. Semaglutide has that too (SUSTAIN-6) plus SELECT, which showed a 20% relative reduction in people with obesity and cardiovascular disease but no diabetes, and Wegovy carries an indication for that use. Saxenda does not.", "source_ids": [ "leader", "sustain-6", "select", "fda-wegovy-label" ] }, { "q": "Are the side effects different?", "a": "Not in kind. Both cause nausea, diarrhea, vomiting, and constipation that peak during dose escalation, and both labels carry the thyroid C-cell boxed warning. Liraglutide's daily dosing means side effects can be stopped faster, while semaglutide's weekly half life means an adverse effect persists for days after a dose.", "source_ids": [ "step-1", "scale-obesity", "fda-wegovy-label", "fda-saxenda-label" ] }, { "q": "Can I switch from Saxenda to Wegovy?", "a": "Switching is common in practice, but neither label includes a switching schedule and STEP 8 did not study it. The Wegovy label starts at 0.25 mg weekly regardless of prior GLP-1 exposure. Discuss timing with the prescriber rather than following an online protocol.", "source_ids": [ "fda-wegovy-label", "step-8" ] }, { "q": "Can either be compounded?", "a": "Semaglutide, not routinely: FDA ended the shortage-based allowance for compounded semaglutide in spring 2025. Liraglutide is different: 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. 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. Brand and generic liraglutide are also marketed, and on April 30, 2026 FDA proposed not to include liraglutide on the 503B bulks list. Ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "source_ids": [ "fda-glp1-compounding", "fda-first-generics", "fda-glp1-shortage-updates", "fr-2026-08552", "fda-drug-shortages-liraglutide" ] } ], "sources": [ { "id": "step-8", "type": "pubmed", "title": "Rubino DM et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35015037/", "pmid": "35015037", "year": 2022 }, { "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": "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": "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": "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy", "year": 2025 }, { "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": "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "Wegovy vs Saxenda (semaglutide vs liraglutide)", "description": "Wegovy vs Saxenda: 15.8% versus 6.4% weight loss in the STEP 8 head-to-head trial, plus heart data, side effects, label doses, generics, and cost.", "h1": "Wegovy vs Saxenda and Ozempic vs Victoza (semaglutide vs liraglutide)" } }, { "slug": "semaglutide-vs-mazdutide", "a": "semaglutide", "b": "mazdutide", "title": "Semaglutide vs mazdutide", "summary": "In the only head-to-head trial, DREAMS-3 in 349 Chinese adults with type 2 diabetes and obesity, mazdutide 6 mg beat semaglutide 1 mg: 48.0% versus 21.0% reached both an HbA1c under 7% and at least 10% weight loss at 32 weeks, with 10.3% versus 6.0% weight loss, according to the manufacturer's topline release. Semaglutide is FDA approved with proven cardiovascular benefit (SELECT, SUSTAIN-6), while mazdutide is approved only in China and has no lawful United States access path.", "verdict": { "winner": "depends", "rationale": "On the trial evidence alone, mazdutide produced more weight loss and slightly more HbA1c lowering than semaglutide 1 mg in DREAMS-3, although that result is so far a manufacturer topline announcement and the semaglutide dose was the diabetes dose, not the 2.4 mg obesity dose. For anyone in the United States the practical answer is semaglutide: it is FDA approved, has completed cardiovascular outcomes trials, and can be prescribed, whereas mazdutide is approved only by China's regulator and cannot lawfully be compounded or sold in the United States.", "source_ids": [ "dreams-3-topline", "dreams-3-design", "select", "sustain-6", "mazdutide-china-obesity-approval", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Semaglutide 1 mg weekly: 21.0% reached HbA1c under 7% plus at least 10% weight loss; HbA1c fell 1.84 points and weight 6.0% at 32 weeks in DREAMS-3.", "b": "Mazdutide 6 mg weekly: 48.0% reached the composite goal; HbA1c fell 2.03 points and weight 10.3% at 32 weeks in DREAMS-3.", "note": "DREAMS-3 was open label and enrolled 349 Chinese adults with type 2 diabetes of 10 years or less and a BMI of 28 or higher. Results come from the manufacturer's October 2025 release; the design paper is indexed, the full results were not found in PubMed on the verification date.", "source_ids": [ "dreams-3-topline", "dreams-3-design" ] }, { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist.", "b": "Dual GLP-1 and glucagon receptor agonist (oxyntomodulin analog); glucagon receptor activity adds energy expenditure and liver fat oxidation.", "source_ids": [ "fda-wegovy-label", "glory-1" ] }, { "name": "Placebo-controlled weight loss", "a": "14.9% versus 2.4% on placebo at 68 weeks with 2.4 mg in STEP 1 (1,961 adults).", "b": "11.0% and 14.0% at 4 and 6 mg versus 0.3% gain on placebo at 48 weeks in GLORY-1 (610 Chinese adults); 18.1% at 16 mg versus 0.9% at 32 weeks in a US phase 2 trial (179 adults).", "note": "Different populations, doses, and durations; the direct trial above is the better guide.", "source_ids": [ "step-1", "glory-1", "mazdutide-us-phase2" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT: 20% relative reduction in major adverse cardiovascular events (hazard ratio 0.80) in 17,604 adults with obesity and cardiovascular disease; SUSTAIN-6: hazard ratio 0.74 in type 2 diabetes.", "b": "No cardiovascular outcomes trial has reported.", "source_ids": [ "select", "sustain-6", "glory-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021). The shortage-based compounding allowance ended in 2025.", "b": "Approved in China for chronic weight management (June 2025) and type 2 diabetes (September 2025). Not FDA approved, not on the 503A bulks list, and not lawfully compounded or sold in the United States.", "source_ids": [ "fda-wegovy-label", "fda-shortage-clarification", "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not named on the list. Because it is approved in China, section S0 (non-approved substances) may not apply; athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list", "mazdutide-china-obesity-approval" ] }, { "name": "Side effects", "a": "Nausea 44%, diarrhea 32%, vomiting 24%, constipation 24% at 2.4 mg in STEP 1; boxed warning for thyroid C-cell tumors.", "b": "Diarrhea 36%, decreased appetite 29%, nausea 23%, vomiting 14% in the type 2 diabetes phase 2 trial; gastrointestinal events mostly mild to moderate in DREAMS-3. No US label, so no boxed warning has been issued.", "source_ids": [ "step-1", "fda-wegovy-label", "mazdutide-t2d-phase2", "dreams-3-topline" ] }, { "name": "Route and dosing", "a": "Once weekly injection (0.25 mg escalated to 2.4 mg for weight, up to 2 mg for diabetes) or a once daily tablet.", "b": "Once weekly injection; trial maintenance doses of 4 or 6 mg (GLORY-1) and up to 16 mg in the US phase 2 trial. No approved US label.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "glory-1", "mazdutide-us-phase2" ] } ], "head_to_head_studies": [ { "pmid": "41260459", "title": "Mazdutide versus semaglutide for the treatment of type 2 diabetes and obesity: rationale, design and baseline data of the DREAMS-3 phase 3 trial", "year": 2026, "design": "Randomized, open label, active controlled phase 3 trial, 32 weeks plus 24 week extension (design and baseline paper)", "n": 349, "population": "Chinese adults with type 2 diabetes of 10 years or less and BMI 28 or higher", "outcome": "Design and baseline only; results pending publication. Topline figures are in the head-to-head evidence row, cited to the manufacturer announcement.", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/41260459/" } ], "faqs": [ { "q": "Is mazdutide stronger than semaglutide?", "a": "In DREAMS-3, the one direct trial, mazdutide 6 mg produced 10.3% weight loss versus 6.0% with semaglutide 1 mg at 32 weeks and lowered HbA1c by 2.03 versus 1.84 points, per the manufacturer's topline release. The trial used the diabetes dose of semaglutide, not the 2.4 mg obesity dose.", "source_ids": [ "dreams-3-topline", "dreams-3-design" ] }, { "q": "Can I get mazdutide in the United States?", "a": "No lawful path exists outside a registered clinical trial. Mazdutide is not FDA approved, is not on the 503A bulks list, and cannot be compounded; it is approved only in China.", "source_ids": [ "fda-503a-bulks", "mazdutide-china-obesity-approval" ] }, { "q": "Does mazdutide protect the heart like semaglutide?", "a": "Unknown. Semaglutide reduced major cardiovascular events by 20% in SELECT and 26% in SUSTAIN-6. No cardiovascular outcomes trial of mazdutide has reported.", "source_ids": [ "select", "sustain-6" ] }, { "q": "Do they have the same side effects?", "a": "Both mainly cause gastrointestinal effects. Semaglutide caused nausea in 44% in STEP 1; mazdutide caused diarrhea in 36% and nausea in 23% in its type 2 diabetes phase 2 trial. Only semaglutide has an FDA label with the thyroid C-cell boxed warning, because mazdutide has no US label.", "source_ids": [ "step-1", "mazdutide-t2d-phase2", "fda-wegovy-label" ] } ], "sources": [ { "id": "dreams-3-topline", "type": "other", "title": "Manufacturer press release: DREAMS-3 phase 3 head-to-head results of mazdutide versus semaglutide (October 26, 2025), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/innovents-mazdutide-shows-superiority-in-glycemic-control-with-weight-loss-over-semaglutide-in-a-head-to-head-phase-3-clinical-trial-dreams-3-302594633.html", "year": 2025 }, { "id": "dreams-3-design", "type": "pubmed", "title": "Luo Y et al. Mazdutide versus semaglutide for the treatment of type 2 diabetes and obesity: rationale, design and baseline data of the DREAMS-3 phase 3 trial. Contemp Clin Trials 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41260459/", "pmid": "41260459", "year": 2026 }, { "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": "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": "mazdutide-china-obesity-approval", "type": "other", "title": "Manufacturer press release: China's drug regulator (NMPA) approves mazdutide for chronic weight management (June 27, 2025), accessed 2026-09-22", "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": "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" }, { "id": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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": "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": "mazdutide-us-phase2", "type": "pubmed", "title": "Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based phase 2 randomised placebo-controlled trial. Lancet Diabetes Endocrinol 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42628555/", "pmid": "42628555", "year": 2026 }, { "id": "fda-shortage-clarification", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (shortage resolution and compounding end dates)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize" }, { "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), accessed 2026-09-22", "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 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "mazdutide-t2d-phase2", "type": "pubmed", "title": "Zhang B et al. Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. Diabetes Care 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37943529/", "pmid": "37943529", "year": 2024 }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-retatrutide", "a": "semaglutide", "b": "retatrutide", "title": "Semaglutide vs retatrutide", "summary": "Semaglutide is FDA approved, available by prescription, and backed by trials in tens of thousands of people, including a proven reduction in cardiovascular events (SELECT). Retatrutide is an investigational triple agonist whose 24.2% weight loss at 48 weeks in a 338 person phase 2 trial exceeds semaglutide's 14.9% at 68 weeks in STEP 1, but it is not approved, cannot be compounded, and is prohibited in sport. No head-to-head trial exists.", "verdict": { "winner": "a", "rationale": "Semaglutide wins because it is the only one of the two that is lawful to prescribe and the only one with outcome data beyond weight: SELECT and SUSTAIN-6 showed fewer cardiovascular events, and its label covers obesity, diabetes, cardiovascular risk, MASH, and kidney disease. Retatrutide's phase 2 weight loss is larger, but the trial was small and short, safety beyond one year is unknown, and it is a WADA section S0 substance. Revisit if phase 3 (TRIUMPH) leads to approval.", "source_ids": [ "step-1", "select", "retatrutide-phase2-obesity", "triumph-design", "fda-wegovy-label", "fda-glp1-compounding", "wada-list" ] }, "dimensions": [ { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist.", "b": "Triple GIP, GLP-1, and glucagon receptor agonist.", "source_ids": [ "fda-wegovy-label", "retatrutide-phase2-obesity" ] }, { "name": "Weight loss in the pivotal trial", "a": "14.9% vs 2.4% placebo at 68 weeks with 2.4 mg weekly in STEP 1 (1,961 adults).", "b": "24.2% vs 2.1% placebo at 48 weeks with 12 mg weekly in the phase 2 trial (338 adults); 83% lost at least 15%.", "note": "Not a direct comparison. Trial size, duration, and population differ.", "source_ids": [ "step-1", "retatrutide-phase2-obesity" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT: hazard ratio 0.80 for major adverse cardiovascular events in 17,604 adults with obesity and cardiovascular disease. SUSTAIN-6: hazard ratio 0.74 in type 2 diabetes.", "b": "No cardiovascular outcomes trial has reported. Heart rate rises more than with GLP-1 only agonists.", "source_ids": [ "select", "sustain-6", "retatrutide-phase2-obesity" ] }, { "name": "Type 2 diabetes evidence", "a": "Approved (Ozempic, Rybelsus); SUSTAIN program plus cardiovascular and kidney indications.", "b": "Phase 2 (281 adults, 36 weeks) and phase 3 TRANSCEND-T2D-1 (537 adults, 40 weeks) show HbA1c and weight reductions; no approval.", "source_ids": [ "fda-wegovy-label", "sustain-6", "retatrutide-phase2-t2d", "transcend-t2d-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021). Shortage-based compounding ended in spring 2025.", "b": "Not approved anywhere; not compoundable under 503A or 503B; lawful only inside a registered clinical trial.", "source_ids": [ "fda-wegovy-label", "fda-glp1-compounding", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited at all times under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Route and dosing", "a": "Subcutaneous injection once weekly (Wegovy 0.25 mg escalating to 2.4 mg) or oral tablet once daily (Rybelsus).", "b": "Subcutaneous injection once weekly in trials only, escalated to 1, 4, 8, or 12 mg. No approved dose.", "source_ids": [ "fda-wegovy-label", "retatrutide-phase2-obesity" ] }, { "name": "Side effects", "a": "Nausea 44%, diarrhea 32%, vomiting 24%, constipation 24% in STEP 1; boxed thyroid C-cell warning; gallbladder and pancreatitis warnings.", "b": "Dose-related gastrointestinal effects partly reduced by a lower starting dose; larger heart rate increase; skin sensitivity; no long-term safety data.", "source_ids": [ "step-1", "fda-wegovy-label", "retatrutide-phase2-obesity" ] }, { "name": "Typical cost", "a": "Wegovy list price about 1,349 USD per month; manufacturer cash pricing roughly 349 to 499 USD; 0 to 25 USD with commercial coverage and a savings card.", "b": "No lawful price; trial participants receive it free. Online listings are unapproved and unverified.", "source_ids": [ "fda-wegovy-label", "fda-glp1-compounding" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is retatrutide stronger than semaglutide for weight loss?", "a": "The trial numbers say yes: 24.2% at 48 weeks for retatrutide 12 mg versus 14.9% at 68 weeks for semaglutide 2.4 mg. But those come from a 338 person phase 2 trial and a 1,961 person phase 3 trial that were never compared directly. Phase 3 retatrutide results are needed before the gap can be stated with confidence.", "source_ids": [ "retatrutide-phase2-obesity", "step-1" ] }, { "q": "Can I be prescribed retatrutide?", "a": "No. It is investigational, not approved by FDA or any other regulator, and cannot be compounded because it is not a component of an approved drug and is not on any bulks list. Semaglutide is available by prescription as Ozempic, Wegovy, or Rybelsus.", "source_ids": [ "fda-glp1-compounding", "fda-503a-bulks", "fda-wegovy-label" ] }, { "q": "Which is safer?", "a": "Semaglutide has the safety record: an approved label, trials in tens of thousands of people, and cardiovascular outcomes trials showing benefit. Retatrutide's safety is known only from about a year of data in a few hundred people, and its glucagon activity raises heart rate more than semaglutide does.", "source_ids": [ "select", "fda-wegovy-label", "retatrutide-phase2-obesity" ] }, { "q": "Is retatrutide banned in sport?", "a": "Yes. WADA section S0 prohibits any substance with no current approval from a government health authority, which covers retatrutide at all times. Semaglutide is not prohibited.", "source_ids": [ "wada-list" ] }, { "q": "Will retatrutide replace semaglutide?", "a": "Unknown. Retatrutide's phase 3 program (TRIUMPH) covers obesity, sleep apnea, and knee osteoarthritis, and it will need FDA review before any comparison of approved products is possible. Semaglutide's advantages today are its cardiovascular, MASH, and kidney indications and its oral form.", "source_ids": [ "triumph-design", "fda-wegovy-label" ] } ], "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": "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": "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": "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-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, 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", "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", "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-setmelanotide", "a": "semaglutide", "b": "setmelanotide", "title": "Semaglutide vs setmelanotide", "summary": "Semaglutide treats common obesity and type 2 diabetes, with 14.9% weight loss in STEP 1 and a 20% cut in cardiovascular events in SELECT. Setmelanotide treats rare obesity caused by broken melanocortin signaling (POMC, PCSK1, or LEPR deficiency, Bardet-Biedl syndrome) or acquired hypothalamic obesity. They are not alternatives for the same patient; the diagnosis decides.", "verdict": { "winner": "depends", "rationale": "For common obesity, semaglutide is approved, more effective on average, has cardiovascular outcomes evidence, and comes as a weekly injection or daily tablet, while setmelanotide is not indicated. For a confirmed genetic defect in the melanocortin pathway or hypothalamic obesity, setmelanotide acts downstream of the defect and is the drug labeled for that cause. They have never been compared directly.", "source_ids": [ "step-1", "select", "fda-wegovy-label", "fda-imcivree-label", "clement-2020", "setmelanotide-ho-approval" ] }, "dimensions": [ { "name": "Who it is for", "a": "Wegovy: chronic weight management in adults and adolescents 12 and older, cardiovascular risk reduction, and MASH with fibrosis. Ozempic and Rybelsus: type 2 diabetes.", "b": "Imcivree: chronic weight management in obesity due to POMC, PCSK1, or LEPR deficiency (2020) or Bardet-Biedl syndrome (2022), extended to age 2 and older in December 2024, and acquired hypothalamic obesity in patients 4 and older (March 2026). Not indicated for common obesity.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-imcivree-label", "setmelanotide-ho-approval" ] }, { "name": "Mechanism", "a": "GLP-1 receptor agonist.", "b": "Melanocortin-4 receptor agonist acting in the hypothalamus.", "source_ids": [ "fda-wegovy-label", "fda-imcivree-label" ] }, { "name": "Weight loss evidence", "a": "14.9% versus 2.4% on placebo at 68 weeks (STEP 1, 1,961 adults).", "b": "Bardet-Biedl syndrome: 32% of patients 12 and older lost at least 10% at 52 weeks; POMC or PCSK1 deficiency: 80% lost at least 10% at one year.", "source_ids": [ "step-1", "haqq-2022", "clement-2020" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT: 20% relative reduction in major adverse cardiovascular events (hazard ratio 0.80).", "b": "No cardiovascular outcomes trial; not studied for this purpose.", "source_ids": [ "select", "fda-imcivree-label" ] }, { "name": "Side effects", "a": "Nausea 44%, diarrhea 32%, vomiting 24% in STEP 1; thyroid C-cell boxed warning; gallbladder disease.", "b": "Injection site reactions, hyperpigmentation, nausea, spontaneous erections; label warning about depression and suicidal ideation.", "source_ids": [ "step-1", "fda-wegovy-label", "fda-imcivree-label" ] }, { "name": "Route and frequency", "a": "Once weekly injection or once daily tablet.", "b": "Once daily injection.", "source_ids": [ "fda-wegovy-label", "fda-imcivree-label" ] }, { "name": "Regulatory status", "a": "FDA approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021). Shortage-based compounding ended in 2025.", "b": "FDA approved (Imcivree 2020, expanded to acquired hypothalamic obesity in March 2026). Not a compounding candidate.", "source_ids": [ "fda-wegovy-label", "fda-shortage-clarification", "fda-imcivree-label", "setmelanotide-ho-approval" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not on the WADA Prohibited List.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Should someone with a POMC or LEPR mutation take semaglutide or setmelanotide?", "a": "Setmelanotide is the drug approved for obesity caused by POMC, PCSK1, or LEPR deficiency; in phase 3, 80% of POMC deficient patients lost at least 10% of body weight. Semaglutide has not been studied specifically in these conditions, so the choice belongs to a specialist.", "source_ids": [ "fda-imcivree-label", "clement-2020" ] }, { "q": "Is setmelanotide a stronger weight loss drug than semaglutide?", "a": "Not for common obesity, where it is not indicated. Its large effects are in people whose obesity is caused by a defect in the melanocortin pathway.", "source_ids": [ "fda-imcivree-label", "clement-2020" ] }, { "q": "Does either one come as a pill?", "a": "Semaglutide does, as a once daily tablet for type 2 diabetes and for weight management. Setmelanotide is only a daily injection.