What is retatrutide?
Retatrutide is an investigational (still in clinical trials) once weekly injected peptide that activates three hormone receptors at once, GIP, GLP-1, and glucagon; online it is nicknamed "reta" or "GLP-3", but there is no GLP-3 hormone, and the nickname only reflects its three targets. In a 48 week phase 2