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-imcivree-label" ] }, { "q": "What is acquired hypothalamic obesity and which drug is approved for it?", "a": "It is rapid weight gain after damage to the hypothalamus, for example from a tumor or its treatment. In March 2026 FDA approved setmelanotide for it in patients 4 and older; semaglutide is not labeled for it.", "source_ids": [ "setmelanotide-ho-approval", "fda-wegovy-label" ] } ], "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "id": "fda-imcivree-label", "type": "fda", "title": "FDA prescribing information for Imcivree (setmelanotide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=imcivree" }, { "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: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33137293/", "pmid": "33137293", "year": 2020 }, { "id": "setmelanotide-ho-approval", "type": "other", "title": "Trade press report: FDA approves setmelanotide for acquired hypothalamic obesity in patients 4 and older (March 19, 2026), accessed 2026-09-22", "url": "https://www.docwirenews.com/post/fda-approves-expanded-indication-for-setmelanotide-as-first-and-only-approved-therapy-for-acquired-hypothalamic-obesity", "year": 2026 }, { "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": "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": "fda-shortage-clarification", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (shortage resolution and compounding end dates)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-survodutide", "a": "semaglutide", "b": "survodutide", "title": "Semaglutide vs survodutide", "summary": "Semaglutide is the better supported and the only available choice: it is FDA approved, produced 14.9% weight loss in STEP 1, and cut cardiovascular events by 20% in SELECT. Survodutide, an investigational glucagon and GLP-1 dual agonist, lowered weight more than open-label semaglutide 1 mg at doses of 1.8 mg and above in a 16 week phase 2 diabetes trial but caused more adverse events (77.8% versus 52.0%), and its phase 3 obesity result was 12.2% to 13.0% at 76 weeks.", "verdict": { "winner": "a", "rationale": "The only direct trial was short (16 weeks) and phase 2: survodutide matched semaglutide 1 mg on HbA1c at low dose and beat it on weight at 1.8 mg and above, with more gastrointestinal adverse events. Semaglutide has phase 3 and cardiovascular outcomes evidence, an FDA label, and lawful access. Survodutide's distinctive signal is liver disease (MASH), which matters for trial choices but not for anyone seeking treatment today.", "source_ids": [ "survodutide-t2d-phase2", "step-1", "select", "synchronize-1", "survodutide-mash-phase2" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Semaglutide up to 1 mg weekly (open label): HbA1c fell 1.47 points and weight 5.3% at 16 weeks.", "b": "Survodutide 0.9 mg weekly lowered HbA1c 1.46 points, similar to semaglutide; doses of 1.8 mg weekly and above lowered weight more than semaglutide, up to 8.7% at 16 weeks.", "note": "Phase 2 trial of 413 adults with type 2 diabetes on metformin; the semaglutide arm was open label while survodutide and placebo were blinded.", "source_ids": [ "survodutide-t2d-phase2" ] }, { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist.", "b": "Dual glucagon and GLP-1 receptor agonist; glucagon activity raises energy expenditure and liver fat oxidation.", "source_ids": [ "fda-wegovy-label", "synchronize-1" ] }, { "name": "Phase 3 weight loss", "a": "14.9% versus 2.4% on placebo at 68 weeks (STEP 1, 1,961 adults, 2.4 mg).", "b": "12.2% (3.6 mg) and 13.0% (6.0 mg) versus 5.4% on placebo at 76 weeks (SYNCHRONIZE-1, 725 adults).", "note": "Separate trials with different estimands and durations; not a direct comparison.", "source_ids": [ "step-1", "synchronize-1" ] }, { "name": "Liver disease evidence", "a": "FDA granted accelerated approval of Wegovy for MASH with moderate to advanced fibrosis in 2025.", "b": "Phase 2 MASH trial (293 adults): improvement without worsening fibrosis in 47% to 62% versus 14% on placebo at 48 weeks.", "source_ids": [ "fda-wegovy-label", "survodutide-mash-phase2" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT hazard ratio 0.80 in obesity with cardiovascular disease; SUSTAIN-6 hazard ratio 0.74 in type 2 diabetes.", "b": "No outcomes trial has reported.", "source_ids": [ "select", "sustain-6", "synchronize-1" ] }, { "name": "Tolerability", "a": "Adverse events in 52.0% on semaglutide 1 mg in the direct trial.", "b": "Adverse events in 77.8% on survodutide in the direct trial, mainly gastrointestinal; gastrointestinal symptoms in 80.9% to 89.7% versus 47.9% on placebo in SYNCHRONIZE-1.", "source_ids": [ "survodutide-t2d-phase2", "synchronize-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Ozempic, Rybelsus, Wegovy). Shortage-based compounding ended in 2025.", "b": "Investigational; not approved by FDA or any other regulator, not on the 503A bulks list, and cannot lawfully be compounded.", "source_ids": [ "fda-wegovy-label", "fda-shortage-clarification", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [ { "pmid": "38095657", "title": "Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes", "year": 2024, "design": "Randomized, double blind, placebo controlled phase 2 trial with an open label semaglutide arm, 16 weeks", "n": 413, "population": "Adults with type 2 diabetes on metformin, HbA1c 7.0% to 10.0%, BMI 25 to 50", "outcome": "HbA1c change minus 1.46 points with survodutide 0.9 mg versus minus 1.47 with semaglutide 1 mg; weight change up to minus 8.7% with survodutide versus minus 5.3% with semaglutide; adverse events 77.8% versus 52.0%", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/38095657/" } ], "faqs": [ { "q": "Does survodutide cause more weight loss than semaglutide?", "a": "In a 16 week phase 2 diabetes trial, survodutide at 1.8 mg weekly and above lowered weight more than semaglutide 1 mg (up to 8.7% versus 5.3%). No trial has compared it with the 2.4 mg obesity dose of semaglutide.", "source_ids": [ "survodutide-t2d-phase2" ] }, { "q": "Is survodutide approved?", "a": "No. It is investigational, cannot lawfully be compounded in the United States, and is only available inside registered clinical trials.", "source_ids": [ "fda-503a-bulks", "synchronize-1" ] }, { "q": "Which is better for fatty liver disease?", "a": "Semaglutide is the one that is approved: FDA granted Wegovy accelerated approval for MASH with fibrosis in 2025. Survodutide has strong phase 2 liver data (MASH improvement in up to 62% versus 14% on placebo) but no approval.", "source_ids": [ "fda-wegovy-label", "survodutide-mash-phase2" ] }, { "q": "Are athletes allowed to use either one?", "a": "Semaglutide is not on the WADA Prohibited List. Survodutide is prohibited under section S0 because no regulator has approved it.", "source_ids": [ "wada-list" ] } ], "sources": [ { "id": "survodutide-t2d-phase2", "type": "pubmed", "title": "Bluher M et al. Dose-response effects on HbA1c and bodyweight reduction of survodutide compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38095657/", "pmid": "38095657", "year": 2024 }, { "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": "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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": "fda-shortage-clarification", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (shortage resolution and compounding end dates)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semaglutide-vs-tirzepatide", "a": "semaglutide", "b": "tirzepatide", "title": "Semaglutide vs tirzepatide", "summary": "Tirzepatide (Zepbound, Mounjaro) produces more weight loss than semaglutide (Wegovy, Ozempic) in the only direct obesity trial: 20.2% versus 13.7% of body weight at 72 weeks in SURMOUNT-5, and it lowered HbA1c and weight more than semaglutide 1 mg in SURPASS-2 in type 2 diabetes. Semaglutide has the broader label, including a proven reduction in major cardiovascular events in people with obesity but no diabetes (SELECT), an approval for MASH, and tablet forms. Both are FDA approved, once weekly injections with the same class of gastrointestinal side effects and the same thyroid C-cell boxed warning.", "verdict": { "winner": "depends", "rationale": "For weight loss alone, tirzepatide wins on head-to-head evidence (SURMOUNT-5 and SURPASS-2). For a patient with established cardiovascular disease and obesity but no diabetes, semaglutide is the only one of the two with a completed cardiovascular outcomes trial in that group and an FDA labeled indication to reduce major adverse cardiovascular events there. Tolerability, cost, and insurance coverage for the specific indication usually decide between them in practice.", "source_ids": [ "surmount-5", "surpass-2", "select", "fda-wegovy-label", "fda-zepbound-label" ] }, "dimensions": [ { "name": "Head-to-head evidence", "a": "Lost 13.7% of body weight at 72 weeks in SURMOUNT-5 (semaglutide 2.4 mg or maximum tolerated dose). Lowered HbA1c by 1.86 points at 40 weeks in SURPASS-2 (1 mg dose).", "b": "Lost 20.2% of body weight at 72 weeks in SURMOUNT-5 (tirzepatide 15 mg or maximum tolerated dose). Lowered HbA1c by 2.01 to 2.30 points and weight by 7.6 to 11.2 kg at 40 weeks in SURPASS-2 across 5, 10, and 15 mg doses.", "note": "SURMOUNT-5 randomized 751 adults with obesity and no diabetes. SURPASS-2 randomized 1,879 adults with type 2 diabetes on metformin and compared tirzepatide with semaglutide 1 mg, not the 2.4 mg obesity dose.", "source_ids": [ "surmount-5", "surpass-2" ] }, { "name": "Placebo-controlled weight loss", "a": "14.9% vs 2.4% for placebo at 68 weeks in STEP 1 (1,961 adults with overweight or obesity).", "b": "15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg vs 3.1% for placebo at 72 weeks in SURMOUNT-1 (2,539 adults).", "note": "Cross-trial comparisons are unreliable; the direct trial (SURMOUNT-5) is the better guide.", "source_ids": [ "step-1", "surmount-1" ] }, { "name": "Mechanism", "a": "Selective GLP-1 receptor agonist.", "b": "Dual GIP and GLP-1 receptor agonist.", "source_ids": [ "fda-wegovy-label", "fda-zepbound-label" ] }, { "name": "FDA labeled indications", "a": "Wegovy (injection and tablets): chronic weight management (the injection also from age 12), reduction of major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight, and, for the injection, noncirrhotic MASH with moderate to advanced fibrosis. Ozempic: type 2 diabetes, cardiovascular risk reduction in type 2 diabetes, and kidney outcomes in type 2 diabetes with chronic kidney disease. Rybelsus and Ozempic tablets: type 2 diabetes.", "b": "Zepbound: chronic weight management in adults and moderate to severe obstructive sleep apnea in adults with obesity. Mounjaro: type 2 diabetes in adults and children 10 and older, and reduction of major adverse cardiovascular events in adults with type 2 diabetes at high cardiovascular risk.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-zepbound-label", "fda-mounjaro-label" ] }, { "name": "Cardiovascular outcomes", "a": "SELECT: 20% relative reduction in major adverse cardiovascular events vs placebo (hazard ratio 0.80) in 17,604 adults with cardiovascular disease and overweight or obesity without diabetes. SUSTAIN-6: hazard ratio 0.74 in type 2 diabetes.", "b": "No completed cardiovascular outcomes trial in obesity without diabetes, and the Zepbound label has no cardiovascular indication. In type 2 diabetes with cardiovascular disease, SURPASS-CVOT (13,165 adults) found tirzepatide noninferior to dulaglutide (hazard ratio 0.92), and the Mounjaro label now carries a cardiovascular risk reduction indication.", "source_ids": [ "select", "sustain-6", "fda-zepbound-label", "surpass-cvot", "fda-mounjaro-label" ] }, { "name": "Common side effects", "a": "Nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue. Rates are highest during dose escalation.", "b": "Nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue. In SURPASS-2 gastrointestinal events were similar in kind to semaglutide and dose dependent.", "note": "Both labels carry a boxed warning for thyroid C-cell tumors seen in rodents and are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Both warn about pancreatitis, gallbladder disease, hypoglycemia with insulin or sulfonylureas, and delayed gastric emptying.", "source_ids": [ "fda-wegovy-label", "fda-zepbound-label", "surpass-2" ] }, { "name": "Regulatory status", "a": "FDA approved: Ozempic (2017), Rybelsus (2019), Wegovy (2021). Compounding allowance ended after the shortage was resolved on February 21, 2025 (503A grace period ended April 22, 2025).", "b": "FDA approved: Mounjaro (May 2022), Zepbound (November 2023). Compounding allowance ended after the shortage was resolved on December 19, 2024 (503A grace period ended February 18, 2025).", "source_ids": [ "fda-glp1-compounding", "fda-wegovy-label", "fda-zepbound-label" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Not on the WADA Prohibited List.", "note": "Neither drug is prohibited in sport, but athletes should confirm any co-prescribed agent against the current list.", "source_ids": [ "wada-list" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection once weekly (Wegovy or Ozempic pen). Once daily tablets: Wegovy tablets for weight management, and Ozempic tablets and Rybelsus for type 2 diabetes.", "b": "Subcutaneous injection once weekly (Zepbound or Mounjaro single-dose pen, single-dose vial, multi-dose vial, or KwikPen). No oral form.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-zepbound-label", "fda-mounjaro-label" ] }, { "name": "Label dose escalation", "a": "Wegovy injection: 0.25 mg weekly for 4 weeks, then 0.5, 1, and 1.7 mg at 4-week steps; 2.4 mg (or 1.7 mg) maintenance, with an optional increase to a 7.2 mg maximum for weight reduction in adults. Ozempic: 0.25 mg, then 0.5 mg, with optional 1 mg and 2 mg steps.", "b": "Zepbound and Mounjaro: 2.5 mg weekly for 4 weeks, then 5 mg, with optional 2.5 mg increases after at least 4 weeks up to a 15 mg maximum. Zepbound maintenance is 5, 10, or 15 mg for weight and 10 or 15 mg for sleep apnea.", "source_ids": [ "fda-wegovy-label", "fda-ozempic-label", "fda-zepbound-label", "fda-mounjaro-label" ] }, { "name": "Typical cost", "a": "Wegovy list price 1,349.02 USD per month and Ozempic 1,027.51 USD. Manufacturer self-pay: Wegovy tablets from 149 USD per month and the Wegovy pen 349 USD (399 USD at 7.2 mg); as little as 25 USD with commercial coverage and the savings offer.", "b": "Zepbound list price up to 1,086.37 USD per fill and Mounjaro 1,112.16 USD. Manufacturer self-pay Zepbound vials or KwikPen: 299 USD at 2.5 mg up to 699 USD at 10 mg and above; as little as 25 USD with commercial coverage and a savings card.", "note": "Prices checked 2026-09-22 on manufacturer pages and change often; see the cost pages for each drug and channel.", "source_ids": [ "novocare", "lillydirect" ] } ], "head_to_head_studies": [ { "pmid": "40353578", "title": "Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5)", "year": 2025, "design": "Phase 3b open-label randomized controlled trial, 72 weeks", "n": 751, "population": "Adults with obesity, or overweight plus at least one weight-related complication, without type 2 diabetes", "outcome": "Mean weight change 20.2% with tirzepatide vs 13.7% with semaglutide at 72 weeks", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/40353578/" }, { "pmid": "34170647", "title": "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2)", "year": 2021, "design": "Phase 3 open-label randomized controlled trial, 40 weeks", "n": 1879, "population": "Adults with type 2 diabetes inadequately controlled on metformin", "outcome": "HbA1c reduction 2.01, 2.24, and 2.30 points with tirzepatide 5, 10, and 15 mg vs 1.86 with semaglutide 1 mg; weight loss 7.6, 9.3, and 11.2 kg vs 5.7 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/" } ], "faqs": [ { "q": "Wegovy vs Zepbound: which causes more weight loss?", "a": "Zepbound. In SURMOUNT-5, the direct comparison in 751 adults with obesity and no diabetes, tirzepatide (Zepbound's ingredient) produced 20.2% weight loss at 72 weeks versus 13.7% with semaglutide (Wegovy's ingredient), each at the maximum tolerated dose up to 15 mg and 2.4 mg. It is the only head-to-head obesity trial of the two.", "source_ids": [ "surmount-5" ] }, { "q": "Ozempic vs Mounjaro: which is better for type 2 diabetes?", "a": "On blood sugar and weight, Mounjaro. In SURPASS-2, tirzepatide 5, 10, and 15 mg lowered HbA1c by 2.01 to 2.30 percentage points versus 1.86 with semaglutide 1 mg over 40 weeks, and weight by 7.6 to 11.2 kg versus 5.7 kg; the trial did not test Ozempic's 2 mg dose. Ozempic has the longer heart record in type 2 diabetes (SUSTAIN-6) and a kidney outcomes indication, while tirzepatide was noninferior to dulaglutide for heart events in SURPASS-CVOT.", "source_ids": [ "surpass-2", "sustain-6", "fda-ozempic-label", "surpass-cvot" ] }, { "q": "Wegovy vs Mounjaro: what is the difference?", "a": "They are different molecules with different labels. Wegovy is semaglutide, labeled for weight management, cardiovascular risk reduction, and MASH. Mounjaro is tirzepatide, labeled for type 2 diabetes and cardiovascular risk reduction in type 2 diabetes, not for weight management. Tirzepatide's weight management label is Zepbound, and in SURMOUNT-5 tirzepatide produced 20.2% weight loss versus 13.7% with semaglutide.", "source_ids": [ "fda-wegovy-label", "fda-mounjaro-label", "fda-zepbound-label", "surmount-5" ] }, { "q": "Is semaglutide better for the heart?", "a": "In people with obesity but no diabetes, yes on current evidence: SELECT showed a 20% relative reduction in major adverse cardiovascular events with semaglutide, and Wegovy carries an FDA indication for that use, while Zepbound has none. In type 2 diabetes the gap is smaller: SURPASS-CVOT found tirzepatide noninferior to dulaglutide (hazard ratio 0.92), and the Mounjaro label now includes cardiovascular risk reduction in type 2 diabetes.", "source_ids": [ "select", "fda-wegovy-label", "fda-zepbound-label", "surpass-cvot", "fda-mounjaro-label" ] }, { "q": "Do they have different side effects?", "a": "The side effect profiles are largely the same: nausea, vomiting, diarrhea, and constipation that peak during dose escalation, plus the same boxed warning about thyroid C-cell tumors and the same contraindication for medullary thyroid carcinoma or MEN 2. In SURPASS-2 gastrointestinal events were similar in kind between the two drugs.", "source_ids": [ "fda-wegovy-label", "fda-zepbound-label", "surpass-2" ] }, { "q": "Can I switch from Wegovy to Zepbound?", "a": "Switching happens in practice but neither label includes a switching protocol, and neither SURMOUNT-5 nor SURPASS-2 studied it. The labels start tirzepatide at 2.5 mg weekly regardless of prior GLP-1 dose. Talk to the prescriber about timing and escalation rather than following an online schedule.", "source_ids": [ "fda-zepbound-label", "fda-wegovy-label" ] } ], "sources": [ { "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": "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": "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": "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": "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": "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" }, { "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" }, { "id": "fda-glp1-compounding", "type": "fda", "title": "FDA: concerns with unapproved GLP-1 drugs used for weight loss, including shortage resolution and compounding grace periods", "url": "https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "novocare", "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" }, { "id": "lillydirect", "type": "other", "title": "Manufacturer pricing information page for tirzepatide for weight management: list price and self-pay prices by dose, accessed 2026-09-22", "url": "https://pricinginfo.lilly.com/zepbound" }, { "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": "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": "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Wegovy vs Zepbound (semaglutide vs tirzepatide)", "description": "Wegovy vs Zepbound and Ozempic vs Mounjaro: the SURMOUNT-5 head-to-head result, heart data, side effects, FDA label doses, and cost, with sources.", "h1": "Wegovy vs Zepbound and Ozempic vs Mounjaro (semaglutide vs tirzepatide)", "headings": { "head-to-head": "Wegovy vs Zepbound: weight loss in the head-to-head trial" } } }, { "slug": "semax-vs-noopept", "a": "semax", "b": "noopept", "title": "Semax vs Noopept", "summary": "Semax and Noopept are both Russian nootropics with only small open label human studies, but they reach users very differently. Semax is an intranasal peptide that came off FDA Category 2 in April 2026 and was recommended for the 503A bulks list, so it may be prescribed and compounded. Noopept is an oral piracetam relative that has never been nominated for compounding and is sold in the US as a supplement ingredient, which is not a lawful use.", "verdict": { "winner": "a", "rationale": "The evidence is a tie: both are graded human observational from open Russian studies without placebo control (semax in stroke, Noopept in mild cognitive impairment after stroke or brain injury). Regulatory status breaks it. Semax has a pending path to lawful compounding after the July 2026 PCAC recommendation, while Noopept is not compoundable and its supplement sales are not an approved use, so product identity and purity are unverified.", "source_ids": [ "gusev-1997", "amelin-2011", "neznamov-2009", "fda-pcac-2026", "fda-cat2", "fda-compounding-qa" ] }, "dimensions": [ { "name": "What it is", "a": "Heptapeptide analog of ACTH fragment 4-10 with a stabilizing Pro-Gly-Pro tail.", "b": "Synthetic dipeptide-like compound (phenylacetyl proline-glycine ethyl ester) related to piracetam, metabolized to cycloprolylglycine.", "source_ids": [ "dolotov-2006", "ostrovskaya-2014" ] }, { "name": "Proposed mechanism", "a": "Raised hippocampal BDNF and trkB in rats after one intranasal dose; monoamine and anti-ischemic effects in rodents.", "b": "Raises BDNF and NGF in rodent hippocampus, enhances inhibitory transmission via alpha-7 nicotinic receptors on interneurons, and reduced tau hyperphosphorylation in a cell model.", "source_ids": [ "dolotov-2006", "kondratenko-2022", "ostrovskaya-2014" ] }, { "name": "Human evidence", "a": "Open comparative Russian studies in acute ischemic stroke and chronic cerebrovascular insufficiency; no blinding or placebo.", "b": "Open comparison with piracetam in mild cognitive disorders of vascular or traumatic origin, and an open study of 60 stroke patients reporting better MMSE scores after 2 months versus untreated controls.", "source_ids": [ "gusev-1997", "gusev-2005", "neznamov-2009", "amelin-2011" ] }, { "name": "Route", "a": "Intranasal drops (Russian product and most sold forms).", "b": "Oral tablet (Russian product) or capsule and powder (US supplement market).", "source_ids": [ "gusev-1997", "amelin-2011" ] }, { "name": "Doses in the literature", "a": "Intranasal 12 to 18 mg per day for 5 to 10 days in acute stroke; roughly 0.2 to 2 mg per day for cognitive uses.", "b": "10 mg orally twice daily (20 mg per day) for 2 months.", "source_ids": [ "gusev-1997", "amelin-2011" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended the 503A bulks list in July 2026; no final rule yet.", "b": "Never nominated for the 503A or 503B bulks lists and not on the Category 2 page; not compoundable. Sold as a supplement ingredient, which is not an approved use for a synthetic drug substance.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "fda-cat2", "fda-compounding-qa" ] }, { "name": "Access and cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "Sold online as an unapproved supplement that is not verified for identity or purity; no licensed pharmacy or telehealth channel.", "source_ids": [ "fda-pcac-2026", "fda-compounding-qa" ] }, { "name": "Reported side effects", "a": "Nasal irritation; anxiety, irritability, or insomnia reported anecdotally.", "b": "Irritability, sleep disturbance, and headache reported anecdotally; blood pressure increases in some patients in Russian reports.", "source_ids": [ "gusev-1997", "amelin-2011" ] }, { "name": "WADA status", "a": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "b": "Not named on the WADA Prohibited List; status unclear, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is semax or Noopept better for memory?", "a": "Neither has a placebo controlled trial for memory. Noopept's human data are in mild cognitive impairment after stroke or brain injury (better MMSE scores versus untreated controls in an open study of 60 patients); semax's are in stroke recovery. Evidence in healthy adults is absent for both.", "source_ids": [ "amelin-2011", "neznamov-2009", "gusev-1997" ] }, { "q": "Is Noopept a peptide?", "a": "Not strictly. It is a small synthetic dipeptide-like molecule related to piracetam that is metabolized to the natural dipeptide cycloprolylglycine. Semax is a true seven amino acid peptide.", "source_ids": [ "ostrovskaya-2014", "dolotov-2006" ] }, { "q": "Is it legal to buy Noopept as a supplement?", "a": "It is sold that way, but a synthetic drug substance approved as a medicine in Russia does not meet the definition of a dietary ingredient, so the sale is not an approved use and products are not verified for identity or purity. Noopept also cannot be compounded, because it has never been nominated for the bulks lists.", "source_ids": [ "fda-compounding-qa", "fda-cat2" ] }, { "q": "Can a US pharmacy compound semax?", "a": "Not from bulk today. Semax came off FDA Category 2 on April 15, 2026 and PCAC recommended it for the 503A bulks list in July 2026, but the recommendation is advisory: until FDA publishes a final rule it is not on the bulks list, a 503A pharmacy has no federal basis to compound it from bulk, and state boards cannot authorize what federal law does not.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are either banned in sport?", "a": "Neither is named on the WADA Prohibited List. Tested athletes should confirm with their anti-doping organization, because unapproved substances can fall under S0.", "source_ids": [ "wada-list" ] } ], "sources": [ { "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": "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": "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": "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": "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": "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": "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": "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": "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 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "semax-vs-selank", "a": "semax", "b": "selank", "title": "Semax vs Selank", "summary": "Semax and selank are sister Russian heptapeptides with the same weak evidence base, small open label studies published in Russian, but they are used for different things: semax for stroke recovery and cognition, selank for anxiety. Semax has the clearer US path, since it came off FDA Category 2 in April 2026 and was recommended for the 503A bulks list in July 2026. Selank is off Category 2 too, but its nomination was withdrawn and it was not recommended, so most pharmacies will not compound it.", "verdict": { "winner": "a", "rationale": "Both are graded human observational: neither has an indexed double blind placebo controlled trial, and both rely on studies from the developing Russian research groups. The tiebreaker is regulatory status. Semax was recommended by the Pharmacy Compounding Advisory Committee for the 503A bulks list in July 2026, while selank was not and sits in neither category after its nomination was withdrawn. If the goal is anxiety specifically, selank is the one studied for it, but approved anxiety treatments with real trials should come first.", "source_ids": [ "gusev-1997", "zozulya-2008", "medvedev-2014", "fda-503a-bulks", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "Heptapeptide analog of ACTH fragment 4-10 (Met-Glu-His-Phe-Pro-Gly-Pro); does not stimulate cortisol release.", "b": "Heptapeptide analog of tuftsin (Thr-Lys-Pro-Arg), an immune peptide fragment of IgG, extended with Pro-Gly-Pro.", "note": "Both use the same Pro-Gly-Pro tail for stability.", "source_ids": [ "dolotov-2006", "vyunova-2018" ] }, { "name": "Main use studied", "a": "Acute ischemic stroke recovery and chronic cerebrovascular insufficiency; cognitive and asthenic uses in Russian labeling.", "b": "Generalized anxiety disorder and neurasthenia.", "source_ids": [ "gusev-1997", "gusev-2005", "zozulya-2008" ] }, { "name": "Proposed mechanism", "a": "Raised hippocampal BDNF protein about 1.4 fold and trkB expression within hours of one intranasal dose in rats; monoamine and anti-ischemic effects in rodents.", "b": "Allosteric GABA-A modulation, inhibition of enkephalin degrading enzymes, and monoamine and BDNF effects in rodent and cell work.", "source_ids": [ "dolotov-2006", "vyunova-2018" ] }, { "name": "Human evidence", "a": "Open comparative Russian stroke studies (1997, 2005, 2018) reporting faster neurological recovery and fewer exacerbations; no blinding or placebo.", "b": "Small Russian anxiety studies (2008, 2014, 2015), including a comparison with phenazepam reporting similar anxiety relief with less sedation; no placebo controlled trial.", "source_ids": [ "gusev-1997", "gusev-2005", "gusev-2018", "zozulya-2008", "medvedev-2014", "medvedev-2015" ] }, { "name": "Doses in the literature", "a": "Intranasal 12 to 18 mg per day (1% solution) for 5 to 10 days in acute stroke; roughly 0.2 to 2 mg per day (0.1% solution) for cognitive uses.", "b": "Intranasal 0.15% solution at roughly 0.3 to 2.7 mg per day for 10 to 14 days.", "source_ids": [ "gusev-1997", "zozulya-2008" ] }, { "name": "Reported side effects", "a": "Nasal irritation; anxiety, irritability, or insomnia reported anecdotally at higher doses.", "b": "Nasal irritation; fatigue or drowsiness reported anecdotally; less sedation than phenazepam in the comparative study.", "source_ids": [ "gusev-1997", "medvedev-2014" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list in July 2026; no final rule yet.", "b": "Nomination withdrawn, so no longer in Category 2, but not on the bulks list and not recommended by PCAC in July 2026; most 503A pharmacies will not compound it.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Typical cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "No lawful compounded price: selank is not on the 503A bulks list and was not recommended by PCAC in July 2026.", "note": "Research chemical nasal sprays and vials are not lawful for human use.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "WADA status", "a": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "b": "Not named on the WADA Prohibited List; whether it falls under S0 (non-approved substances) is unclear, so tested athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "What is the difference between semax and selank?", "a": "Semax is built from a fragment of ACTH and was studied mainly for stroke recovery and cognition; selank is built from the immune peptide tuftsin and was studied mainly for anxiety. Both are intranasal Russian prescription peptides with the same stabilizing Pro-Gly-Pro tail.", "source_ids": [ "dolotov-2006", "gusev-1997", "zozulya-2008", "vyunova-2018" ] }, { "q": "Can semax and selank be used together?", "a": "No study has tested the combination, so any benefit or risk of using both is unknown. They are proposed to act on different systems, semax on BDNF and monoamines in rats and selank on GABA and enkephalin breakdown, which is the reasoning behind combined nasal products. Neither has FDA approval, and only semax was recommended for the 503A bulks list in July 2026, so there is no lawful US source for a combined product.", "source_ids": [ "dolotov-2006", "vyunova-2018", "fda-pcac-2026" ] }, { "q": "Which is better for anxiety?", "a": "Selank is the one studied for anxiety: small Russian studies reported reduced anxiety scores and effects similar to phenazepam with less sedation. None were placebo controlled, so the effect is not established by Western standards.", "source_ids": [ "zozulya-2008", "medvedev-2014" ] }, { "q": "Which is better for focus or memory?", "a": "Semax has the more relevant data, mostly stroke recovery studies and rat work showing increased hippocampal BDNF. No placebo controlled trial in healthy adults has tested either one for focus or memory.", "source_ids": [ "dolotov-2006", "gusev-1997", "gusev-2018" ] }, { "q": "Can I get semax or selank from a US pharmacy?", "a": "Semax was recommended for the 503A bulks list by the Pharmacy Compounding Advisory Committee in July 2026, so some pharmacies may compound it depending on the state board. Selank is off Category 2 but was not recommended, and most pharmacies will not make it. Neither is FDA approved.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026" ] }, { "q": "Are semax and selank allowed in sport?", "a": "Neither is named on the WADA Prohibited List. Because both are non-approved substances, S0 could apply, so tested athletes should confirm with their anti-doping organization before use.", "source_ids": [ "wada-list" ] } ], "sources": [ { "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": "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": "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": "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": "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": "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": "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": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 2, "seo": { "title": "Semax vs selank: differences, evidence, and legal status", "description": "Semax vs selank compared: what each nasal peptide was studied for, the strength of the Russian trials, side effects, and 2026 US legal status." } }, { "slug": "sermorelin-vs-cjc-1295", "a": "sermorelin", "b": "cjc-1295", "title": "Sermorelin vs CJC-1295", "summary": "Sermorelin is the better choice of the two GHRH analogs because it is the only one with a prior FDA approval, human trials that measured something beyond hormone levels, and a pathway by which 503A pharmacies dispense it under a prescription. CJC-1295 has the more impressive pharmacokinetics, with a single injection raising GH 2 to 10 fold for about a week and IGF-1 for 9 to 11 days in two small placebo controlled trials, but no trial ever measured body composition or any clinical outcome, development stopped in the late 2000s, and its FDA compounding nomination was withdrawn after a 2023 Category 2 listing. Both are prohibited by WADA under section S2.", "verdict": { "winner": "a", "rationale": "Both carry a human RCT evidence grade, but the content differs: sermorelin's trials include a 12 month pediatric growth study and a placebo controlled adult study with lean mass and skin thickness endpoints, while CJC-1295's two trials lasted 28 to 49 days and measured only GH and IGF-1. On regulation, sermorelin was FDA approved as Geref from 1990 to 2009 and FDA later confirmed the withdrawal was not for safety or effectiveness, which is the basis on which many 503A pharmacies compound it; CJC-1295 was placed in 503A Category 2 in September 2023 citing serious adverse events and is now a withdrawn nomination with no lawful basis for compounding.", "source_ids": [ "khorram-1997", "kirk-1994", "teichman-2006", "fr-geref-2013", "fda-503a-bulks", "wada-list" ] }, "dimensions": [ { "name": "Human evidence", "a": "Dose response in healthy men (Vance 1986), a 12 month open study in 18 children with idiopathic short stature (Kirk 1994), a single blind placebo controlled 5 month study in 19 adults aged 55 to 71 (Khorram 1997), plus the pediatric registration trials behind the 1997 Geref approval.", "b": "Two randomized, placebo controlled, double blind ascending dose trials of 28 and 49 days in healthy adults (Teichman 2006) and a single dose overnight sampling study in healthy men (Ionescu 2006). All endpoints were hormonal.", "source_ids": [ "vance-1986", "kirk-1994", "khorram-1997", "prakash-1999", "teichman-2006", "ionescu-2006" ] }, { "name": "Clinical outcomes measured", "a": "Height velocity rose from 4.8 to 7.2 cm per year in children; in older adults, skin thickness increased in both sexes, lean body mass and insulin sensitivity improved in men only, and sleep quality did not change.", "b": "None. No trial has measured body composition, strength, fat loss, sleep, or any clinical endpoint. The only outputs are GH and IGF-1 concentrations and a serum proteomic profile consistent with GH axis activation.", "source_ids": [ "kirk-1994", "khorram-1997", "teichman-2006", "sackmann-sala-2009" ] }, { "name": "Duration of action", "a": "Plasma half life of minutes; GH release is a single pulse after each injection, which is why the label used nightly dosing.", "b": "Half life of 5.8 to 8.1 days because the drug affinity complex binds serum albumin. GH stayed elevated 2 to 10 fold for 6 or more days and IGF-1 1.5 to 3 fold for 9 to 11 days after one dose, with trough GH up 7.5 fold but pulsatility preserved.", "note": "The version sold as CJC-1295 without DAC (modified GRF 1-29) lacks the albumin linker, has a half life of about 30 minutes, and has no published human trial under that name.", "source_ids": [ "prakash-1999", "teichman-2006", "ionescu-2006" ] }, { "name": "Dosing frequency in the literature", "a": "Geref pediatric label: 30 ug/kg subcutaneously once daily at bedtime. Adult trial: 10 ug/kg nightly for 16 weeks. Children in Kirk 1994: 20 ug/kg twice daily.", "b": "Single subcutaneous doses in ascending cohorts, with 30 or 60 ug/kg best tolerated, repeated weekly or every two weeks over 28 to 49 days. No maintenance regimen was ever established.", "source_ids": [ "prakash-1999", "khorram-1997", "kirk-1994", "teichman-2006" ] }, { "name": "Regulatory history", "a": "FDA approved as Geref for diagnosis (1990) and for pediatric idiopathic GH deficiency (1997); the sponsor discontinued it in 2008 and FDA withdrew the approvals in 2009. In 2013 FDA determined in the Federal Register that the withdrawal was not for safety or effectiveness. Not on Category 2 and not on the 503A bulks list.", "b": "Never approved anywhere. Programs in HIV lipodystrophy and GH deficiency were discontinued. Placed in 503A Category 2 on September 29, 2023 citing limited clinical data, peptide impurities, and serious adverse events; the nomination was later withdrawn and FDA's April 2026 update lists it under withdrawn nominations.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Compounding and access", "a": "Many 503A pharmacies compound sermorelin under a prescription on the basis of the former approval, commonly through telehealth clinics; whether that satisfies the approved drug component condition depends on the state board and the pharmacy. No FDA approved product is currently marketed.", "b": "No lawful basis for 503A or 503B compounding: no approved product, no bulks list entry, and a withdrawn nomination. Clinics that still advertise it are dispensing outside FDA's stated categories.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "name": "Side effects in trials", "a": "Injection site pain and redness, facial flushing, headache, dizziness; transient hyperlipidemia in the adult trial; rising fasting glucose and insulin in children; antibody formation without loss of effect in the pediatric program.", "b": "Injection site reactions, flushing, headache, and transient warmth in the 2006 trials with no serious adverse reactions; FDA's Category 2 evaluation cited increased heart rate and a systemic vasodilatory reaction among serious adverse events. Risks of week long IGF-1 elevation have not been studied.", "source_ids": [ "khorram-1997", "kirk-1994", "prakash-1999", "teichman-2006", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S2, which names GHRH and its analogues including sermorelin.", "b": "Prohibited at all times under section S2, which names CJC-1295 specifically.", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "Compounded only, paid in cash through telehealth clinics that include the visit; there is no branded product. Dated prices are on the sermorelin cost page.", "b": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is CJC-1295 just a longer acting sermorelin?", "a": "Chemically, close to it. Both are GHRH(1-29) analogs, but CJC-1295 adds four stabilizing substitutions and a drug affinity complex that binds albumin, stretching the half life from minutes to 5.8 to 8.1 days. That changes the pharmacology from a nightly GH pulse to a week of elevated trough GH and IGF-1, and no trial has established whether that is better or worse for any outcome.", "source_ids": [ "teichman-2006", "ionescu-2006", "prakash-1999" ] }, { "q": "Which has better evidence for body composition?", "a": "Sermorelin, narrowly. The only trial with a body composition endpoint is Khorram 1997, where 16 weeks of nightly sermorelin increased lean mass and insulin sensitivity in men but not women, with no change in sleep. CJC-1295 has never been tested for body composition at all.", "source_ids": [ "khorram-1997", "teichman-2006" ] }, { "q": "Why can pharmacies compound sermorelin but not CJC-1295?", "a": "Sermorelin was an FDA approved drug (Geref) until 2009, and FDA confirmed in 2013 that it was not withdrawn for safety or effectiveness; many pharmacies treat that as satisfying the approved drug component pathway. CJC-1295 was never approved, was placed in 503A Category 2 in 2023 for safety concerns, and its nomination was then withdrawn, leaving no lawful basis.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "q": "Do they have the same side effects?", "a": "Largely the same GHRH class effects: injection site reactions, flushing, and headache. Sermorelin's trials also recorded transient hyperlipidemia in adults and rising glucose in children. For CJC-1295, FDA cited increased heart rate and a systemic vasodilatory reaction among the serious adverse events in its Category 2 evaluation, and the effects of sustained IGF-1 elevation over months are unstudied.", "source_ids": [ "khorram-1997", "kirk-1994", "fda-503a-bulks" ] }, { "q": "Are both banned for athletes?", "a": "Yes. WADA section S2 prohibits GHRH and its analogues at all times and names both sermorelin and CJC-1295.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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 sermorelin and CJC-1295)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2 }, { "slug": "sermorelin-vs-ipamorelin", "a": "sermorelin", "b": "ipamorelin", "title": "Sermorelin vs ipamorelin", "summary": "Sermorelin has the stronger case: it was once FDA approved (Geref), it has small human trials showing higher growth hormone and IGF-1, and many 503A pharmacies still compound it because FDA found the approval was not withdrawn for safety reasons. Ipamorelin has no human trial for any growth hormone use, only one small IV pharmacology study showing growth hormone release in healthy men; its only randomized human trial, for postoperative ileus, found no benefit, and it has no lawful basis for compounding after its 2023 Category 2 listing and withdrawn nomination. They act on different receptors, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "Sermorelin is graded human_rct on small studies (a 19 person, 16 week adult trial and pediatric growth data behind its former approval) and has a defensible compounding pathway, while ipamorelin is graded animal_only for its marketed uses and sits outside every FDA compounding category after its nomination was withdrawn. Neither has evidence for adult fat loss, muscle gain, or anti-aging, so the win is about evidence quality and legality, not a proven benefit.", "source_ids": [ "khorram-1997", "kirk-1994", "fr-geref-2013", "beck-2014", "raun-1998", "fda-503a-bulks", "gobburu-1999" ] }, "dimensions": [ { "name": "Mechanism", "a": "GHRH receptor agonist: the first 29 amino acids of growth hormone releasing hormone, acting upstream on pituitary somatotrophs.", "b": "Ghrelin receptor (GHS-R1a) agonist: a five amino acid growth hormone secretagogue acting through a separate pathway from GHRH.", "note": "Because the receptors differ, the two are often marketed together, but no human trial has tested the combination.", "source_ids": [ "vance-1986", "raun-1998", "camanni-1998" ] }, { "name": "Evidence grade", "a": "Human RCT (small): single blind, placebo controlled 16 week trial in 19 adults aged 55 to 71 raised nocturnal GH and IGF-1.", "b": "Animal only for marketed uses: GH release in rats and pigs; the only human RCT (117 adults, intravenous, postoperative ileus) found no significant benefit.", "source_ids": [ "khorram-1997", "raun-1998", "beck-2014" ] }, { "name": "Human outcomes measured", "a": "Higher IGF-1 and skin thickness in both sexes; lean mass and insulin sensitivity gains in men only; sleep unchanged. Children with short stature grew 7.2 versus 4.8 cm per year.", "b": "Time to first tolerated meal after bowel surgery 25.3 versus 32.6 hours on placebo (p = 0.15). No human GH, IGF-1, or body composition outcome published for subcutaneous use.", "source_ids": [ "khorram-1997", "kirk-1994", "beck-2014" ] }, { "name": "Hormonal selectivity", "a": "Response limited by somatostatin tone and pituitary capacity, so GH cannot reach levels seen with injected recombinant GH.", "b": "In animals it released GH without raising ACTH, cortisol, prolactin, LH, FSH, or TSH, even at 200 times the GH ED50.", "source_ids": [ "walker-2006", "raun-1998" ] }, { "name": "Regulatory history", "a": "Approved as Geref (diagnostic 1990, pediatric GH deficiency 1997); discontinued, approvals withdrawn in 2009; FDA determined in 2013 the withdrawal was not for safety or effectiveness.", "b": "Never approved anywhere. Placed on the 503A Category 2 list in September 2023; nominations withdrawn in 2024 and listed as a withdrawn nomination in the April 2026 update.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "name": "Compounding status", "a": "Not on Category 2 or the bulks list; many 503A pharmacies compound it on the basis of the former approval, a reading that depends on the state board.", "b": "No active nomination, not on the bulks list, not an approved drug component: no lawful basis for 503A or 503B compounding.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "name": "Literature dosing", "a": "Geref label: 30 ug/kg subcutaneously at bedtime in children; adult trial used 10 ug/kg nightly for 16 weeks.", "b": "Not established for GH use; the only human trial used 0.03 mg/kg intravenously twice daily for up to 7 days after surgery.", "source_ids": [ "prakash-1999", "khorram-1997", "beck-2014" ] }, { "name": "Typical cost", "a": "Compounded only, paid in cash through telehealth clinics that include the visit; there is no branded product. Dated prices are on the sermorelin cost page.", "b": "Not available through licensed channels; ipamorelin is not on the 503A bulks list.", "note": "Prices at the verification date. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks", "fr-geref-2013" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which has better evidence, sermorelin or ipamorelin?", "a": "Sermorelin. It has small human trials showing higher GH and IGF-1 (including a 16 week adult trial) and pediatric growth data that supported its former FDA approval. Ipamorelin has no human trial for any GH related use, only one small IV pharmacology study showing growth hormone release in healthy men; its only randomized human trial, for postoperative ileus, was negative.", "source_ids": [ "khorram-1997", "kirk-1994", "beck-2014", "gobburu-1999" ] }, { "q": "Can a pharmacy legally compound either one?", "a": "Sermorelin is widely compounded by 503A pharmacies on the basis of its former approval, which FDA confirmed was not withdrawn for safety reasons, though acceptability depends on the state board. Ipamorelin has no lawful basis: its nomination was withdrawn after a 2023 Category 2 listing and it is not on the bulks list.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks" ] }, { "q": "Does either help with fat loss or muscle gain?", "a": "Not on current evidence. Sermorelin's adult trial found a small lean mass gain in men only and no change in women; ipamorelin has never been tested for body composition in humans.", "source_ids": [ "khorram-1997", "beck-2014" ] }, { "q": "Why are they often sold together?", "a": "They stimulate GH through different receptors (GHRH versus ghrelin), and reviews of the GHRP class describe synergy with GHRH on GH release. No trial has tested sermorelin and ipamorelin together, so the benefit and safety of the combination are unknown.", "source_ids": [ "camanni-1998", "raun-1998" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are prohibited at all times under WADA section S2: sermorelin as a GHRH analog and ipamorelin as a growth hormone secretagogue.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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, and withdrawn nominations)", "url": "https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, and growth hormone secretagogues)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Sermorelin vs ipamorelin: evidence, cost, and legality", "description": "Sermorelin vs ipamorelin: a formerly approved GHRH analog against an unapproved ghrelin mimetic, compared on evidence and legality.", "h1": "Sermorelin vs ipamorelin (ipamorelin vs sermorelin)" } }, { "slug": "sermorelin-vs-mk-677", "a": "sermorelin", "b": "mk-677", "title": "Sermorelin vs MK-677 (ibutamoren)", "summary": "Sermorelin is the more defensible choice: it is a GHRH analog that once held FDA approval, it is not on any FDA Category 2 list, and it can be compounded by a licensed 503A pharmacy on a prescription. MK-677 (ibutamoren) has more and larger randomized trials, but it has never been approved, a hip fracture trial was stopped for a possible heart failure signal, and FDA placed it in both 503A and 503B Category 2, so there is no lawful US source. Both raise growth hormone and IGF-1 through different receptors, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "MK-677 has the larger evidence base (including a 2 year, 65 person randomized trial showing about 1.1 kg more fat free mass than placebo), but that trial also showed higher fasting glucose and reduced insulin sensitivity with no strength or function benefit, and a phase 2b hip fracture trial was terminated for a possible congestive heart failure signal, which is the basis of FDA's Category 2 listing. Sermorelin has smaller and older human data but a former FDA approval, a Federal Register finding that it was not withdrawn for safety, and a lawful compounding path. Between an option with a legal channel and no heart failure signal and one with neither, sermorelin wins.", "source_ids": [ "nass-2008", "adunsky-2011", "fda-category-2", "khorram-1997", "fr-geref-2013" ] }, "dimensions": [ { "name": "Mechanism", "a": "GHRH receptor agonist (the 1-29 fragment of growth hormone releasing hormone). Stimulates pulsatile GH release from the pituitary, limited by somatostatin tone.", "b": "Non peptide ghrelin receptor (GHS-R1a) agonist. Amplifies GH pulse amplitude without changing pulse frequency and, as a ghrelin mimetic, increases hunger.", "note": "Different receptors, same end point: more pituitary GH and higher IGF-1.", "source_ids": [ "khorram-1997", "chapman-1996" ] }, { "name": "Human evidence", "a": "Small and older: a 5 month single blind placebo controlled trial in 19 adults aged 55 to 71 raised nocturnal GH and IGF-1 and skin thickness, with lean mass and insulin sensitivity gains in men only. A 12 month open study in 18 short children raised height velocity from 4.8 to 7.2 cm per year.", "b": "Several randomized placebo controlled trials: 2 years in 65 older adults (about 1.1 kg more fat free mass, no strength or function benefit), 8 weeks in 24 obese men (about 3 kg more fat free mass, no fat loss), and 12 months in 563 people with Alzheimer disease (no clinical effect).", "source_ids": [ "khorram-1997", "kirk-1994", "nass-2008", "svensson-1998", "sevigny-2008" ] }, { "name": "Key safety signal", "a": "Injection site reactions, flushing, and headache in the pediatric program; transient hyperlipidemia in the adult trial. No trial was stopped for safety.", "b": "A phase 2b hip fracture trial was terminated early for a possible congestive heart failure signal. The 2 year trial showed higher fasting glucose (about 0.3 mmol/L), reduced insulin sensitivity, edema, and muscle pain.", "source_ids": [ "prakash-1999", "khorram-1997", "adunsky-2011", "nass-2008" ] }, { "name": "FDA and compounding status", "a": "Formerly FDA approved as Geref (1990 diagnostic, 1997 pediatric GH deficiency); withdrawn by the sponsor, with a 2013 Federal Register finding that it was not withdrawn for safety or effectiveness. Not on the 503A Category 2 list; many 503A pharmacies compound it on a prescription.", "b": "Never FDA approved. Placed in 503B Category 2 in December 2022 and 503A Category 2 in September 2023 for the heart failure signal, and still listed as of April 2026, so licensed pharmacies cannot lawfully compound it.", "source_ids": [ "fr-geref-2013", "fda-503a-bulks", "fda-category-2" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection, usually nightly at bedtime; plasma half life of minutes.", "b": "Oral capsule or tablet once daily; long acting.", "source_ids": [ "khorram-1997", "nass-2008" ] }, { "name": "Doses used in the literature", "a": "Geref label: 30 ug/kg subcutaneously once daily at bedtime in children. Adult trial: 10 ug/kg nightly for 16 weeks. No established adult anti-aging dose.", "b": "25 mg orally once daily in the main trials, with 2 mg and 50 mg arms in early studies. These are research doses, not an approved regimen.", "source_ids": [ "prakash-1999", "khorram-1997", "nass-2008", "chapman-1996" ] }, { "name": "Effect on appetite and glucose", "a": "No appetite effect reported. Fasting glucose and insulin rose during pediatric treatment; insulin sensitivity improved in older men in the adult trial.", "b": "Increased appetite is the most common effect across trials, and glucose control worsens with long term use.", "source_ids": [ "kirk-1994", "khorram-1997", "nass-2008" ] }, { "name": "WADA status", "a": "Prohibited at all times under S2 (GHRH and its analogues).", "b": "Prohibited at all times under S2 (ibutamoren is named as a GH secretagogue).", "note": "Neither is permitted for tested athletes.", "source_ids": [ "wada-list" ] }, { "name": "Typical cost and access", "a": "Compounded only, paid in cash through telehealth clinics that include the visit; there is no branded product. Dated prices are on the sermorelin cost page.", "b": "No lawful US channel. Products sold as research chemicals or supplements are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is MK-677 stronger than sermorelin?", "a": "No trial has compared them directly. MK-677 has larger and longer randomized trials showing sustained IGF-1 increases and about 1.1 kg more fat free mass than placebo over 2 years, but without strength or function gains. Sermorelin's human data are smaller and older. Stronger GH stimulation is not the same as better outcomes, and MK-677 carries a heart failure signal.", "source_ids": [ "nass-2008", "khorram-1997", "adunsky-2011" ] }, { "q": "Can a doctor prescribe MK-677?", "a": "Not through a lawful US pharmacy channel. FDA placed ibutamoren in both 503A and 503B Category 2, so compounding pharmacies and outsourcing facilities cannot lawfully make it, and it has never been approved. Sermorelin, by contrast, is compounded by 503A pharmacies on prescription.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Why is MK-677 on the FDA Category 2 list?", "a": "FDA cited the potential for congestive heart failure, based on a phase 2b trial in older adults recovering from hip fracture that was stopped early for that signal. Long term use also raised fasting glucose and reduced insulin sensitivity in a 2 year trial.", "source_ids": [ "fda-category-2", "adunsky-2011", "nass-2008" ] }, { "q": "Was sermorelin ever FDA approved?", "a": "Yes. Geref (sermorelin acetate) was approved as a diagnostic in 1990 and for idiopathic GH deficiency in children in 1997. The sponsor discontinued it and the approvals were withdrawn in 2009, and in 2013 FDA determined in the Federal Register that it was not withdrawn for reasons of safety or effectiveness.", "source_ids": [ "fr-geref-2013", "prakash-1999" ] }, { "q": "Can athletes use either one?", "a": "No. Both are prohibited at all times on the WADA Prohibited List under S2: sermorelin as a GHRH analogue and ibutamoren as a named GH secretagogue.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "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 (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 peptide hormones, growth factors, related substances and mimetics (GHRH analogues and GH secretagogues including ibutamoren)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2 }, { "slug": "sermorelin-vs-tesamorelin", "a": "sermorelin", "b": "tesamorelin", "title": "Sermorelin vs tesamorelin", "summary": "Both are growth hormone releasing hormone analogs, but tesamorelin has far stronger evidence and a current FDA approval: in two phase 3 trials of 806 people with HIV and excess abdominal fat, it cut visceral fat by 15.4% relative to placebo at 26 weeks, and it is sold as Egrifta WR and Egrifta SV. Sermorelin's adult evidence is a single 19 person trial showing higher IGF-1, and its former approval (Geref) was withdrawn in 2009. Neither is proven for fat loss or anti-aging in people without HIV, and both are prohibited in sport.", "verdict": { "winner": "b", "rationale": "Tesamorelin wins on evidence (large phase 3 RCTs with a body composition endpoint, plus a 61 person RCT showing a 37% relative drop in liver fat in HIV) and on regulatory status (FDA approved since 2010, and Egrifta WR is available by prescription). Sermorelin's human data are small and hormonal, and it has had no marketed FDA approved product since 2009. The win applies to the approved HIV indication; off label use in people without HIV rests on one small trial for tesamorelin and none for sermorelin.", "source_ids": [ "falutz-2010", "stanley-2019", "egrifta-label", "makimura-2012", "khorram-1997", "fr-geref-2013" ] }, "dimensions": [ { "name": "Molecule", "a": "First 29 amino acids of human GHRH; plasma half life of minutes.", "b": "Full 44 amino acid GHRH analog with an N-terminal trans-3-hexenoic acid group that resists dipeptidyl peptidase cleavage, extending action.", "source_ids": [ "vance-1986", "egrifta-label" ] }, { "name": "Best human evidence", "a": "Single blind, placebo controlled trial in 19 adults aged 55 to 71 for 16 weeks: higher nocturnal GH and IGF-1, thicker skin, lean mass and insulin sensitivity gains in men only.", "b": "Pooled phase 3 trials in 806 adults with HIV: visceral fat minus 24 versus plus 2 cm2 at 26 weeks (treatment effect minus 15.4%) and triglycerides minus 37 versus plus 6 mg/dL.", "source_ids": [ "khorram-1997", "falutz-2010" ] }, { "name": "Liver and metabolic evidence", "a": "No liver or visceral fat trial; transient hyperlipidemia in the adult trial.", "b": "HIV with fatty liver (61 adults, 12 months): hepatic fat fraction down an absolute 4.1% (37% relative); 35% versus 4% reached normal liver fat, with no glucose or HbA1c difference.", "source_ids": [ "khorram-1997", "stanley-2019" ] }, { "name": "FDA status", "a": "No currently approved product. Geref was approved in 1990 (diagnostic) and 1997 (pediatric GH deficiency), withdrawn in 2009; FDA found in 2013 this was not for safety or effectiveness.", "b": "FDA approved as Egrifta (2010), Egrifta SV (2019), and Egrifta WR (2025) to reduce excess abdominal fat in adults with HIV associated lipodystrophy.", "source_ids": [ "fr-geref-2013", "dailymed-egrifta-wr" ] }, { "name": "Compounding status", "a": "Not on Category 2 or the bulks list; 503A pharmacies compound it based on the former approval, a reading that depends on the state board.", "b": "Biologic since March 2020 (BLA 022505), so it is not eligible for 503A or 503B compounding; Egrifta WR by prescription is the only lawful product.", "source_ids": [ "fda-503a-bulks", "fda-compounding-qa", "fda-biologics-transition" ] }, { "name": "Label or literature dosing", "a": "Geref label: 30 ug/kg subcutaneously at bedtime in children. Adult trial: 10 ug/kg nightly.", "b": "FDA label: Egrifta WR 1.28 mg or Egrifta SV 1.4 mg injected under the skin of the abdomen once daily (the formulations are not substitutable); the phase 3 trials used 2 mg daily of the original Egrifta. Effect fades after stopping.", "source_ids": [ "prakash-1999", "khorram-1997", "dailymed-egrifta-wr", "dailymed-egrifta-sv", "falutz-2010" ] }, { "name": "Side effects", "a": "Injection site reactions, flushing, headache; rising fasting glucose and insulin in children; antibodies without apparent loss of effect.", "b": "Arthralgia (about 13%), injection site reactions, peripheral edema, myalgia, paresthesia; label advises monitoring glucose and IGF-1.", "source_ids": [ "prakash-1999", "kirk-1994", "egrifta-label" ] }, { "name": "Typical cost", "a": "Compounded only, paid in cash through telehealth clinics that include the visit; there is no branded product. Dated prices are on the sermorelin cost page.", "b": "Egrifta WR has no published list price; one retail cash listing put a 28 day kit at about 10,709 USD (checked 2026-09-22). Compounded tesamorelin has no lawful price because tesamorelin is a biologic; dated prices are on the tesamorelin cost page.", "note": "Prices at the verification date change often.", "source_ids": [ "fr-geref-2013", "price-listing-egrifta-wr", "dailymed-egrifta-wr", "fda-biologics-transition" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is tesamorelin just a stronger sermorelin?", "a": "Both activate the GHRH receptor, but tesamorelin is the full 44 amino acid hormone with a protective chemical group, so it lasts longer, and it has been tested in large phase 3 trials. Sermorelin is the 29 amino acid fragment with a half life of minutes.", "source_ids": [ "egrifta-label", "vance-1986", "falutz-2010" ] }, { "q": "Tesamorelin vs sermorelin: which works better?", "a": "Tesamorelin, on the evidence. It cut visceral fat by 15.4% relative to placebo in 806 adults with HIV and by about 35 cm2 in a 60 person trial of abdominal obesity without HIV. Sermorelin's best adult trial had 19 people and measured hormone levels, skin thickness, and lean mass in men, not fat loss. Only tesamorelin has a current FDA approval.", "source_ids": [ "falutz-2010", "makimura-2012", "khorram-1997", "dailymed-egrifta-wr" ] }, { "q": "Which is better for belly fat?", "a": "Tesamorelin is the only one with trial evidence: in people with HIV it reduced visceral fat by 15.4% relative to placebo over 26 weeks. Outside HIV, one 60 person trial in abdominal obesity with reduced growth hormone secretion found a similar visceral fat drop with tesamorelin. No trial has tested sermorelin for visceral fat.", "source_ids": [ "falutz-2010", "makimura-2012", "khorram-1997" ] }, { "q": "Is either FDA approved?", "a": "Tesamorelin is, as Egrifta WR and Egrifta SV for HIV associated abdominal fat. Sermorelin was approved as Geref but the approvals were withdrawn in 2009; FDA later determined that was not for safety or effectiveness reasons.", "source_ids": [ "dailymed-egrifta-wr", "fr-geref-2013" ] }, { "q": "Why is compounded sermorelin so much cheaper than Egrifta?", "a": "Branded Egrifta WR has no published list price, and one retail cash listing put a 28 day kit at about 10,709 USD (checked 2026-09-22). Compounded sermorelin is paid in cash at a small fraction of that; it is not an FDA approved formulation and is not tested the way a branded product is. Compounded tesamorelin is not a lawful option at any price, because tesamorelin is a biologic and biologics cannot be compounded.", "source_ids": [ "price-listing-egrifta-wr", "fda-compounding-qa", "fda-biologics-transition" ] }, { "q": "Can athletes use either?", "a": "No. Both are growth hormone releasing hormone analogs prohibited at all times under WADA section S2.", "source_ids": [ "wada-list" ] } ], "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": "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": "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, including sermorelin and tesamorelin)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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": "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": "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Tesamorelin vs sermorelin: evidence, cost, and legality", "description": "Tesamorelin vs sermorelin: two GHRH analogs compared on trial evidence, FDA status, label dosing, side effects, and cost.", "h1": "Sermorelin vs tesamorelin (tesamorelin vs sermorelin)" } }, { "slug": "survodutide-vs-mazdutide", "a": "survodutide", "b": "mazdutide", "title": "Survodutide vs mazdutide", "summary": "Survodutide and mazdutide are both once weekly GLP-1 and glucagon dual agonists. Mazdutide is further along: approved in China for weight management and type 2 diabetes, with 14.0% weight loss at 48 weeks in GLORY-1 and phase 3 wins over dulaglutide and semaglutide in diabetes. Survodutide produced 12.2% to 13.0% at 76 weeks in SYNCHRONIZE-1 and has the stronger liver (MASH) data. Neither is FDA approved.", "verdict": { "winner": "b", "rationale": "Mazdutide has more phase 3 evidence, including two active-comparator diabetes trials (DREAMS-2 against dulaglutide and DREAMS-3 against semaglutide), a regulatory approval in China, and a lower adverse event discontinuation rate in GLORY-1. Survodutide's advantage is its biopsy-based MASH phase 2 result. No trial compares them directly, and in the United States both remain trial-only.", "source_ids": [ "glory-1", "dreams-2", "dreams-3-topline", "mazdutide-china-obesity-approval", "synchronize-1", "survodutide-mash-phase2" ] }, "dimensions": [ { "name": "Mechanism", "a": "Glucagon analog engineered to also activate the GLP-1 receptor.", "b": "Oxyntomodulin analog that activates the GLP-1 and glucagon receptors.", "note": "Same receptor pair, different parent molecules and receptor balance.", "source_ids": [ "synchronize-1", "glory-1" ] }, { "name": "Phase 3 weight loss", "a": "12.2% (3.6 mg) and 13.0% (6.0 mg) versus 5.4% on placebo at 76 weeks (SYNCHRONIZE-1, 725 adults, treatment regimen estimand).", "b": "11.0% (4 mg) and 14.0% (6 mg) versus 0.3% gain on placebo at 48 weeks (GLORY-1, 610 Chinese adults).", "note": "The placebo arms differ a lot (5.4% loss versus 0.3% gain), so the drug minus placebo gap is wider for mazdutide.", "source_ids": [ "synchronize-1", "glory-1" ] }, { "name": "Type 2 diabetes evidence", "a": "Phase 2 (413 adults, 16 weeks): HbA1c down up to 1.71 points; weight loss greater than semaglutide 1 mg at 1.8 mg and above.", "b": "Phase 3 DREAMS-2 (731 adults): superior to dulaglutide 1.5 mg on HbA1c and weight at 28 weeks. DREAMS-3 (349 adults): superior to semaglutide 1 mg on a combined HbA1c and weight goal (manufacturer topline).", "source_ids": [ "survodutide-t2d-phase2", "dreams-2", "dreams-3-topline" ] }, { "name": "Liver disease evidence", "a": "Phase 2 MASH trial (293 adults, biopsy confirmed): improvement without worsening fibrosis in 47% to 62% versus 14% on placebo at 48 weeks.", "b": "No biopsy-based MASH trial has reported.", "source_ids": [ "survodutide-mash-phase2", "glory-1" ] }, { "name": "Tolerability", "a": "Gastrointestinal symptoms in 80.9% to 89.7% versus 47.9% on placebo in SYNCHRONIZE-1.", "b": "Discontinuation for adverse events 1.5% or less in GLORY-1; gastrointestinal events higher than dulaglutide in DREAMS-2.", "source_ids": [ "synchronize-1", "glory-1", "dreams-2" ] }, { "name": "Regulatory status", "a": "Investigational; not approved by any regulator and not eligible for US compounding.", "b": "Approved in China (June 2025 weight management, September 2025 type 2 diabetes). Not FDA approved and not eligible for US compounding.", "source_ids": [ "fda-503a-bulks", "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval" ] }, { "name": "WADA status", "a": "Prohibited under section S0 (non-approved substances).", "b": "Not named on the list; with approval in China, section S0 may not apply. Confirm with the relevant anti-doping organization.", "source_ids": [ "wada-list", "mazdutide-china-obesity-approval" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Are survodutide and mazdutide the same kind of drug?", "a": "Yes, both activate the GLP-1 and glucagon receptors and are dosed once weekly. Survodutide is built from glucagon, mazdutide from oxyntomodulin.", "source_ids": [ "synchronize-1", "glory-1" ] }, { "q": "Which one causes more weight loss?", "a": "Their phase 3 results are similar in absolute terms (13.0% at 76 weeks for survodutide 6.0 mg, 14.0% at 48 weeks for mazdutide 6 mg), but mazdutide's placebo group gained weight while survodutide's lost 5.4%, so mazdutide's placebo-adjusted effect was larger. They have not been compared directly.", "source_ids": [ "synchronize-1", "glory-1" ] }, { "q": "Which is better for fatty liver disease?", "a": "Survodutide has the stronger liver evidence, a biopsy-based phase 2 MASH trial with improvement in up to 62% versus 14% on placebo. Mazdutide has not reported a comparable trial.", "source_ids": [ "survodutide-mash-phase2" ] }, { "q": "Can I get either one in the US?", "a": "No lawful path exists outside a clinical trial. Neither is FDA approved or eligible for compounding; mazdutide is approved only in China.", "source_ids": [ "fda-503a-bulks", "mazdutide-china-obesity-approval" ] } ], "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": "dreams-2", "type": "pubmed", "title": "Guo L et al. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature 2026 (DREAMS-2)", "url": "https://pubmed.ncbi.nlm.nih.gov/41407860/", "pmid": "41407860", "year": 2026 }, { "id": "dreams-3-topline", "type": "other", "title": "Manufacturer press release: DREAMS-3 phase 3 head-to-head results of mazdutide versus semaglutide (October 26, 2025), accessed 2026-09-22", "url": "https://www.prnewswire.com/news-releases/innovents-mazdutide-shows-superiority-in-glycemic-control-with-weight-loss-over-semaglutide-in-a-head-to-head-phase-3-clinical-trial-dreams-3-302594633.html", "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), accessed 2026-09-22", "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": "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": "survodutide-t2d-phase2", "type": "pubmed", "title": "Bluher M et al. Dose-response effects on HbA1c and bodyweight reduction of survodutide compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38095657/", "pmid": "38095657", "year": 2024 }, { "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" }, { "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), accessed 2026-09-22", "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 }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "tb-500-vs-ghk-cu", "a": "tb-500", "b": "ghk-cu", "title": "TB-500 vs GHK-Cu", "summary": "GHK-Cu has the better evidence and the easier legal path for its main use: small human studies support topical GHK-Cu creams for aged skin, and those creams are sold lawfully as cosmetics. TB-500 has no human trial of the injectable; its parent peptide, thymosin beta-4, has strong rodent wound and cardiac data and one human eye drop trial that missed its primary endpoints. Both are wound and repair peptides in animals, both lack human data for injection, and TB-500 is named on the WADA Prohibited List while GHK-Cu is not.", "verdict": { "winner": "b", "rationale": "GHK-Cu is graded human observational on the strength of controlled topical cosmetic studies, and topical products are lawful without a prescription. Injected TB-500 is graded animal only; the one human randomized trial of thymosin beta-4 used eye drops for dry eye and did not meet its primary endpoints. On regulatory status TB-500 is a step ahead for injection (PCAC recommended it for the 503A bulks list in July 2026, while injectable GHK-Cu was not reviewed), but that does not change the evidence gap, and TB-500 is explicitly banned in sport.", "source_ids": [ "pickart-2015", "sosne-2015", "fda-cosmetics-vs-drugs", "fda-pcac-2026", "wada-list-s2" ] }, "dimensions": [ { "name": "What it is", "a": "Synthetic thymosin beta-4 (43 amino acids) or a fragment of it; the identity of products sold as TB-500 is not verified.", "b": "Naturally occurring copper binding tripeptide (glycyl-histidyl-lysine) found in human plasma, saliva, and urine.", "source_ids": [ "goldstein-2012", "pickart-2008" ] }, { "name": "Evidence grade", "a": "Animal only for the injectable. One human phase 2 eye drop trial (72 adults, dry eye) missed both primary endpoints; phase 1 intravenous studies in healthy volunteers tested safety only.", "b": "Human observational for topical use: small controlled cosmetic studies of creams in aged skin. No human data for injection.", "source_ids": [ "sosne-2015", "pickart-2015", "ruff-2010" ] }, { "name": "Strongest animal evidence", "a": "Rat full thickness wounds healed faster (reepithelialization up 42% at day 4 and 61% at day 7); improved cardiac function after coronary ligation in mice.", "b": "Faster skin wound healing in rats, mice, pigs, and dogs, plus hair follicle, bone, and gut healing in rodents.", "source_ids": [ "malinda-1999", "bock-marquette-2004", "pickart-2018" ] }, { "name": "Proposed mechanism", "a": "Binds G-actin to drive cell migration and activates the ILK and Akt cell survival pathway; reduces inflammation and scarring in animals.", "b": "Delivers copper to cells, recruits repair cells, and increases collagen, elastin, and glycosaminoglycan synthesis; suppresses NF-kB and TNF-alpha in models.", "source_ids": [ "bock-marquette-2004", "goldstein-2012", "pickart-2008" ] }, { "name": "Routes with human data", "a": "Topical eye drops only (investigational). Subcutaneous or intramuscular injection as sold has no human data.", "b": "Topical cream or serum only. Subcutaneous injection as sold has no human data.", "source_ids": [ "sosne-2015", "pickart-2015" ] }, { "name": "FDA and compounding status", "a": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list in July 2026; no final rule yet.", "b": "Injectable nomination withdrawn, so no longer in Category 2, but not on the bulks list and not reviewed by PCAC. Topical is a lawful cosmetic ingredient when no drug claims are made.", "source_ids": [ "fda-503a-bulks", "fda-pcac-2026", "fda-cosmetics-vs-drugs" ] }, { "name": "WADA status", "a": "Prohibited at all times under S2; thymosin beta-4 and TB-500 are named on the list.", "b": "Not named. Injected GHK-Cu may fall under S0 as a non-approved substance, so its status is unclear; topical cosmetic use is not a recognized concern.", "source_ids": [ "wada-list-s2", "wada-list-s0" ] }, { "name": "Typical cost", "a": "No lawful compounded price: not on the 503A bulks list, and advertised clinic prices are not a comparable price.", "b": "Topical cosmetic serums and creams roughly 20 to 100 USD per bottle. No lawful compounded price for injectable GHK-Cu, which is not on the 503A bulks list.", "source_ids": [ "fda-503a-bulks", "fda-cosmetics-vs-drugs" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for wound healing, TB-500 or GHK-Cu?", "a": "Both accelerate wound healing in animals, and neither has a human trial of the injectable form for wounds. Thymosin beta-4 has strong rat wound data, and GHK-Cu has animal wound data across several species plus human topical cosmetic studies. For a real wound, standard wound care comes first.", "source_ids": [ "malinda-1999", "pickart-2018", "pickart-2015" ] }, { "q": "Does the thymosin beta-4 eye drop trial support injected TB-500?", "a": "No. It tested 0.1% thymosin beta-4 eye drops for dry eye in 72 adults, and neither primary endpoint beat placebo. It is a different formulation, route, and indication from injected TB-500, and products sold as TB-500 may not even be the full length peptide.", "source_ids": [ "sosne-2015", "goldstein-2012" ] }, { "q": "Can athletes use either one?", "a": "TB-500 is explicitly prohibited: thymosin beta-4 and TB-500 are named under S2 of the WADA Prohibited List. GHK-Cu is not named, but injected use of a non-approved substance may fall under S0, so tested athletes should avoid the injectable.", "source_ids": [ "wada-list-s2", "wada-list-s0" ] }, { "q": "Which is easier to get legally?", "a": "Topical GHK-Cu, which is sold over the counter as a cosmetic ingredient. Neither injectable has a lawful compounded path today: TB-500 was recommended for the 503A bulks list in July 2026 but awaits an FDA final rule, and injectable GHK-Cu is off Category 2 but not on the bulks list and was not reviewed. Research chemical vials of either are not lawful for human use.", "source_ids": [ "fda-cosmetics-vs-drugs", "fda-503a-bulks", "fda-pcac-2026" ] } ], "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": "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-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": "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-s2", "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": "wada-list-s0", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "TB-500 vs GHK-Cu: healing evidence and legal status", "description": "TB-500 vs GHK-Cu for healing and skin: animal and human evidence, WADA status, and why only topical GHK-Cu creams are lawful to buy in 2026." } }, { "slug": "teriparatide-vs-abaloparatide", "a": "teriparatide", "b": "abaloparatide", "title": "Teriparatide vs abaloparatide", "summary": "Both are FDA approved daily injections that build bone through the PTH1 receptor, and both sharply reduce vertebral fractures in randomized trials, so the choice depends on the patient. Abaloparatide caused less hypercalcemia than teriparatide (3.4% versus 6.4%) in the ACTIVE trial, which included an open label teriparatide arm, while teriparatide has the longer track record, a head-to-head win over risedronate, broader indications including glucocorticoid induced osteoporosis, and cheaper generic versions. Neither is available through compounding.", "verdict": { "winner": "depends", "rationale": "Both carry the top evidence grade and full FDA approval. In ACTIVE, new vertebral fractures were 0.58% with abaloparatide and 0.84% with teriparatide versus 4.22% with placebo, but the teriparatide arm was open label and the trial was not designed to prove one better than the other, while hypercalcemia was clearly less common with abaloparatide. Teriparatide has more indications (men, glucocorticoid induced osteoporosis) and generic pricing, and VERO showed it prevents more vertebral fractures than oral risedronate. Insurance coverage, calcium tolerance, and indication usually decide.", "source_ids": [ "active-2016", "neer-2001", "vero-2018", "fda-forteo-label", "fda-tymlos-label" ] }, "dimensions": [ { "name": "Molecule and mechanism", "a": "Recombinant human PTH (1-34); daily pulses activate the PTH1 receptor to favor bone formation over resorption.", "b": "Synthetic PTHrP (1-34) analog that preferentially binds the transient RG conformation of the PTH1 receptor, giving a shorter signal with less resorption and calcium rise.", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "name": "Pivotal placebo controlled result", "a": "Neer 2001 (1,637 women, median 21 months): new vertebral fractures 5% versus 14% placebo (relative risk 0.35); nonvertebral fragility fractures 3% versus 6%; lumbar spine BMD up 9%.", "b": "ACTIVE (2,463 women, 18 months): new vertebral fractures 0.58% versus 4.22% placebo (86% relative reduction); nonvertebral fractures hazard ratio 0.57; lumbar spine BMD up 11.2%.", "note": "The trials enrolled different populations over different periods, so absolute fracture rates are not directly comparable.", "source_ids": [ "neer-2001", "active-2016" ] }, { "name": "Active comparator evidence", "a": "VERO: new vertebral fractures 5.4% versus 12.0% with oral risedronate over 24 months (risk ratio 0.44) in severe osteoporosis.", "b": "ACTIVExtend: 18 months of abaloparatide followed by alendronate kept an 87% vertebral fracture reduction versus placebo followed by alendronate.", "source_ids": [ "vero-2018", "activextend-2017" ] }, { "name": "Hypercalcemia", "a": "6.4% in the open label teriparatide arm of ACTIVE; 11% versus 2% placebo in Neer 2001 (usually mild).", "b": "3.4% in ACTIVE, about half the teriparatide rate.", "source_ids": [ "active-2016", "neer-2001" ] }, { "name": "Other common side effects", "a": "Dizziness (9% versus 6%), leg cramps, nausea, headache, and orthostatic hypotension with the first doses.", "b": "Dizziness (10%), nausea (8%), headache (8%), palpitations (5%), and orthostatic hypotension within 4 hours of injection.", "source_ids": [ "neer-2001", "fda-tymlos-label" ] }, { "name": "FDA indications", "a": "Postmenopausal osteoporosis at high fracture risk, primary or hypogonadal osteoporosis in men, and glucocorticoid induced osteoporosis (Forteo, 2002; generic and 505(b)(2) products since).", "b": "Postmenopausal osteoporosis at high fracture risk (Tymlos, 2017) and osteoporosis in men (2022).", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "name": "Label dose and duration", "a": "20 mcg subcutaneously once daily in the thigh or abdomen; the label says use beyond 2 years in a lifetime should be considered only if fracture risk remains high (the osteosarcoma boxed warning was removed in 2020).", "b": "80 mcg subcutaneously once daily in the periumbilical abdomen; the label notes safety and efficacy were not evaluated beyond 2 years (the boxed warning was removed in 2021).", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "name": "Cost", "a": "Brand Forteo roughly 3,000 to 4,000 USD per month at list; generic and 505(b)(2) versions roughly 1,000 to 2,000 USD.", "b": "Roughly 2,000 to 3,000 USD per month at list; no generic; manufacturer copay program for commercially insured patients.", "note": "Both usually require prior authorization documenting high fracture risk.", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] } ], "head_to_head_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 an open label teriparatide arm, 18 months", "n": 2463, "population": "Postmenopausal women with osteoporosis", "outcome": "New vertebral fractures 0.58% with abaloparatide, 0.84% with open label teriparatide, and 4.22% with placebo; hypercalcemia 3.4% with abaloparatide versus 6.4% with teriparatide", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/27533157/" } ], "faqs": [ { "q": "Is abaloparatide better than teriparatide?", "a": "It has not been proven better at preventing fractures. In ACTIVE, vertebral fractures were 0.58% with abaloparatide and 0.84% with open label teriparatide, both far below placebo, but the trial was not designed to test superiority between the two. Abaloparatide did cause hypercalcemia about half as often.", "source_ids": [ "active-2016" ] }, { "q": "Which one is cheaper?", "a": "Teriparatide, because generic and 505(b)(2) versions are available at roughly 1,000 to 2,000 USD per month at list, compared with roughly 2,000 to 3,000 USD for abaloparatide, which has no generic. Actual cost depends mostly on insurance coverage and prior authorization.", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "q": "Can either be used in men or with steroid induced osteoporosis?", "a": "Both are approved for men with osteoporosis. Only teriparatide carries an FDA indication for glucocorticoid induced osteoporosis.", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "q": "Is there still a 2 year limit?", "a": "No. FDA removed the osteosarcoma boxed warning and the 2 year cumulative limit for teriparatide in 2020 and for abaloparatide in 2021, based on the absence of a human osteosarcoma signal. Longer use is now a clinical decision for patients who remain at high fracture risk.", "source_ids": [ "fda-forteo-label", "fda-tymlos-label" ] }, { "q": "What happens after treatment stops?", "a": "Bone gained on either drug is usually preserved by switching to an antiresorptive. ACTIVExtend showed that following abaloparatide with alendronate kept an 87% vertebral fracture reduction versus placebo followed by alendronate.", "source_ids": [ "activextend-2017", "fda-tymlos-label" ] }, { "q": "Are they allowed in sport?", "a": "Neither teriparatide nor abaloparatide is on the WADA Prohibited List, though athletes should confirm against the current list and any therapeutic use rules.", "source_ids": [ "wada-list" ] } ], "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": "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-forteo-label", "type": "fda", "title": "FDA prescribing information for Forteo (teriparatide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=forteo" }, { "id": "fda-tymlos-label", "type": "fda", "title": "FDA prescribing information for Tymlos (abaloparatide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=tymlos" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2 }, { "slug": "tesamorelin-vs-cjc-1295", "a": "tesamorelin", "b": "cjc-1295", "title": "Tesamorelin vs CJC-1295", "summary": "Both are growth hormone releasing hormone analogs, but only tesamorelin is an approved drug: as Egrifta it cut visceral fat by 15.4% relative to placebo at 26 weeks in phase 3 trials of 806 adults with HIV, and a 60 person trial in abdominal obesity without HIV found a similar visceral fat drop. CJC-1295 was engineered to bind albumin and last about a week, but its human data are two small hormone studies with no body composition or clinical endpoint. Development stopped, it has no lawful compounding basis, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "Tesamorelin wins on evidence and on legality. It has large randomized trials with a visceral fat endpoint, an FDA approval, and a lawful prescription path as Egrifta WR (as a biologic it cannot be compounded). CJC-1295 has raised GH and IGF-1 in healthy adults but was never tested for fat loss, body composition, or any clinical outcome, and its 503A nomination was withdrawn after FDA placed it on Category 2 in 2023. Tesamorelin's proven use is still limited to HIV associated abdominal fat; fat loss in other adults is off label.", "source_ids": [ "falutz-2010", "makimura-2012", "dailymed-egrifta-wr", "teichman-2006", "fda-503a-bulks", "fda-compounding-qa", "fda-biologics-transition" ] }, "dimensions": [ { "name": "Molecule", "a": "Full 44 amino acid GHRH analog with an N-terminal trans-3-hexenoic acid group that resists enzymatic cleavage; injected once daily.", "b": "29 amino acid GHRH(1-29) analog with four stabilizing substitutions and a drug affinity complex that binds circulating albumin, giving a half life of 5.8 to 8.1 days.", "note": "Products sold as CJC-1295 without DAC are a different molecule (modified GRF 1-29) with no published human trials under that name.", "source_ids": [ "dailymed-egrifta-wr", "teichman-2006" ] }, { "name": "Best human evidence", "a": "Pooled phase 3 trials in 806 adults with HIV: visceral fat minus 24 versus plus 2 cm2 at 26 weeks (treatment effect minus 15.4%), triglycerides minus 37 versus plus 6 mg/dL.", "b": "Two randomized, placebo controlled ascending dose trials 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.", "source_ids": [ "falutz-2010", "teichman-2006" ] }, { "name": "Body composition outside HIV", "a": "60 abdominally obese adults with reduced GH secretion, 12 months: visceral fat treatment effect minus 35 cm2 versus placebo, with lower triglycerides and C-reactive protein and no change in glucose or HbA1c.", "b": "No trial has measured body composition, fat loss, strength, or sleep. The only other human study found trough GH up 7.5 fold and IGF-1 up 45% a week after one dose, with GH pulses preserved.", "source_ids": [ "makimura-2012", "ionescu-2006", "teichman-2006" ] }, { "name": "Liver fat", "a": "HIV with fatty liver (61 adults, 12 months): hepatic fat fraction down an absolute 4.1%; 35% versus 4% on placebo reached normal liver fat.", "b": "No liver fat or metabolic outcome trial.", "source_ids": [ "stanley-2019", "teichman-2006" ] }, { "name": "FDA status", "a": "FDA approved as Egrifta (2010), Egrifta SV (2019), and Egrifta WR to reduce excess abdominal fat in adults with HIV and lipodystrophy.", "b": "Never approved anywhere; development for HIV lipodystrophy and GH deficiency was discontinued.", "source_ids": [ "dailymed-egrifta-wr", "teichman-2006" ] }, { "name": "Compounding status", "a": "Biologic since March 2020 (BLA 022505), so it is not eligible for 503A or 503B compounding; Egrifta WR by prescription is the only lawful product.", "b": "Placed on the 503A Category 2 list in September 2023, then listed as a withdrawn nomination; not reviewed at the July 2026 advisory committee meeting. No lawful basis for compounding.", "source_ids": [ "fda-compounding-qa", "fda-503a-bulks", "fda-pcac-2026" ] }, { "name": "Dosing", "a": "Egrifta WR label: 1.28 mg injected under the skin of the abdomen once daily. Egrifta WR and the earlier Egrifta SV are not interchangeable.", "b": "No dose established for any use. Trials tested only single and short repeated doses over 28 to 49 days to measure hormone levels.", "source_ids": [ "dailymed-egrifta-wr", "teichman-2006" ] }, { "name": "Side effects", "a": "Arthralgia (about 13%), injection site reactions, peripheral edema, myalgia, paresthesia; the label advises monitoring glucose and IGF-1.", "b": "Injection site reactions, flushing, and headache in the small trials; FDA cited increased heart rate and a systemic vasodilatory reaction in its Category 2 review. No long term safety data.", "source_ids": [ "dailymed-egrifta-wr", "teichman-2006", "fda-503a-bulks" ] }, { "name": "Typical cost", "a": "Egrifta WR retail cash price about 10,709 USD per 28 day kit at a listing checked 2026-09-22; plans cover it for the HIV indication, usually with prior authorization.", "b": "Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.", "note": "Prices at the verification date change often.", "source_ids": [ "price-listing-egrifta-wr", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is CJC-1295 a longer acting version of tesamorelin?", "a": "No. Both act on the GHRH receptor, but they are different molecules. Tesamorelin is the full 44 amino acid hormone with a protective chemical group and is injected daily. CJC-1295 is a 29 amino acid fragment linked to albumin so one injection lasts about a week. Only tesamorelin has been tested for a clinical outcome.", "source_ids": [ "dailymed-egrifta-wr", "teichman-2006" ] }, { "q": "Which is better for belly fat?", "a": "Tesamorelin is the only one with trial evidence: it reduced visceral fat by 15.4% relative to placebo in adults with HIV, and by 35 cm2 versus placebo over 12 months in abdominally obese adults with low GH. No trial has measured fat loss with CJC-1295.", "source_ids": [ "falutz-2010", "makimura-2012", "teichman-2006" ] }, { "q": "Can either be prescribed legally?", "a": "Neither can be compounded. Tesamorelin is available by prescription as Egrifta WR, but it became a biologic in 2020 and biologics are not eligible for 503A compounding. CJC-1295 has no lawful path: it was placed on Category 2 in 2023, its nomination was withdrawn, and it is not on the bulks list.", "source_ids": [ "dailymed-egrifta-wr", "fda-compounding-qa", "fda-503a-bulks", "fda-biologics-transition" ] }, { "q": "Does either help build muscle?", "a": "Neither is proven to. Tesamorelin's trials measured visceral fat, liver fat, and blood lipids, and muscle gain is not an approved use. CJC-1295's trials measured only GH and IGF-1 levels in healthy adults.", "source_ids": [ "falutz-2010", "makimura-2012", "teichman-2006" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are growth hormone releasing hormone analogs prohibited at all times under WADA section S2.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "dailymed-egrifta-wr", "type": "fda", "title": "FDA prescribing information for Egrifta WR (tesamorelin) for injection, via DailyMed (Indications, Dosage and Administration, Adverse Reactions, and How Supplied sections)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75" }, { "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": "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (growth hormone releasing hormone and its analogues, including tesamorelin and CJC-1295)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 1 }, { "slug": "tesamorelin-vs-ipamorelin", "a": "tesamorelin", "b": "ipamorelin", "title": "Tesamorelin vs ipamorelin", "summary": "Tesamorelin is an FDA approved growth hormone releasing hormone analog (Egrifta WR and Egrifta SV) that reduced visceral fat by 15.4% relative to placebo in phase 3 trials of 806 people with HIV. Ipamorelin is an unapproved ghrelin receptor agonist: one small human pharmacology study showed a single IV infusion releases growth hormone in healthy men, its only randomized trial (postoperative ileus) was negative, no human trial measured body composition or muscle, and it has no lawful basis for compounding. Tesamorelin wins clearly, though its proven use is limited to HIV associated abdominal fat, and both are prohibited in sport.", "verdict": { "winner": "a", "rationale": "Tesamorelin has large randomized trials with a body composition endpoint, an FDA approval, and a lawful prescription path as Egrifta WR (as a biologic it cannot be compounded). Ipamorelin is graded animal_only for its marketed uses, was placed on the 503A Category 2 list in 2023, and is now a withdrawn nomination. Tesamorelin's off label use for fat loss in people without HIV is still untested.", "source_ids": [ "falutz-2010", "egrifta-label", "beck-2014", "raun-1998", "fda-503a-bulks", "fda-biologics-transition", "gobburu-1999" ] }, "dimensions": [ { "name": "Mechanism", "a": "Stabilized 44 amino acid GHRH analog acting on the pituitary GHRH receptor; feedback loops remain intact.", "b": "Pentapeptide ghrelin receptor (GHS-R1a) agonist; GH release through a separate pathway, also stimulates gut motility.", "source_ids": [ "egrifta-label", "raun-1998", "venkova-2009" ] }, { "name": "Evidence grade", "a": "Human RCT: pooled phase 3 trials (806 adults with HIV) and a 61 person liver fat RCT.", "b": "Animal only for GH related uses; the one human RCT (117 adults) tested intravenous ipamorelin for postoperative ileus.", "source_ids": [ "falutz-2010", "stanley-2019", "raun-1998", "beck-2014" ] }, { "name": "Key human results", "a": "Visceral fat minus 24 versus plus 2 cm2 at 26 weeks (treatment effect minus 15.4%); liver fat fraction down an absolute 4.1% in HIV associated fatty liver.", "b": "Time to first tolerated meal 25.3 versus 32.6 hours on placebo (p = 0.15); no significant difference on any efficacy endpoint.", "source_ids": [ "falutz-2010", "stanley-2019", "beck-2014" ] }, { "name": "FDA status", "a": "FDA approved as Egrifta (2010), Egrifta SV (2019), and Egrifta WR (2025) to reduce excess abdominal fat in adults with HIV associated lipodystrophy.", "b": "Never approved anywhere; development stopped after the ileus trial.", "source_ids": [ "dailymed-egrifta-wr", "beck-2014" ] }, { "name": "Compounding status", "a": "Biologic since March 2020 (BLA 022505), so it is not eligible for 503A or 503B compounding; Egrifta WR by prescription is the only lawful product.", "b": "503A Category 2 in September 2023, nominations withdrawn in 2024; ipamorelin acetate remains in 503B Category 2. No lawful basis for compounding.", "source_ids": [ "fda-compounding-qa", "fda-503a-bulks" ] }, { "name": "Dosing", "a": "FDA label: Egrifta WR 1.28 mg or Egrifta SV 1.4 mg injected under the skin of the abdomen once daily (the formulations are not substitutable); the phase 3 trials used 2 mg daily of the original Egrifta. Effect fades after stopping.", "b": "Not established for GH use; the human trial used 0.03 mg/kg intravenously twice daily for up to 7 days.", "source_ids": [ "beck-2014", "dailymed-egrifta-wr", "dailymed-egrifta-sv" ] }, { "name": "Side effects", "a": "Arthralgia (about 13%), injection site reactions, edema, myalgia, paresthesia; glucose intolerance in some patients, so the label advises monitoring glucose and IGF-1.", "b": "No safety signal versus placebo over 7 days in the ileus trial; FDA cited immunogenicity risk from aggregation and impurities; long term effects untested.", "source_ids": [ "egrifta-label", "beck-2014", "fda-503a-bulks" ] }, { "name": "Typical cost", "a": "Egrifta WR has no published list price; one retail cash listing put a 28 day kit at about 10,709 USD (checked 2026-09-22). Compounded tesamorelin has no lawful price because tesamorelin is a biologic; dated prices are on the tesamorelin cost page.", "b": "Not available through licensed channels; research chemical listings are not lawful for human use.", "note": "Prices at the verification date change often.", "source_ids": [ "fda-503a-bulks", "price-listing-egrifta-wr", "dailymed-egrifta-wr", "fda-biologics-transition" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for reducing belly fat?", "a": "Tesamorelin is the only one with trial evidence: it reduced visceral fat by 15.4% relative to placebo over 26 weeks in people with HIV. Ipamorelin has never been tested for body composition in humans.", "source_ids": [ "falutz-2010", "beck-2014" ] }, { "q": "Do they work the same way?", "a": "No. Tesamorelin mimics growth hormone releasing hormone at the GHRH receptor, while ipamorelin mimics ghrelin at the growth hormone secretagogue receptor. Both end in pituitary GH release through different signals.", "source_ids": [ "egrifta-label", "raun-1998" ] }, { "q": "Can I get either one legally?", "a": "Tesamorelin yes, but only as Egrifta WR or Egrifta SV by prescription; it became a biologic in 2020, and biologics cannot be compounded under 503A. Ipamorelin has no lawful compounding basis after its Category 2 listing and withdrawn nomination.", "source_ids": [ "egrifta-label", "fda-compounding-qa", "fda-503a-bulks", "dailymed-egrifta-wr", "fda-biologics-transition" ] }, { "q": "Does tesamorelin raise blood sugar?", "a": "In the pooled phase 3 trials glucose parameters did not differ meaningfully from placebo, and the liver fat trial found no difference in glucose or HbA1c, but the label notes glucose intolerance in some patients and advises monitoring.", "source_ids": [ "falutz-2010", "stanley-2019", "egrifta-label" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are prohibited at all times under WADA section S2.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S2 (GHRH analogues and growth hormone secretagogues)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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": "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": "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 }, { "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Tesamorelin vs ipamorelin: evidence, cost, and legality", "description": "Tesamorelin vs ipamorelin: an FDA approved GHRH analog against an unapproved ghrelin mimetic, compared on evidence, safety, and legality.", "h1": "Tesamorelin vs ipamorelin (ipamorelin vs tesamorelin)" } }, { "slug": "tesamorelin-vs-mk-677", "a": "tesamorelin", "b": "mk-677", "title": "Tesamorelin vs MK-677 (ibutamoren)", "summary": "Tesamorelin is the clear choice: it is an FDA approved GHRH analog with phase 3 trials showing a 15.4% reduction in visceral fat in HIV lipodystrophy and a 37% relative reduction in liver fat in a later randomized trial, and it can be prescribed lawfully as Egrifta WR. MK-677 is an oral ghrelin mimetic with real randomized trials of its own, but those trials showed about 1.1 kg of lean mass gain without strength or function benefit, higher fasting glucose, and a hip fracture trial stopped for a heart failure signal, which is why FDA placed it in both 503A and 503B Category 2. Both are prohibited by WADA at all times.", "verdict": { "winner": "a", "rationale": "Both have a human RCT evidence grade, but tesamorelin's trials produced an approvable outcome (visceral fat reduction in 806 patients) and an FDA label, while MK-677's largest trial (2 years, 65 older adults) found lean mass gain with no functional benefit and worsening glucose, and a later trial was terminated for a possible congestive heart failure signal. On regulation the gap is wider: tesamorelin is FDA approved and available by prescription as Egrifta WR, MK-677 is unapproved and sits in Category 2 for both 503A and 503B, leaving no lawful access path.", "source_ids": [ "falutz-2010", "stanley-2019", "egrifta-label", "nass-2008", "adunsky-2011", "fda-category-2", "wada-list" ] }, "dimensions": [ { "name": "Mechanism", "a": "Stabilized 44 amino acid GHRH analog. Binds pituitary GHRH receptors to increase pulsatile GH release with feedback loops intact; the hexenoyl modification resists dipeptidyl peptidase cleavage.", "b": "Oral non peptide agonist of the ghrelin receptor (GHS-R1a). Amplifies GH pulse amplitude without changing frequency, raises IGF-1 for a full day after one dose, and as a ghrelin mimetic increases hunger.", "source_ids": [ "egrifta-label", "chapman-1996" ] }, { "name": "Trial evidence", "a": "Two multicenter double blind placebo controlled phase 3 trials pooled (806 patients, 26 weeks plus extension) and a 12 month NIH funded randomized trial in 61 patients with HIV associated fatty liver.", "b": "A 2 year randomized trial in 65 healthy older adults, an 8 week trial in 24 obese men, a 12 month trial in 563 Alzheimer patients showing no benefit, and a phase 2b hip fracture trial terminated early.", "source_ids": [ "falutz-2010", "stanley-2019", "nass-2008", "svensson-1998", "sevigny-2008", "adunsky-2011" ] }, { "name": "Effect on fat and lean mass", "a": "Visceral adipose tissue fell 24 cm2 versus a 2 cm2 rise on placebo at 26 weeks (treatment effect minus 15.4%), with no change in abdominal subcutaneous fat; hepatic fat fraction fell an absolute 4.1 points over 12 months. Fat returns after stopping.", "b": "Fat free mass rose about 1.1 kg over 2 years and about 3 kg over 8 weeks in obese men, with increased energy expenditure but no significant fat loss and no improvement in strength or function.", "source_ids": [ "falutz-2010", "stanley-2019", "nass-2008", "svensson-1998" ] }, { "name": "Glucose effects", "a": "Glucose parameters did not differ meaningfully from placebo in the pooled phase 3 trials or the fatty liver trial, but the label warns of glucose intolerance and new diabetes in some patients and advises monitoring.", "b": "Fasting glucose rose about 0.3 mmol/L and insulin sensitivity fell over 2 years; higher glucose is a consistent finding across trials.", "source_ids": [ "falutz-2010", "egrifta-label", "nass-2008" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection into the abdomen once daily: Egrifta WR 1.28 mg or Egrifta SV 1.4 mg on the FDA label; the original Egrifta used 2 mg.", "b": "Oral capsule or tablet once daily; trials used 25 mg.", "source_ids": [ "nass-2008", "dailymed-egrifta-wr", "dailymed-egrifta-sv" ] }, { "name": "Safety signals", "a": "Arthralgia (about 13%), injection site reactions, peripheral edema, paresthesia, hypersensitivity; label requires IGF-1 monitoring and lists contraindications for active malignancy, pituitary disruption, and pregnancy.", "b": "Increased appetite, edema, muscle and joint pain, transient cortisol and prolactin rise, and a possible congestive heart failure signal that halted the hip fracture trial and is FDA's stated Category 2 rationale.", "source_ids": [ "egrifta-label", "nass-2008", "adunsky-2011", "fda-category-2" ] }, { "name": "Regulatory status", "a": "FDA approved as Egrifta on November 10, 2010 for excess abdominal fat in HIV lipodystrophy; Egrifta SV approved 2019 and Egrifta WR in 2025. Egrifta became a biologic on March 23, 2020, and biologics are not eligible for 503A or 503B compounding, so Egrifta WR by prescription is the only lawful product; use for fat loss without HIV is off-label.", "b": "Never approved. Placed in 503B Category 2 on December 29, 2022 and 503A Category 2 on September 29, 2023; still in both as of April 22, 2026, so no pharmacy or outsourcing facility can lawfully compound it, and FDA has warned that supplements containing it are misbranded.", "source_ids": [ "egrifta-label", "fda-compounding-qa", "fda-category-2", "dailymed-egrifta-wr", "fda-biologics-transition" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S2, which names tesamorelin among GHRH analogues.", "b": "Prohibited at all times under section S2, which names ibutamoren among GH secretagogues.", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "Egrifta WR has no published list price; one retail cash listing put a 28 day kit at about 10,709 USD (checked 2026-09-22). Compounded tesamorelin has no lawful price because tesamorelin is a biologic; dated prices are on the tesamorelin cost page.", "b": "No licensed channel. Products sold as research chemicals or supplements are not lawful for human use and are not verified for identity or purity.", "source_ids": [ "fda-category-2", "price-listing-egrifta-wr", "dailymed-egrifta-wr", "fda-biologics-transition" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for losing belly fat, tesamorelin or MK-677?", "a": "Tesamorelin, and it is not close. It reduced visceral fat by 15.4% relative to placebo in 806 HIV patients with lipodystrophy and reduced liver fat by 37% in a 12 month trial. MK-677 increased lean mass and energy expenditure but produced no significant fat loss in its trials. Note that tesamorelin's evidence is in HIV lipodystrophy; its use for fat loss in people without HIV is off-label and untested.", "source_ids": [ "falutz-2010", "stanley-2019", "svensson-1998", "nass-2008" ] }, { "q": "Is MK-677 safer because it is oral?", "a": "No. The route is more convenient, but the trials showed higher fasting glucose, reduced insulin sensitivity, edema, and increased appetite, and a hip fracture trial was stopped early for a possible congestive heart failure signal. That signal is the reason FDA placed ibutamoren in Category 2 for both 503A and 503B compounding.", "source_ids": [ "nass-2008", "adunsky-2011", "fda-category-2" ] }, { "q": "Can either be prescribed in the United States?", "a": "Tesamorelin can, by prescription: Egrifta WR and Egrifta SV are FDA approved for HIV lipodystrophy. Compounded tesamorelin is not lawful, because tesamorelin became a biologic in 2020 and biologics cannot be compounded. MK-677 cannot: it is unapproved, in Category 2 for both compounding pathways, and may not lawfully be sold as a supplement.", "source_ids": [ "egrifta-label", "fda-compounding-qa", "fda-category-2", "dailymed-egrifta-wr", "fda-biologics-transition" ] }, { "q": "Do both raise IGF-1?", "a": "Yes, by different routes. Tesamorelin raised IGF-1 by about 108 ng/mL in the phase 3 trials and the label calls for monitoring and discontinuation if persistently elevated. MK-677 raised IGF-1 by roughly 50 to 60% into the young adult range in older adults. Both carry the theoretical tumor growth concern that comes with sustained IGF-1 elevation.", "source_ids": [ "falutz-2010", "egrifta-label", "nass-2008", "chapman-1996" ] }, { "q": "Are they allowed in sport?", "a": "No. Both are prohibited at all times under WADA section S2: tesamorelin as a GHRH analogue and ibutamoren as a growth hormone secretagogue.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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-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 S2 (GHRH analogues including tesamorelin; GH secretagogues including ibutamoren)", "url": "https://www.wada-ama.org/en/prohibited-list", "year": 2026 }, { "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": "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Tesamorelin vs MK-677: evidence, cost, and legality", "description": "Tesamorelin vs MK-677 (ibutamoren): trial evidence on belly fat and lean mass, glucose effects, safety signals, and US legal status." } }, { "slug": "tesamorelin-vs-retatrutide", "a": "tesamorelin", "b": "retatrutide", "title": "Tesamorelin vs retatrutide", "summary": "These are different drugs for different goals. Tesamorelin is an FDA approved growth hormone releasing hormone analog that targets visceral fat: it cut belly fat inside the abdomen by 15.4% relative to placebo in adults with HIV without changing fat under the skin. Retatrutide is an investigational GIP, GLP-1, and glucagon receptor agonist that produced 24.2% total weight loss at 48 weeks in a phase 2 obesity trial. Tesamorelin can be prescribed today; retatrutide is available only inside clinical trials. There is no head-to-head trial.", "verdict": { "winner": "depends", "rationale": "On access and regulatory status tesamorelin wins: it is approved and available by prescription as Egrifta WR, while retatrutide is not approved anywhere and cannot be compounded. On the size of the effect retatrutide's trial results are far larger, for both body weight and liver fat, but they come from phase 2 and early phase 3 trials with no cardiovascular outcomes data. For obesity, the lawful comparison for retatrutide is an approved GLP-1 medicine, not tesamorelin, whose only approved use is HIV associated abdominal fat.", "source_ids": [ "falutz-2010", "dailymed-egrifta-wr", "fda-compounding-qa", "retatrutide-phase2-obesity", "sanyal-2024", "triumph-design", "fda-glp1-compounding" ] }, "dimensions": [ { "name": "Mechanism", "a": "Stabilized 44 amino acid GHRH analog: raises the body's own growth hormone and IGF-1, which mobilizes visceral fat.", "b": "Single peptide that activates the GIP, GLP-1, and glucagon receptors: lowers appetite, slows gastric emptying, and raises energy expenditure.", "source_ids": [ "dailymed-egrifta-wr", "retatrutide-phase2-obesity" ] }, { "name": "What the trials measured", "a": "Visceral fat by CT scan. Pooled phase 3 trials in 806 adults with HIV: minus 24 versus plus 2 cm2 at 26 weeks (treatment effect minus 15.4%), with no change in abdominal fat under the skin.", "b": "Total body weight. Phase 2 trial in 338 adults with obesity: minus 8.7%, 17.1%, 22.8%, and 24.2% at 1, 4, 8, and 12 mg versus minus 2.1% on placebo at 48 weeks.", "note": "Different outcomes, populations, and trial lengths. No direct comparison exists.", "source_ids": [ "falutz-2010", "retatrutide-phase2-obesity" ] }, { "name": "People without HIV", "a": "One 12 month trial in 60 abdominally obese adults with reduced GH secretion: visceral fat treatment effect minus 35 cm2, with lower triglycerides and no change in glucose or HbA1c.", "b": "Trials enrolled adults with obesity or type 2 diabetes; the phase 3 TRANSCEND-T2D-1 trial (537 adults, 40 weeks) improved glycemic control and weight versus placebo.", "source_ids": [ "makimura-2012", "transcend-t2d-1" ] }, { "name": "Liver fat", "a": "HIV with fatty liver (61 adults, 12 months): hepatic fat fraction down an absolute 4.1%; 35% versus 4% on placebo reached normal liver fat.", "b": "Substudy of 98 adults with fatty liver: relative liver fat change at 24 weeks of minus 82.4% at 12 mg versus plus 0.3% on placebo; 86% versus 0% reached normal liver fat.", "source_ids": [ "stanley-2019", "sanyal-2024" ] }, { "name": "FDA status", "a": "FDA approved: Egrifta (2010), Egrifta SV (2019), and Egrifta WR, for excess abdominal fat in adults with HIV and lipodystrophy.", "b": "Not approved by FDA or any other regulator. Phase 3 obesity trials (TRIUMPH) are the confirmatory step.", "source_ids": [ "dailymed-egrifta-wr", "triumph-design" ] }, { "name": "Compounding status", "a": "Biologic since March 2020 (BLA 022505), so it is not eligible for 503A or 503B compounding; Egrifta WR by prescription is the only lawful product. Fat loss in people without HIV is off label.", "b": "Not a component of an approved drug and not on the 503A bulks list, so it cannot lawfully be compounded. The only lawful access is a registered clinical trial.", "source_ids": [ "fda-compounding-qa", "fda-503a-bulks", "fda-glp1-compounding" ] }, { "name": "Dosing", "a": "Egrifta WR label: 1.28 mg injected under the skin of the abdomen once daily; the effect fades after stopping.", "b": "No approved dose. Weekly injections have been given only inside clinical trials.", "source_ids": [ "dailymed-egrifta-wr", "falutz-2010", "triumph-design" ] }, { "name": "Side effects", "a": "Arthralgia (about 13%), injection site reactions, peripheral edema, myalgia, paresthesia; the label advises monitoring glucose and IGF-1.", "b": "Dose related nausea, diarrhea, vomiting, and constipation, mostly mild to moderate, and a dose dependent heart rate rise that peaked at 24 weeks; long term safety not established.", "source_ids": [ "dailymed-egrifta-wr", "retatrutide-phase2-obesity" ] }, { "name": "WADA status", "a": "Prohibited at all times under section S2 (GHRH analogues).", "b": "Prohibited at all times under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Typical cost", "a": "Egrifta WR retail cash price about 10,709 USD per 28 day kit at a listing checked 2026-09-22; plans cover it for the HIV indication, usually with prior authorization.", "b": "No lawful price. Trial participants receive it at no cost; products sold online as retatrutide are unapproved and unverified.", "note": "Prices at the verification date change often.", "source_ids": [ "price-listing-egrifta-wr", "fda-glp1-compounding" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which is better for belly fat?", "a": "They work differently. Tesamorelin selectively reduces visceral fat inside the abdomen and was approved for that in adults with HIV. Retatrutide reduces total body weight, but it was not tested as a visceral fat drug and is not approved. No trial has compared them.", "source_ids": [ "falutz-2010", "makimura-2012", "retatrutide-phase2-obesity" ] }, { "q": "Does tesamorelin cause weight loss like retatrutide?", "a": "No. Tesamorelin's trials measured visceral fat, not body weight, and it did not change fat under the skin. Retatrutide's phase 2 trial measured body weight and found a mean 24.2% loss at the top dose over 48 weeks.", "source_ids": [ "falutz-2010", "retatrutide-phase2-obesity" ] }, { "q": "Which one can I get legally?", "a": "Tesamorelin, by prescription as Egrifta WR; as a biologic it cannot be compounded. Retatrutide is not approved and cannot be compounded, so the only lawful access is enrolling in a registered clinical trial.", "source_ids": [ "dailymed-egrifta-wr", "fda-compounding-qa", "fda-503a-bulks", "fda-glp1-compounding", "fda-biologics-transition" ] }, { "q": "Do both lower liver fat?", "a": "Both did in trials of people with fatty liver. Tesamorelin lowered hepatic fat fraction by an absolute 4.1% over 12 months in adults with HIV. Retatrutide lowered liver fat by 82.4% relative to baseline at 24 weeks on the top dose in a 98 person substudy.", "source_ids": [ "stanley-2019", "sanyal-2024" ] }, { "q": "Are they allowed in sport?", "a": "No. Tesamorelin is prohibited under WADA section S2 and retatrutide under section S0.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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": "sanyal-2024", "type": "pubmed", "title": "Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med 2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38858523/", "pmid": "38858523", "year": 2024 }, { "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": "dailymed-egrifta-wr", "type": "fda", "title": "FDA prescribing information for Egrifta WR (tesamorelin) for injection, via DailyMed (Indications, Dosage and Administration, Adverse Reactions, and How Supplied sections)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75" }, { "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": "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" }, { "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" }, { "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": "wada-list", "type": "wada", "title": "WADA Prohibited List, sections S0 (non-approved substances, including retatrutide) and S2 (GHRH analogues, including tesamorelin)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 1 }, { "slug": "tesofensine-vs-semaglutide", "a": "tesofensine", "b": "semaglutide", "title": "Tesofensine vs semaglutide", "summary": "Semaglutide is the better choice: it is FDA approved, its weight loss is proven in large phase 3 trials (14.9% versus 2.4% on placebo at 68 weeks in STEP 1), and it reduced major cardiovascular events by 20% in SELECT. Tesofensine, an oral triple reuptake inhibitor rather than a peptide, produced about 9% to 11% placebo adjusted weight loss in one 24 week phase 2 trial of 203 people, but it raised heart rate and blood pressure and has no US approval or lawful source. The appeal of tesofensine is that it is a pill; semaglutide is also available as an oral tablet.", "verdict": { "winner": "b", "rationale": "Semaglutide wins on evidence (multiple phase 3 trials with weight and cardiovascular outcomes versus a single 24 week phase 2 trial), on safety direction (it lowers cardiovascular events, while tesofensine raised heart rate by about 7 beats per minute and blood pressure at the top dose), and on regulatory status (FDA approved versus never nominated for compounding and no US marketing authorization). Tesofensine's phase 2 weight loss was substantial, but without phase 3 data or a lawful US source it is not a comparable option.", "source_ids": [ "step-1", "select", "astrup-2008", "doggrell-2009", "fda-wegovy-label", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Drug type", "a": "Oral small molecule (not a peptide) that inhibits serotonin, noradrenaline, and dopamine reuptake.", "b": "31 amino acid GLP-1 receptor agonist peptide, acylated for once weekly dosing.", "source_ids": [ "astrup-2008", "fda-wegovy-label" ] }, { "name": "Evidence grade", "a": "Human RCT, but one phase 2 trial in obesity (203 adults, 24 weeks); no published phase 3 program.", "b": "Human RCT, many phase 3 trials, including STEP 1 (1,961 adults, 68 weeks) and SELECT (17,604 adults).", "source_ids": [ "astrup-2008", "step-1", "select" ] }, { "name": "Weight loss", "a": "6.7, 11.3, and 12.8 kg at 0.25, 0.5, and 1.0 mg daily versus 2.2 kg on placebo with diet at 24 weeks (placebo adjusted 4.5%, 9.2%, and 10.6%).", "b": "14.9% versus 2.4% with placebo at 68 weeks with 2.4 mg weekly.", "note": "Cross-trial comparisons are unreliable because the trials differed in length, diet intensity, and population. No direct comparison exists.", "source_ids": [ "astrup-2008", "step-1" ] }, { "name": "Cardiovascular effects", "a": "Heart rate rose about 7.4 beats per minute at 1.0 mg and blood pressure rose at that dose; long term cardiovascular safety not established.", "b": "20% relative reduction in major adverse cardiovascular events in SELECT (hazard ratio 0.80).", "source_ids": [ "astrup-2008", "doggrell-2009", "select" ] }, { "name": "Common side effects", "a": "Dry mouth, nausea, constipation, diarrhea, and insomnia; mood changes possible given its dopaminergic and serotonergic action.", "b": "Nausea (44% versus 16% placebo), diarrhea, vomiting, and constipation, highest during dose escalation; gallbladder disease and rare pancreatitis.", "source_ids": [ "astrup-2008", "step-1", "fda-wegovy-label" ] }, { "name": "Key interactions", "a": "Theoretical serotonin syndrome and hypertensive risk with MAO inhibitors and serotonergic antidepressants; additive effects with stimulants.", "b": "Hypoglycemia with insulin or sulfonylureas; delayed gastric emptying can change absorption of oral drugs.", "source_ids": [ "doggrell-2009", "fda-wegovy-label" ] }, { "name": "Regulatory status", "a": "Not FDA approved, no 503A nomination, and not on any compounding list; no lawful US source outside a trial.", "b": "FDA approved as Wegovy, Ozempic, and Rybelsus; shortage based compounding ended in 2025.", "source_ids": [ "fda-503a-bulks", "fda-category-2", "fda-wegovy-label", "fda-glp1-compounding" ] }, { "name": "WADA status", "a": "Unclear; not named, but could fall under S0 non-approved substances or S6 stimulants.", "b": "Not prohibited.", "source_ids": [ "wada-list" ] }, { "name": "Route and frequency", "a": "Oral, once daily (trial doses 0.25 to 1.0 mg, with 0.5 mg the best balance).", "b": "Subcutaneous injection once weekly, titrated to 2.4 mg (Wegovy), or oral tablet once daily.", "source_ids": [ "astrup-2008", "fda-wegovy-label" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is tesofensine as effective as semaglutide?", "a": "It has not been compared directly. Tesofensine produced about 9% to 11% placebo adjusted weight loss at 24 weeks in one phase 2 trial, while semaglutide produced 14.9% versus 2.4% on placebo at 68 weeks in phase 3. The trials differed too much to rank them precisely, and semaglutide's evidence base is far larger.", "source_ids": [ "astrup-2008", "step-1" ] }, { "q": "Is tesofensine a peptide?", "a": "No. Tesofensine is an oral small molecule that blocks the reuptake of serotonin, noradrenaline, and dopamine. It is often marketed alongside peptides but works through brain neurotransmitters rather than hormone receptors.", "source_ids": [ "astrup-2008" ] }, { "q": "Is tesofensine safe for the heart?", "a": "That has not been established. In the phase 2 trial the highest dose raised heart rate by about 7 beats per minute and increased blood pressure, and reviewers flagged cardiovascular safety as the key question for later trials. Semaglutide, by contrast, lowered major cardiovascular events in SELECT.", "source_ids": [ "astrup-2008", "doggrell-2009", "select" ] }, { "q": "Can I get tesofensine legally in the United States?", "a": "No. It has no FDA approval, no compounding nomination, and is not on any FDA compounding list, so there is no lawful US source outside a clinical trial. Semaglutide is available by prescription.", "source_ids": [ "fda-503a-bulks", "fda-category-2" ] }, { "q": "Is there a pill alternative to semaglutide injections?", "a": "Yes, semaglutide itself comes as a once daily oral tablet (Rybelsus for type 2 diabetes, and an oral Wegovy formulation), so choosing tesofensine for the pill form is not necessary.", "source_ids": [ "fda-wegovy-label" ] } ], "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": "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": "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": "fda-wegovy-label", "type": "fda", "title": "FDA prescribing information for Wegovy (semaglutide) injection, via DailyMed", "url": "https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=wegovy" }, { "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" }, { "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" }, { "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" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "thymosin-alpha-1-vs-tb-500", "a": "thymosin-alpha-1", "b": "tb-500", "title": "Thymosin alpha-1 vs TB-500 (thymosin beta-4)", "summary": "Despite the shared name, these are unrelated peptides with different jobs: thymosin alpha-1 is an immune modulator with randomized trials in hepatitis B and sepsis and approval abroad as Zadaxin, while TB-500 is a version or fragment of thymosin beta-4, an actin binding repair peptide with strong animal wound and heart data and no human trial of the injectable. Thymosin alpha-1 has much better evidence, but TB-500 currently has the clearer US path, having received a favorable Pharmacy Compounding Advisory Committee vote in July 2026. TB-500 is prohibited in sport; thymosin alpha-1 is not named on the WADA list.", "verdict": { "winner": "a", "rationale": "Thymosin alpha-1 wins on evidence grade (human RCT versus animal only) and on regulatory standing internationally, as an approved drug in more than 30 countries with a benign safety record across decades of trials. TB-500's only human randomized data are for a 0.1% eye drop in dry eye, where both primary endpoints missed, and the identity of injectable products sold as TB-500 is not verified. The US access picture runs the other way: thymosin alpha-1's compounding nomination was withdrawn, while TB-500 is awaiting a final FDA rule after the July 2026 PCAC recommendation.", "source_ids": [ "chien-1998", "wu-2013", "camerini-2015", "sosne-2015", "malinda-1999", "fda-category-2", "fda-pcac-2026" ] }, "dimensions": [ { "name": "What it is", "a": "A 28 amino acid N-acetylated thymic peptide (thymalfasin).", "b": "Synthetic thymosin beta-4 (43 amino acids) or its 7 amino acid actin binding fragment LKKTETQ, depending on the product.", "note": "The two are not related in structure or function; both were first isolated from thymus extracts, which explains the shared name.", "source_ids": [ "dominari-2020", "goldstein-2012" ] }, { "name": "Mechanism", "a": "Immune modulation through TLR2 and TLR9 on dendritic cells: more IL-2 and interferon, stronger natural killer and CD8 activity, fewer exhausted T cells.", "b": "Sequesters G-actin to regulate cell migration; in animals promotes keratinocyte, endothelial, and cardiomyocyte migration and activates Akt through a PINCH and ILK complex.", "source_ids": [ "dominari-2020", "liu-2020", "bock-marquette-2004", "goldstein-2012" ] }, { "name": "Evidence grade", "a": "Human RCT: hepatitis B trial (98 patients, 40.6% versus 9.4% virological response) and sepsis trial (361 patients, 26.0% versus 35.0% 28 day mortality, p = 0.062).", "b": "Animal only: rat wound reepithelialization up 42% at day 4 and 61% at day 7; improved cardiac function after infarction in mice. No human trial of the injectable.", "source_ids": [ "chien-1998", "wu-2013", "malinda-1999", "bock-marquette-2004" ] }, { "name": "Main uses", "a": "Chronic viral hepatitis, sepsis, vaccine adjuvant in immunocompromised patients, and cancer immunotherapy.", "b": "Marketed for tendon, muscle, and soft tissue recovery; studied as eye drops for dry eye (primary endpoints missed in a 72 patient trial).", "source_ids": [ "camerini-2015", "sosne-2015" ] }, { "name": "Safety", "a": "Mostly injection site redness and transient aches; no serious drug related events in the sepsis trial.", "b": "No systematic human safety data for the injectable; theoretical concern about supporting tumor growth because it drives cell migration and angiogenesis.", "source_ids": [ "chien-1998", "wu-2013", "goldstein-2012" ] }, { "name": "US compounding status", "a": "Placed in 503A Category 2 in 2023; FDA now lists the nomination as withdrawn, so it is not on the bulks list and has no lawful compounding basis.", "b": "Removed from 503A Category 2 on April 15, 2026; PCAC recommended adding it to the 503A bulks list on July 23 to 24, 2026; no final FDA rule at verification.", "source_ids": [ "fda-category-2", "fda-pcac-2026", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Unclear; not named on the list.", "b": "Prohibited at all times under S2, which names thymosin beta-4 and TB-500.", "source_ids": [ "wada-list" ] }, { "name": "Dosing reference", "a": "Trials used 1.6 mg subcutaneously twice weekly for 6 to 12 months (hepatitis B) or twice daily for 7 days (sepsis).", "b": "Not established for the injectable; the only human regimen is 0.1% eye drops for 28 days.", "source_ids": [ "chien-1998", "wu-2013", "sosne-2015" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Are thymosin alpha-1 and TB-500 the same thing?", "a": "No. Thymosin alpha-1 is a 28 amino acid immune modulator. TB-500 refers to thymosin beta-4 or a fragment of it, an actin binding peptide involved in cell migration and tissue repair. They share a name because both were first found in thymus extracts.", "source_ids": [ "dominari-2020", "goldstein-2012" ] }, { "q": "Which has better human evidence?", "a": "Thymosin alpha-1, which has randomized trials in hepatitis B and severe sepsis and is approved as Zadaxin abroad. TB-500 has no human trial of the injectable form; its only randomized human data are for eye drops in dry eye, where the primary endpoints were not met.", "source_ids": [ "chien-1998", "wu-2013", "sosne-2015" ] }, { "q": "Is TB-500 proven to heal injuries?", "a": "Not in humans. Rodent studies show faster wound closure and improved heart repair, but no human trial has tested injected TB-500 for tendon, muscle, or other musculoskeletal injuries.", "source_ids": [ "malinda-1999", "bock-marquette-2004", "sosne-2015" ] }, { "q": "Which can a US pharmacy compound?", "a": "Currently neither has a final bulks listing. TB-500 is closer: FDA removed it from Category 2 in April 2026 and PCAC recommended it for the bulks list in July 2026, so some pharmacies may fill it where state boards permit. Thymosin alpha-1's nomination is listed as withdrawn, leaving no lawful basis.", "source_ids": [ "fda-pcac-2026", "fda-category-2", "fda-503a-bulks" ] }, { "q": "Can athletes use them?", "a": "TB-500 is prohibited at all times under WADA section S2, which names thymosin beta-4. Thymosin alpha-1 is not named, so its status is unclear and athletes should check with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "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": "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-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" }, { "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" }, { "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" }, { "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" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "thymosin-alpha-1-vs-thymulin", "a": "thymosin-alpha-1", "b": "thymulin", "title": "Thymosin alpha-1 vs thymulin", "summary": "Thymosin alpha-1 has far more human evidence and real world use: randomized trials in chronic hepatitis B and severe sepsis, and approval as Zadaxin (thymalfasin) in more than 30 countries. Thymulin's human evidence is two small 1987 rheumatoid arthritis trials that were never replicated, and it is not approved anywhere. Neither has a lawful US access path today: thymosin alpha-1's compounding nomination was withdrawn, and thymulin was never nominated.", "verdict": { "winner": "a", "rationale": "Both technically sit at the human RCT grade, but thymosin alpha-1's base is broader and more recent: a 98 patient hepatitis B trial with 40.6% versus 9.4% virological response, a 361 patient sepsis trial with a 26.0% versus 35.0% mortality trend, and decades of use abroad with a benign safety record. Thymulin rests on one 1987 report of two trials. On regulation, thymosin alpha-1 is an approved drug in other countries while thymulin has no approval anywhere, though in the United States both lack any lawful compounding route.", "source_ids": [ "chien-1998", "wu-2013", "camerini-2015", "amor-1987", "fda-category-2", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Structure", "a": "28 amino acid N-acetylated peptide, a synthetic copy of a natural thymus derived immunomodulator.", "b": "9 amino acid peptide hormone from thymic epithelial cells that is active only when bound to zinc.", "source_ids": [ "dominari-2020", "dardenne-1982" ] }, { "name": "Mechanism", "a": "Acts on TLR2 and TLR9 on dendritic cells and T cell precursors, raising IL-2 and interferon, boosting natural killer and CD8 activity, and reducing T cell exhaustion markers.", "b": "Promotes T cell precursor differentiation and modulates T cell subsets and natural killer activity; linked to a thymus to neuroendocrine axis regulated by growth hormone and prolactin.", "source_ids": [ "dominari-2020", "liu-2020", "reggiani-2014" ] }, { "name": "Human trial evidence", "a": "Chronic hepatitis B RCT (98 patients): complete virological response 40.6% versus 9.4% at 18 months. Severe sepsis RCT (361 patients): 28 day mortality 26.0% versus 35.0% (relative risk 0.74, p = 0.062).", "b": "Two double blind, placebo controlled rheumatoid arthritis trials reported in 1987: 5 mg daily improved 56% of patients by global assessment versus 17% on placebo. No trial since.", "source_ids": [ "chien-1998", "wu-2013", "amor-1987" ] }, { "name": "Main clinical uses studied", "a": "Chronic hepatitis B and C, severe sepsis, severe COVID-19 (retrospective), vaccine adjuvant in dialysis and immunocompromised patients, and cancer immunotherapy.", "b": "Rheumatoid arthritis in humans; inflammation and neuropathic pain in rodents.", "source_ids": [ "camerini-2015", "liu-2020", "amor-1987", "safieh-garabedian-2019" ] }, { "name": "Approval status worldwide", "a": "Approved as Zadaxin (thymalfasin) in more than 30 countries; not FDA approved.", "b": "Not approved in any country.", "source_ids": [ "camerini-2015", "fda-503a-bulks" ] }, { "name": "US compounding status", "a": "Placed in 503A Category 2 in 2023; FDA now lists the nomination as withdrawn, so it is not in Category 2 and not on the bulks list, leaving no lawful compounding basis. Not part of the July 2026 PCAC review.", "b": "Never nominated: not on the 503A bulks list, Category 2, or the withdrawn list, and no USP monograph.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Unclear; not named on the list. Athletes should confirm with their anti-doping organization.", "b": "Prohibited at all times under S0 (non-approved substances).", "note": "Thymosin alpha-1 is an approved medicine in some countries, which is why it is not automatically captured by S0 the way thymulin is.", "source_ids": [ "wada-list" ] }, { "name": "Trial dosing", "a": "1.6 mg subcutaneously twice weekly for 6 to 12 months (hepatitis B); 1.6 mg twice daily for 7 days (sepsis).", "b": "1, 5, or 10 mg daily in the 1987 trials, with 5 mg most effective.", "source_ids": [ "chien-1998", "wu-2013", "amor-1987" ] }, { "name": "Safety record", "a": "Mostly injection site redness and transient aches; no significant side effects in the hepatitis B trial and no serious drug related events in the sepsis trial.", "b": "Minimal adverse effects in the 1987 trials; no modern human safety data.", "source_ids": [ "chien-1998", "wu-2013", "amor-1987" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which thymic peptide has better evidence?", "a": "Thymosin alpha-1. It has randomized trials in hepatitis B and sepsis and decades of use as an approved drug abroad, while thymulin's human evidence is limited to two small 1987 rheumatoid arthritis trials that were never repeated.", "source_ids": [ "chien-1998", "wu-2013", "camerini-2015", "amor-1987" ] }, { "q": "Can I get either one legally in the United States?", "a": "No lawful US path exists for either as of the verification date. Thymosin alpha-1's 503A nomination is listed by FDA as withdrawn and it is not on the bulks list; thymulin has never been nominated. Neither is FDA approved.", "source_ids": [ "fda-category-2", "fda-503a-bulks" ] }, { "q": "Did thymosin alpha-1 lower sepsis deaths?", "a": "The ETASS trial of 361 patients found 26.0% mortality with thymosin alpha-1 versus 35.0% with standard care alone, but the difference narrowly missed statistical significance (relative risk 0.74, 95% CI 0.54 to 1.02). It is a promising signal, not proof.", "source_ids": [ "wu-2013" ] }, { "q": "Why does thymulin need zinc?", "a": "Thymulin binds zinc in a one to one complex, and only the zinc bound form is biologically active, which was shown in 1982. That makes zinc status a factor in its activity.", "source_ids": [ "dardenne-1982", "bach-1989" ] }, { "q": "Are they allowed in sport?", "a": "Thymulin is prohibited at all times under WADA section S0. Thymosin alpha-1 is not named on the list, so its status is unclear, and athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] } ], "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": "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-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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 }, { "slug": "tirzepatide-vs-cagrilintide", "a": "tirzepatide", "b": "cagrilintide", "title": "Tirzepatide vs cagrilintide", "summary": "Tirzepatide is FDA approved and produced 20.9% weight loss at 15 mg in SURMOUNT-1. Cagrilintide alone produced 10.8% at 26 weeks in phase 2, and in combination with semaglutide 20.4% at 68 weeks in REDEFINE 1. The combination beat low dose tirzepatide (5 mg) on weight in type 2 diabetes in REIMAGINE 5 (12.4% versus 9.1% at 60 weeks, manufacturer topline). A 2026 network meta-analysis put tirzepatide and the combination at about the same one year weight loss.", "verdict": { "winner": "a", "rationale": "Tirzepatide is the only one that can be prescribed today and has cardiovascular outcomes data (SURPASS-CVOT). The combination of cagrilintide and semaglutide came close to it in a 2026 network meta-analysis but fell short of tirzepatide 15 mg in the direct REDEFINE 4 trial and beat the 5 mg tirzepatide dose in REIMAGINE 5, but that trial has not been published and the combination is still under FDA review. Cagrilintide alone is far less effective than tirzepatide.", "source_ids": [ "surmount-1", "surpass-cvot", "bmj-nma-2026", "reimagine-5-topline", "cagrisema-nda", "cagrilintide-phase2", "redefine-4-topline" ] }, "dimensions": [ { "name": "Mechanism", "a": "Dual GIP and GLP-1 receptor agonist.", "b": "Long acting amylin analog; developed mainly as a fixed combination with the GLP-1 agonist semaglutide.", "source_ids": [ "fda-zepbound-label", "cagrilintide-phase2", "redefine-1" ] }, { "name": "Weight loss evidence", "a": "15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg versus 3.1% on placebo at 72 weeks (SURMOUNT-1).", "b": "Alone: 10.8% at 4.5 mg versus 3.0% on placebo at 26 weeks. With semaglutide 2.4 mg: 20.4% versus 3.0% at 68 weeks (REDEFINE 1).", "source_ids": [ "surmount-1", "cagrilintide-phase2", "redefine-1" ] }, { "name": "Direct comparison", "a": "Tirzepatide 5 mg in REIMAGINE 5: 9.1% weight loss and HbA1c minus 1.67 points at 60 weeks in type 2 diabetes.", "b": "Cagrilintide plus semaglutide 1.0 mg each in REIMAGINE 5: 12.4% weight loss (superior) and HbA1c minus 1.71 points (noninferior).", "note": "Topline results announced by the manufacturer on September 21, 2026; not yet published in a journal, and the trial used the lowest tirzepatide maintenance dose.", "source_ids": [ "reimagine-5-topline" ] }, { "name": "Network meta-analysis", "a": "Mean difference versus lifestyle at one year minus 14.9% (moderate to high certainty); reduced heart failure risk.", "b": "Combination with semaglutide minus 14.8%; among the highest rates of discontinuation for adverse events and increased fatigue risk.", "source_ids": [ "bmj-nma-2026" ] }, { "name": "Cardiovascular outcomes", "a": "SURPASS-CVOT: noninferior to dulaglutide (hazard ratio 0.92) in 13,165 analyzed adults with type 2 diabetes and heart disease.", "b": "No cardiovascular outcomes trial has reported.", "source_ids": [ "surpass-cvot", "redefine-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Mounjaro 2022, Zepbound 2023).", "b": "Not FDA approved alone or in combination; a new drug application for cagrilintide 2.4 mg plus semaglutide 2.4 mg was submitted in December 2025. Not eligible for compounding.", "source_ids": [ "fda-zepbound-label", "cagrisema-nda", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited under section S0 while not approved by any regulator.", "source_ids": [ "wada-list" ] }, { "name": "Cost and access", "a": "Manufacturer self-pay for the KwikPen starts at 299 USD per 28 days at 2.5 mg; commercial savings card from 25 USD for a covered fill (checked 2026-09-22).", "b": "No lawful purchase channel outside clinical trials.", "source_ids": [ "mfr-savings-weight", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is CagriSema better than tirzepatide?", "a": "In REIMAGINE 5, cagrilintide plus semaglutide at 1.0 mg each produced 12.4% weight loss versus 9.1% with tirzepatide 5 mg at 60 weeks in type 2 diabetes, per the manufacturer's topline release. A 2026 network meta-analysis estimated nearly identical one year weight loss (14.8% versus 14.9% beyond lifestyle), but in REDEFINE 4, an open label 84 week trial in 809 adults with obesity and at least one related condition, cagrilintide plus semaglutide 2.4 mg each produced 23.0% weight loss versus 25.5% with tirzepatide 15 mg (efficacy estimand; 20.2% versus 23.6% by treatment regimen estimand) and did not meet its goal of showing non-inferiority to tirzepatide, per the manufacturer's topline release (not yet peer reviewed).", "source_ids": [ "reimagine-5-topline", "bmj-nma-2026", "redefine-4-topline" ] }, { "q": "How much weight loss does cagrilintide cause by itself?", "a": "10.8% at the 4.5 mg dose over 26 weeks in its phase 2 trial, about half of what tirzepatide 15 mg produced over 72 weeks in SURMOUNT-1.", "source_ids": [ "cagrilintide-phase2", "surmount-1" ] }, { "q": "Is the cagrilintide and semaglutide combination approved?", "a": "Not on the verification date. The manufacturer submitted a new drug application to FDA in December 2025.", "source_ids": [ "cagrisema-nda" ] }, { "q": "Which one is more likely to be stopped for side effects?", "a": "In the 2026 network meta-analysis, the cagrilintide and semaglutide combination was among the drugs with the highest discontinuation for adverse events, while tirzepatide was among those with the most gastrointestinal events.", "source_ids": [ "bmj-nma-2026" ] } ], "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-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": "bmj-nma-2026", "type": "pubmed", "title": "Nong K et al. Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis. BMJ 2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42419792/", "pmid": "42419792", "year": 2026 }, { "id": "reimagine-5-topline", "type": "other", "title": "Manufacturer press release: REIMAGINE 5 phase 3 topline results of cagrilintide plus semaglutide versus tirzepatide in type 2 diabetes, and REDEFINE 9 (September 21, 2026), accessed 2026-09-22", "url": "https://www.globenewswire.com/news-release/2026/09/21/3365319/0/en/novo-s-cagrisema-delivers-superior-weight-loss-versus-tirzepatide-in-reimagine-5-trial.html", "year": 2026 }, { "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 for weight management (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": "cagrilintide-phase2", "type": "pubmed", "title": "Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a randomised, placebo and active-controlled, dose-finding phase 2 trial. Lancet 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34798060/", "pmid": "34798060", "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" }, { "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": "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "mfr-savings-weight", "type": "other", "title": "Manufacturer self-pay and savings card page for tirzepatide for weight management, accessed 2026-09-22", "url": "https://zepbound.lilly.com/savings", "year": 2026 }, { "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "CagriSema vs tirzepatide (Zepbound): trial results", "description": "CagriSema vs tirzepatide: separate trial results for the amylin combination and Zepbound's ingredient, side effects, and which one is lawful today.", "h1": "Cagrilintide and CagriSema vs tirzepatide (Zepbound)" } }, { "slug": "tirzepatide-vs-dulaglutide", "a": "tirzepatide", "b": "dulaglutide", "title": "Tirzepatide vs dulaglutide", "summary": "Tirzepatide is the stronger drug for glucose and weight, and it now has a direct cardiovascular outcomes trial against dulaglutide: in SURPASS-CVOT (13,165 analyzed adults with type 2 diabetes and heart disease) it was noninferior, with events in 12.2% versus 13.1% (hazard ratio 0.92). In the phase 2 head-to-head trial, tirzepatide 15 mg lowered HbA1c 0.73 points more than dulaglutide 1.5 mg and cut up to 11.3 kg versus 2.7 kg. Dulaglutide remains a well studied diabetes-only option with a pediatric indication and fewer gastrointestinal side effects at high doses.", "verdict": { "winner": "a", "rationale": "Tirzepatide wins on direct evidence: a larger HbA1c and weight effect in a randomized phase 2 comparison, and cardiovascular noninferiority to dulaglutide in the SURPASS-CVOT outcomes trial, a comparator that itself reduced events in REWIND. It also carries weight management and sleep apnea indications that dulaglutide lacks. Both are FDA approved with human_rct evidence; dulaglutide still fits children 10 and older, people who tolerate GLP-1 only therapy better, and formularies that prefer it.", "source_ids": [ "surpass-cvot", "frias-2018", "rewind", "fda-zepbound-label", "fda-trulicity-label" ] }, "dimensions": [ { "name": "Cardiovascular outcomes (direct trial)", "a": "SURPASS-CVOT: major adverse cardiovascular events in 12.2% on tirzepatide up to 15 mg weekly (hazard ratio 0.92, 95.3% CI 0.83 to 1.01); noninferior, not statistically superior.", "b": "SURPASS-CVOT: 13.1% on dulaglutide 1.5 mg weekly. In the earlier placebo controlled REWIND trial dulaglutide reduced events (hazard ratio 0.88) over a median 5.4 years.", "source_ids": [ "surpass-cvot", "rewind" ] }, { "name": "Glucose and weight (direct trial)", "a": "Phase 2 (316 adults, 26 weeks): HbA1c minus 1.73 to minus 1.94 points at 5 to 15 mg; weight change up to minus 11.3 kg.", "b": "HbA1c minus 1.21 points and weight minus 2.7 kg on dulaglutide 1.5 mg in the same trial.", "source_ids": [ "frias-2018" ] }, { "name": "Mechanism", "a": "Single peptide that activates both GIP and GLP-1 receptors, half life about 5 days.", "b": "GLP-1 receptor agonist only: two GLP-1 analog chains fused to an IgG4 Fc fragment, half life about 5 days.", "source_ids": [ "fda-zepbound-label", "fda-trulicity-label" ] }, { "name": "FDA labeled indications", "a": "Mounjaro for type 2 diabetes; Zepbound for chronic weight management and moderate to severe obstructive sleep apnea with obesity.", "b": "Trulicity for type 2 diabetes in adults and children 10 and older, plus cardiovascular risk reduction in adults with type 2 diabetes. No weight management indication.", "source_ids": [ "fda-zepbound-label", "fda-trulicity-label" ] }, { "name": "Gastrointestinal side effects", "a": "Dose related: gastrointestinal events in 32.7% to 66.0% at 5 to 15 mg in the phase 2 trial; more gastrointestinal events than dulaglutide in SURPASS-CVOT.", "b": "Gastrointestinal events in 42.6% at 1.5 mg in the phase 2 trial; the most common reason for stopping in REWIND.", "note": "Both labels carry the thyroid C-cell tumor boxed warning and the medullary thyroid carcinoma and MEN 2 contraindication.", "source_ids": [ "frias-2018", "surpass-cvot", "rewind", "fda-trulicity-label" ] }, { "name": "Label dosing", "a": "2.5 mg weekly for 4 weeks, then 2.5 mg steps every 4 weeks to 5, 10, or 15 mg maintenance.", "b": "0.75 mg weekly, increased to 1.5 mg, then 3.0 and 4.5 mg after at least 4 weeks at each dose.", "source_ids": [ "fda-zepbound-label", "fda-trulicity-label" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (Mounjaro 2022, Zepbound 2023). Shortage resolved December 19, 2024; routine compounding ended February 18 (503A) and March 19, 2025 (503B).", "b": "FDA approved (Trulicity 2014). 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. Not available in bulk form, so not a compounded product.", "source_ids": [ "fda-glp1-compounding", "fda-trulicity-label", "fda-glp1-shortage-updates", "fda-drug-shortages-dulaglutide" ] }, { "name": "Typical cost", "a": "Zepbound list about 1,059 USD per month; manufacturer vials roughly 349 to 499 USD per month; about 25 USD with coverage and a savings card.", "b": "Trulicity list 1,006.93 USD per month (from 389 USD self-pay through the manufacturer pharmacy); often 25 USD with commercial coverage; covered by Medicare Part D for diabetes.", "note": "Prices at the verification date change often; see the cost pages.", "source_ids": [ "lillydirect", "fda-trulicity-label", "lilly-pricing-trulicity", "lillydirect-trulicity" ] } ], "head_to_head_studies": [ { "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 noninferiority trial", "n": 13165, "population": "Adults with type 2 diabetes and atherosclerotic cardiovascular disease", "outcome": "Cardiovascular death, myocardial infarction, or stroke in 12.2% with tirzepatide versus 13.1% with dulaglutide 1.5 mg (hazard ratio 0.92, 95.3% CI 0.83 to 1.01); noninferior, not superior", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/41406444/" }, { "pmid": "30293770", "title": "Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial", "year": 2018, "design": "Randomized, double blind, placebo and active comparator controlled phase 2 trial, 26 weeks", "n": 316, "population": "Adults with type 2 diabetes", "outcome": "HbA1c minus 1.73 to minus 1.94 points with tirzepatide 5 to 15 mg versus minus 1.21 with dulaglutide 1.5 mg; weight up to minus 11.3 kg versus minus 2.7 kg", "grade": "human_rct", "url": "https://pubmed.ncbi.nlm.nih.gov/30293770/" } ], "faqs": [ { "q": "Has tirzepatide been compared directly with dulaglutide?", "a": "Yes, twice. A 26 week phase 2 trial found larger HbA1c and weight reductions with tirzepatide 5 to 15 mg than with dulaglutide 1.5 mg, and the SURPASS-CVOT outcomes trial found tirzepatide noninferior to dulaglutide for cardiovascular death, heart attack, or stroke.", "source_ids": [ "frias-2018", "surpass-cvot" ] }, { "q": "Is tirzepatide better for the heart than dulaglutide?", "a": "It is at least as good. In SURPASS-CVOT, events occurred in 12.2% on tirzepatide and 13.1% on dulaglutide (hazard ratio 0.92), which met noninferiority but fell just short of statistical superiority. Dulaglutide itself had reduced events versus placebo in REWIND.", "source_ids": [ "surpass-cvot", "rewind" ] }, { "q": "Which causes more weight loss?", "a": "Tirzepatide. In the phase 2 comparison weight fell by up to 11.3 kg on tirzepatide versus 2.7 kg on dulaglutide 1.5 mg over 26 weeks, and only tirzepatide (as Zepbound) is approved for chronic weight management.", "source_ids": [ "frias-2018", "fda-zepbound-label" ] }, { "q": "Can children use either drug?", "a": "Dulaglutide (Trulicity) is FDA approved for type 2 diabetes in children 10 and older. Tirzepatide's labels are for adults.", "source_ids": [ "fda-trulicity-label", "fda-zepbound-label" ] }, { "q": "Which has more side effects?", "a": "Tirzepatide at higher doses. In the phase 2 trial gastrointestinal events rose from 32.7% at 5 mg to 66.0% at 15 mg, versus 42.6% with dulaglutide, and SURPASS-CVOT also reported more gastrointestinal events with tirzepatide.", "source_ids": [ "frias-2018", "surpass-cvot" ] } ], "sources": [ { "id": "surpass-cvot", "type": "pubmed", "title": "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": "frias-2018", "type": "pubmed", "title": "Frias JP et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a phase 2 trial. Lancet 2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30293770/", "pmid": "30293770", "year": 2018 }, { "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": "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" }, { "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" }, { "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" }, { "id": "lillydirect", "type": "other", "title": "Manufacturer self-pay page for tirzepatide for weight management, accessed 2026-09-22", "url": "https://lillydirect.lilly.com/" }, { "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "Mounjaro vs Trulicity (tirzepatide vs dulaglutide)", "description": "Mounjaro vs Trulicity: the SURPASS-CVOT heart outcome trial, blood sugar and weight results, label doses, pediatric use, and side effects, with sources.", "h1": "Mounjaro vs Trulicity (tirzepatide vs dulaglutide)" } }, { "slug": "tirzepatide-vs-liraglutide", "a": "tirzepatide", "b": "liraglutide", "title": "Tirzepatide vs liraglutide", "summary": "Tirzepatide produces far more weight loss than liraglutide in their respective trials: 20.9% at 15 mg over 72 weeks in SURMOUNT-1 versus about 8% at 3.0 mg over 56 weeks in SCALE, and it is injected weekly rather than daily. Liraglutide's advantages are that it is generic and cheaper, has the longest safety record in the class, and has a completed cardiovascular outcomes trial (LEADER). Both are FDA approved; no direct head-to-head trial has been published.", "verdict": { "winner": "a", "rationale": "Tirzepatide wins on efficacy by a margin that cross-trial uncertainty cannot erase: roughly 21% versus 8% weight loss in placebo-controlled trials, and superiority to semaglutide 1 mg on HbA1c in SURPASS-2, a drug that itself beat liraglutide directly. Liraglutide is the better pick when cost dominates (generic pens are on the market, tirzepatide has no generic) or when a prescriber wants a daily drug with a decades-long safety record and diabetes cardiovascular outcomes data.", "source_ids": [ "surmount-1", "surpass-2", "scale-obesity", "leader", "fda-first-generics" ] }, "dimensions": [ { "name": "Mechanism", "a": "Dual GIP and GLP-1 receptor agonist, half life about 5 days.", "b": "Selective GLP-1 receptor agonist, half life about 13 hours.", "source_ids": [ "fda-zepbound-label", "fda-saxenda-label" ] }, { "name": "Placebo-controlled weight loss", "a": "15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg vs 3.1% placebo at 72 weeks in SURMOUNT-1 (2,539 adults); 91% of the 15 mg group lost at least 5%.", "b": "8.4 kg vs 2.8 kg placebo at 56 weeks in SCALE Obesity and Prediabetes (3,731 adults); 63% vs 27% lost at least 5%.", "note": "No direct trial. Liraglutide lost to semaglutide 2.4 mg in STEP 8, and semaglutide 1 mg lost to tirzepatide in SURPASS-2.", "source_ids": [ "surmount-1", "scale-obesity", "step-8", "surpass-2" ] }, { "name": "Type 2 diabetes", "a": "SURPASS-2: HbA1c down 2.01 to 2.30 points vs 1.86 with semaglutide 1 mg at 40 weeks; approved as Mounjaro.", "b": "Victoza approved since 2010; SCALE Diabetes showed 6.0% weight loss at 3.0 mg vs 2.0% placebo in type 2 diabetes.", "source_ids": [ "surpass-2", "scale-diabetes", "fda-victoza-label" ] }, { "name": "Cardiovascular outcomes", "a": "No published placebo-controlled cardiovascular outcomes trial in obesity at the verification date; the Zepbound label carries no cardiovascular risk reduction indication.", "b": "LEADER: hazard ratio 0.87 for major adverse cardiovascular events and 0.78 for cardiovascular death in 9,340 adults with type 2 diabetes; Victoza carries a cardiovascular indication.", "source_ids": [ "fda-zepbound-label", "leader", "fda-victoza-label" ] }, { "name": "FDA labeled indications", "a": "Zepbound: chronic weight management and moderate to severe obstructive sleep apnea in adults with obesity. Mounjaro: type 2 diabetes.", "b": "Saxenda: chronic weight management (adults and adolescents 12 and older). Victoza: type 2 diabetes (adults and children 10 and older) and cardiovascular risk reduction.", "source_ids": [ "fda-zepbound-label", "fda-saxenda-label", "fda-victoza-label" ] }, { "name": "Route and dosing frequency", "a": "Subcutaneous injection once weekly; 2.5 mg start, 2.5 mg steps every 4 weeks to 5, 10, or 15 mg.", "b": "Subcutaneous injection once daily; 0.6 mg start, increased weekly by 0.6 mg to 3.0 mg (Saxenda).", "source_ids": [ "fda-zepbound-label", "fda-saxenda-label" ] }, { "name": "Common side effects", "a": "Nausea up to 31%, diarrhea up to 23%, vomiting up to 12%, constipation up to 12% at 15 mg in SURMOUNT-1; label advises a barrier contraceptive for 4 weeks after starting and after each dose increase.", "b": "Nausea, diarrhea, constipation, vomiting; heart rate up 2 to 3 beats per minute; serious adverse events 6.2% vs 5.0% placebo in SCALE.", "note": "Both carry the thyroid C-cell boxed warning and the same medullary thyroid carcinoma and MEN 2 contraindications.", "source_ids": [ "surmount-1", "fda-zepbound-label", "scale-obesity", "fda-saxenda-label" ] }, { "name": "Regulatory and compounding status", "a": "FDA approved (Mounjaro 2022, Zepbound 2023). Shortage-based compounding ended in early 2025; no generic.", "b": "FDA approved (Victoza 2010, Saxenda 2014). Generic liraglutide approved from December 2024. 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, and 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.", "source_ids": [ "fda-glp1-compounding", "fda-first-generics", "fda-saxenda-label", "fda-glp1-shortage-updates", "fr-2026-08552", "fda-drug-shortages-liraglutide" ] }, { "name": "Typical cost", "a": "Zepbound list price about 1,059 USD per month; manufacturer single-dose vials roughly 349 to 499 USD; about 25 USD with commercial coverage and a savings card.", "b": "Saxenda list price about 1,349 USD per month, but generic liraglutide at the diabetes strength runs roughly 200 to 500 USD cash; often 25 to 100 USD with commercial coverage.", "source_ids": [ "fda-zepbound-label", "fda-saxenda-label", "fda-first-generics" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "How much more weight loss does tirzepatide give than liraglutide?", "a": "Roughly two and a half times as much in their own trials: 20.9% at 15 mg over 72 weeks in SURMOUNT-1 versus about 8% at 3.0 mg over 56 weeks in SCALE. No trial has compared them directly, but the indirect chain (liraglutide lost to semaglutide in STEP 8, semaglutide 1 mg lost to tirzepatide in SURPASS-2) points the same way.", "source_ids": [ "surmount-1", "scale-obesity", "step-8", "surpass-2" ] }, { "q": "Why would anyone choose liraglutide over tirzepatide?", "a": "Price and track record. Generic liraglutide pens have been approved since December 2024 and can cost a few hundred dollars a month cash, while tirzepatide has no generic. Liraglutide also has 15 years of post-marketing experience and a completed cardiovascular outcomes trial in diabetes, and its daily dosing lets a prescriber stop it quickly if side effects appear.", "source_ids": [ "fda-first-generics", "leader", "fda-saxenda-label" ] }, { "q": "Are the side effects the same?", "a": "The same kind: gastrointestinal effects that peak during dose escalation, gallbladder and pancreatitis warnings, and the thyroid C-cell boxed warning. Tirzepatide's label adds a specific warning that oral contraceptives may be less effective for 4 weeks after starting or increasing the dose.", "source_ids": [ "fda-zepbound-label", "fda-saxenda-label", "surmount-1", "scale-obesity" ] }, { "q": "Which is better for the heart?", "a": "Liraglutide has the completed evidence: LEADER showed a 13% relative reduction in major adverse cardiovascular events in type 2 diabetes. Tirzepatide's Zepbound label carries no cardiovascular risk reduction indication at the verification date.", "source_ids": [ "leader", "fda-zepbound-label" ] }, { "q": "Can either be compounded?", "a": "Tirzepatide, not routinely: FDA ended the shortage-based allowance for compounded tirzepatide in early 2025. Liraglutide is different: 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. 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. Brand and generic liraglutide are also marketed, and on April 30, 2026 FDA proposed not to include liraglutide on the 503B bulks list. Ask any pharmacy offering compounded liraglutide which FDA rule it relies on.", "source_ids": [ "fda-glp1-compounding", "fda-first-generics", "fda-glp1-shortage-updates", "fr-2026-08552", "fda-drug-shortages-liraglutide" ] } ], "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": "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": "step-8", "type": "pubmed", "title": "Rubino DM et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35015037/", "pmid": "35015037", "year": 2022 }, { "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-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": "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 2, "seo": { "title": "Zepbound vs Saxenda (tirzepatide vs liraglutide)", "description": "Zepbound vs Saxenda: weekly tirzepatide against daily liraglutide on weight loss, heart data, side effects, generics, and cost, with sources.", "h1": "Zepbound vs Saxenda (tirzepatide vs liraglutide)" } }, { "slug": "tirzepatide-vs-mazdutide", "a": "tirzepatide", "b": "mazdutide", "title": "Tirzepatide vs mazdutide", "summary": "Tirzepatide is FDA approved and produced 20.9% weight loss at 72 weeks on 15 mg in SURMOUNT-1; mazdutide is a GLP-1 and glucagon dual agonist developed mainly in China that produced 14.0% at 48 weeks on 6 mg in GLORY-1 and 18.1% at 32 weeks on 16 mg in a US phase 2 trial. The weight numbers are in a similar range, but tirzepatide has far more trial data, US approval, and a cardiovascular outcomes trial, while mazdutide cannot be lawfully obtained in the United States outside a trial.", "verdict": { "winner": "a", "rationale": "Both have human_rct evidence, but tirzepatide's is larger (SURMOUNT-1 alone enrolled 2,539 adults for 72 weeks), it is FDA approved for diabetes, obesity, and sleep apnea, and it can be prescribed today. Mazdutide's high dose US data are promising but come from a 179 person, 32 week phase 2 trial, it has no FDA approval or lawful US compounding pathway, and it has no reported cardiovascular outcomes trial. No trial has compared the two directly.", "source_ids": [ "surmount-1", "fda-zepbound-label", "glory-1", "mazdutide-us-phase2", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Mechanism", "a": "Dual GIP and GLP-1 receptor agonist.", "b": "Oxyntomodulin analog that activates GLP-1 and glucagon receptors; glucagon activity adds energy expenditure and liver fat oxidation.", "source_ids": [ "fda-zepbound-label", "glory-1" ] }, { "name": "Obesity trial evidence", "a": "SURMOUNT-1 (2,539 adults, 72 weeks): 15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg versus 3.1% on placebo.", "b": "GLORY-1 (610 Chinese adults, 48 weeks): 11.0% and 14.0% at 4 and 6 mg versus plus 0.3% on placebo. US phase 2 (179 adults, 32 weeks): 7.3%, 15.6%, and 18.1% at 3 to 6, 10, and 16 mg versus 0.9%.", "note": "Cross-trial comparison only; populations, baseline BMI, and durations differ.", "source_ids": [ "surmount-1", "glory-1", "mazdutide-us-phase2" ] }, { "name": "Type 2 diabetes evidence", "a": "SURPASS-2 (1,879 adults, 40 weeks): HbA1c minus 2.01 to minus 2.30 points, beating semaglutide 1 mg.", "b": "Phase 2 (250 Chinese adults, 20 weeks): HbA1c minus 1.41 to minus 1.67 points versus minus 1.35 with dulaglutide 1.5 mg.", "source_ids": [ "surpass-2", "mazdutide-t2d-phase2" ] }, { "name": "Cardiovascular outcomes", "a": "SURPASS-CVOT versus dulaglutide in type 2 diabetes reported noninferiority in 2025.", "b": "No cardiovascular outcomes trial reported.", "source_ids": [ "surpass-cvot", "mazdutide-meta-2026" ] }, { "name": "Side effects", "a": "Nausea up to 31%, diarrhea up to 23%, vomiting up to 12% at 15 mg in SURMOUNT-1; thyroid C-cell boxed warning.", "b": "Diarrhea 36%, decreased appetite 29%, nausea 23%, vomiting 14% in the diabetes phase 2 trial; discontinuation for adverse events 1.5% or less in GLORY-1; heart rate increase from glucagon activity.", "source_ids": [ "surmount-1", "fda-zepbound-label", "mazdutide-t2d-phase2", "glory-1" ] }, { "name": "Regulatory status (United States)", "a": "FDA approved: Mounjaro (2022) and Zepbound (2023). Compounding allowance ended in early 2025 after the shortage resolved.", "b": "Not FDA approved; not a component of an approved drug and not on the 503A bulks list, so it cannot be compounded or dispensed in the US. 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-zepbound-label", "fda-glp1-compounding", "fda-503a-bulks", "mazdutide-china-obesity-approval", "mazdutide-china-t2d-approval" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Unclear: prohibited under section S0 wherever it is not approved; athletes should confirm with their anti-doping organization.", "source_ids": [ "wada-list" ] }, { "name": "Access and cost", "a": "Prescription at a retail pharmacy; Zepbound list about 1,059 USD per month, manufacturer vials roughly 349 to 499 USD.", "b": "No lawful US access outside a registered clinical trial; research chemical listings are not lawful for human use.", "source_ids": [ "lillydirect", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Is mazdutide stronger than tirzepatide?", "a": "There is no direct comparison. Tirzepatide 15 mg produced 20.9% weight loss at 72 weeks in SURMOUNT-1; mazdutide 16 mg produced 18.1% at 32 weeks in a smaller US phase 2 trial, and 6 mg produced 14.0% at 48 weeks in GLORY-1. Longer phase 3 data at high doses are needed before any ranking.", "source_ids": [ "surmount-1", "mazdutide-us-phase2", "glory-1" ] }, { "q": "How do they work differently?", "a": "Both activate the GLP-1 receptor. Tirzepatide adds GIP receptor activity, while mazdutide adds glucagon receptor activity, which raises energy expenditure and liver fat burning but can also raise heart rate.", "source_ids": [ "fda-zepbound-label", "glory-1" ] }, { "q": "Can I get mazdutide in the United States?", "a": "Not lawfully outside a clinical trial. It is not FDA approved, not a component of an approved drug, and not on the 503A bulks list, so pharmacies cannot compound it.", "source_ids": [ "fda-503a-bulks" ] }, { "q": "Which is better for type 2 diabetes?", "a": "Tirzepatide has the stronger and broader evidence, including SURPASS-2 against semaglutide and SURPASS-CVOT against dulaglutide. Mazdutide lowered HbA1c by 1.41 to 1.67 points in a 20 week phase 2 trial, slightly more than dulaglutide, but has no US approval.", "source_ids": [ "surpass-2", "surpass-cvot", "mazdutide-t2d-phase2" ] }, { "q": "Are either banned in sport?", "a": "Tirzepatide is not on the WADA Prohibited List. Mazdutide's status is unclear because it depends on whether it is approved anywhere; WADA section S0 prohibits substances without approval for human use, so athletes should treat it as prohibited unless told otherwise.", "source_ids": [ "wada-list" ] } ], "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": "surpass-cvot", "type": "pubmed", "title": "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": "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": "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" }, { "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" }, { "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" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List, including section S0 non-approved substances", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "lillydirect", "type": "other", "title": "Manufacturer self-pay page for tirzepatide for weight management, accessed 2026-09-22", "url": "https://lillydirect.lilly.com/" }, { "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), accessed 2026-09-27", "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), accessed 2026-09-27", "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 } ], "last_verified": "2026-09-27", "review_status": "draft", "version": 1 }, { "slug": "tirzepatide-vs-retatrutide", "a": "tirzepatide", "b": "retatrutide", "title": "Tirzepatide vs retatrutide", "summary": "Tirzepatide (Zepbound, Mounjaro) is the one you can actually be prescribed: it is FDA approved for type 2 diabetes, chronic weight management, and obstructive sleep apnea, with 20.9% weight loss at 15 mg over 72 weeks in SURMOUNT-1. Retatrutide, nicknamed reta or GLP-3 online, adds a third receptor (glucagon) and produced 24.2% weight loss at 12 mg over 48 weeks in phase 2 and 28.3% at 80 weeks in the TRIUMPH-1 phase 3 topline release, but it is investigational, cannot be compounded, and is prohibited in sport. There is no head-to-head trial.", "verdict": { "winner": "a", "rationale": "Tirzepatide wins on regulatory status and evidence maturity: it has approved labels, trials in thousands of participants, and a completed cardiovascular outcomes program, while retatrutide has phase 2 obesity data in a few hundred people, no approval anywhere, and no lawful access outside a clinical trial. Retatrutide's larger weight loss is real but comes from a smaller, shorter trial that is not directly comparable, and its glucagon activity raises heart rate more. If retatrutide is approved after the TRIUMPH phase 3 program, this verdict should be revisited.", "source_ids": [ "surmount-1", "retatrutide-phase2-obesity", "triumph-design", "fda-zepbound-label", "fda-glp1-compounding", "wada-list" ] }, "dimensions": [ { "name": "Mechanism", "a": "Dual GIP and GLP-1 receptor agonist.", "b": "Triple GIP, GLP-1, and glucagon receptor agonist; the glucagon component raises energy expenditure and liver fat oxidation.", "source_ids": [ "fda-zepbound-label", "retatrutide-phase2-obesity" ] }, { "name": "Weight loss in the pivotal trial", "a": "15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg vs 3.1% placebo at 72 weeks in SURMOUNT-1 (2,539 adults).", "b": "8.7%, 17.1%, 22.8%, and 24.2% at 1, 4, 8, and 12 mg vs 2.1% placebo at 48 weeks in the phase 2 trial (338 adults). TRIUMPH-1 phase 3 topline: 19.0%, 25.9%, and 28.3% at 4, 9, and 12 mg vs 2.2% placebo at 80 weeks (company release, not peer reviewed).", "note": "Different trials, populations, and durations; no head-to-head trial exists, so the numbers cannot be compared directly.", "source_ids": [ "surmount-1", "retatrutide-phase2-obesity", "triumph-1-topline" ] }, { "name": "Evidence maturity", "a": "Multiple phase 3 trials in obesity (SURMOUNT) and type 2 diabetes (SURPASS), including a head-to-head win over semaglutide 1 mg in SURPASS-2 and FDA review of the full data package.", "b": "Phase 2 in obesity and type 2 diabetes plus one published phase 3 type 2 diabetes trial (TRANSCEND-T2D-1, 537 adults, 40 weeks). Phase 3 obesity trials (TRIUMPH) have reported topline results by press release; full papers, FDA review, and a cardiovascular outcomes trial are still pending.", "source_ids": [ "surmount-1", "surpass-2", "retatrutide-phase2-t2d", "transcend-t2d-1", "triumph-design", "triumph-1-topline" ] }, { "name": "Regulatory status", "a": "FDA approved: Mounjaro (May 2022) and Zepbound (November 2023, sleep apnea indication added December 2024). Shortage-based compounding ended in early 2025.", "b": "Not approved by FDA or any other regulator. Not a component of an approved drug and not on the 503A bulks list, so it cannot lawfully be compounded. Only lawful access is a registered clinical trial.", "source_ids": [ "fda-zepbound-label", "fda-glp1-compounding", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited at all times under section S0 (non-approved substances).", "source_ids": [ "wada-list" ] }, { "name": "Side effects", "a": "Nausea up to 31%, diarrhea up to 23%, vomiting up to 12%, constipation up to 12% at 15 mg in SURMOUNT-1; boxed warning for thyroid C-cell tumors; pancreatitis and gallbladder disease warnings.", "b": "Dose-related nausea, diarrhea, vomiting, and constipation; a larger heart rate rise than GLP-1 only drugs, attributed to glucagon receptor activity; skin sensitivity and dysesthesia reported; long-term safety not established.", "source_ids": [ "surmount-1", "fda-zepbound-label", "retatrutide-phase2-obesity" ] }, { "name": "Route and dosing", "a": "Subcutaneous injection once weekly; label starts at 2.5 mg with 2.5 mg steps every 4 weeks to 5, 10, or 15 mg maintenance.", "b": "Subcutaneous injection once weekly in trials only; phase 2 used 1, 4, 8, or 12 mg maintenance after a 2 or 4 mg start. No approved dose exists.", "source_ids": [ "fda-zepbound-label", "retatrutide-phase2-obesity" ] }, { "name": "Typical cost", "a": "Zepbound list price up to 1,086.37 USD per fill; manufacturer self-pay vials or KwikPen 299 to 699 USD per month by dose (checked 2026-09-22); as little as 25 USD with commercial coverage and a savings card.", "b": "No lawful price. Trial participants receive it free. Products sold online as retatrutide are unapproved and unverified.", "source_ids": [ "price-info-weight", "retatrutide-phase2-obesity", "fda-glp1-compounding" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Retatrutide vs tirzepatide: which causes more weight loss?", "a": "In separate trials, yes: retatrutide 12 mg produced 24.2% weight loss at 48 weeks versus tirzepatide 15 mg at 20.9% over 72 weeks. But the retatrutide trial had 338 participants and the tirzepatide trial 2,539, and they were not compared directly, so the size of the true difference is unknown until phase 3 results are in.", "source_ids": [ "retatrutide-phase2-obesity", "surmount-1" ] }, { "q": "Can I get retatrutide instead of Zepbound or Mounjaro?", "a": "Not lawfully, outside a clinical trial. Retatrutide is not approved anywhere, is not on any FDA compounding list, and cannot be compounded. Tirzepatide is available by prescription as Mounjaro or Zepbound. Anything sold online as retatrutide is an unapproved drug with no verification of identity or dose.", "source_ids": [ "fda-glp1-compounding", "fda-503a-bulks", "fda-zepbound-label" ] }, { "q": "Is either banned for athletes?", "a": "Retatrutide is. Because it has no approval from any health authority, it falls under WADA section S0 and is prohibited at all times. Tirzepatide, as an approved GLP-1 based drug, is not on the Prohibited List.", "source_ids": [ "wada-list" ] }, { "q": "What is the difference in how they work?", "a": "Tirzepatide activates the GIP and GLP-1 receptors. Retatrutide activates those two plus the glucagon receptor, which increases energy expenditure and liver fat burning and is thought to explain the extra weight loss, at the cost of a bigger rise in heart rate.", "source_ids": [ "fda-zepbound-label", "retatrutide-phase2-obesity" ] }, { "q": "Which has better safety data?", "a": "Tirzepatide, by far. It has been through FDA review, has thousands of trial participants, and has an approved label with defined warnings. Retatrutide's safety is known only from trials of a few hundred people over about one year, with no cardiovascular outcomes trial reported.", "source_ids": [ "fda-zepbound-label", "surmount-1", "retatrutide-phase2-obesity" ] } ], "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": "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-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", "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", "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": "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 } ], "last_verified": "2026-09-23", "review_status": "draft", "version": 2, "seo": { "title": "Retatrutide vs tirzepatide: trial results and status", "description": "Retatrutide vs tirzepatide: phase 2 and phase 3 weight loss, how three receptors differ from two, side effects, and why only tirzepatide is lawful to prescribe.", "h1": "Retatrutide vs tirzepatide (Zepbound, Mounjaro)" } }, { "slug": "tirzepatide-vs-survodutide", "a": "tirzepatide", "b": "survodutide", "title": "Tirzepatide vs survodutide", "summary": "Tirzepatide has the larger weight loss and the stronger evidence base: 15.0% to 20.9% at 72 weeks in SURMOUNT-1 versus 12.2% to 13.0% at 76 weeks for survodutide in SYNCHRONIZE-1, plus FDA approval and a completed cardiovascular outcomes trial (SURPASS-CVOT). Survodutide is investigational, cannot be compounded, and is prohibited in sport; its main distinction is a phase 2 liver (MASH) signal.", "verdict": { "winner": "a", "rationale": "No trial has compared them directly, but tirzepatide's placebo-controlled weight loss is larger, it is approved for weight management, sleep apnea, and type 2 diabetes, and SURPASS-CVOT showed cardiovascular protection comparable to dulaglutide. Survodutide is not approved anywhere and is only available in trials.", "source_ids": [ "surmount-1", "synchronize-1", "surpass-cvot", "fda-zepbound-label", "fda-503a-bulks" ] }, "dimensions": [ { "name": "Mechanism", "a": "Dual GIP and GLP-1 receptor agonist.", "b": "Dual glucagon and GLP-1 receptor agonist.", "note": "Both are dual agonists, but the second receptor differs: GIP for tirzepatide, glucagon for survodutide.", "source_ids": [ "fda-zepbound-label", "synchronize-1" ] }, { "name": "Pivotal weight loss", "a": "15.0%, 19.5%, and 20.9% at 5, 10, and 15 mg versus 3.1% on placebo at 72 weeks (SURMOUNT-1, 2,539 adults).", "b": "12.2% (3.6 mg) and 13.0% (6.0 mg) versus 5.4% on placebo at 76 weeks (SYNCHRONIZE-1, 725 adults).", "note": "Cross-trial comparison; the trials used different estimands and populations.", "source_ids": [ "surmount-1", "synchronize-1" ] }, { "name": "Cardiovascular outcomes", "a": "SURPASS-CVOT: noninferior to dulaglutide for cardiovascular death, heart attack, or stroke (12.2% versus 13.1%, hazard ratio 0.92) in 13,165 analyzed adults with type 2 diabetes and heart disease.", "b": "No cardiovascular outcomes trial has reported.", "source_ids": [ "surpass-cvot", "synchronize-1" ] }, { "name": "Liver disease evidence", "a": "No MASH indication on the label.", "b": "Phase 2 MASH trial: improvement without worsening fibrosis in 47% to 62% versus 14% on placebo at 48 weeks.", "source_ids": [ "fda-zepbound-label", "survodutide-mash-phase2" ] }, { "name": "Tolerability", "a": "Nausea up to 31% at 15 mg versus 10% on placebo in SURMOUNT-1.", "b": "Gastrointestinal symptoms in 80.9% to 89.7% versus 47.9% on placebo in SYNCHRONIZE-1, mostly mild to moderate.", "source_ids": [ "surmount-1", "synchronize-1" ] }, { "name": "Regulatory status", "a": "FDA approved (Mounjaro 2022, Zepbound 2023). Shortage-based compounding ended in early 2025.", "b": "Investigational; not approved by any regulator and not eligible for compounding.", "source_ids": [ "fda-zepbound-label", "fda-shortage-clarification", "fda-503a-bulks" ] }, { "name": "WADA status", "a": "Not on the WADA Prohibited List.", "b": "Prohibited under section S0.", "source_ids": [ "wada-list" ] }, { "name": "Cost and access", "a": "Prescription only. Manufacturer self-pay for the KwikPen starts at 299 USD per 28 days at 2.5 mg, and a commercial savings card can bring a covered fill to 25 USD (checked 2026-09-22).", "b": "No lawful purchase channel; available only in registered clinical trials. Products sold as research chemicals are not lawful for human use.", "source_ids": [ "mfr-savings-weight", "fda-503a-bulks" ] } ], "head_to_head_studies": [], "faqs": [ { "q": "Which causes more weight loss, tirzepatide or survodutide?", "a": "Tirzepatide, based on separate trials: up to 20.9% at 72 weeks in SURMOUNT-1 versus 12.2% to 13.0% at 76 weeks for survodutide in SYNCHRONIZE-1. They have not been tested head to head.", "source_ids": [ "surmount-1", "synchronize-1" ] }, { "q": "Is survodutide better for the liver?", "a": "Its liver data are its strongest point: in a phase 2 MASH trial up to 62% improved versus 14% on placebo. Tirzepatide has no MASH indication, but survodutide is not approved for any use.", "source_ids": [ "survodutide-mash-phase2", "fda-zepbound-label" ] }, { "q": "Can survodutide be compounded like tirzepatide was?", "a": "No. Tirzepatide could be compounded only while it was in shortage, which ended in December 2024. Survodutide was never approved, is not on the 503A bulks list, and cannot lawfully be compounded at all.", "source_ids": [ "fda-shortage-clarification", "fda-503a-bulks" ] }, { "q": "Is either one banned in sport?", "a": "Survodutide is prohibited under WADA section S0 as a non-approved substance. Tirzepatide is not on the list.", "source_ids": [ "wada-list" ] } ], "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": "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": "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": "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" }, { "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" }, { "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": "fda-shortage-clarification", "type": "fda", "title": "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (shortage resolution and compounding end dates)", "url": "https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize" }, { "id": "wada-list", "type": "wada", "title": "WADA Prohibited List (section S0 covers substances not approved by any government health authority)", "url": "https://www.wada-ama.org/en/prohibited-list" }, { "id": "mfr-savings-weight", "type": "other", "title": "Manufacturer self-pay and savings card page for tirzepatide for weight management, accessed 2026-09-22", "url": "https://zepbound.lilly.com/savings", "year": 2026 } ], "last_verified": "2026-09-22", "review_status": "draft", "version": 1 } ], "meta": { "dataset": "comparisons", "generated_at": "2026-09-28T02:14:37.172Z", "data_as_of": "2026-09-27", "records": 75, "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" } }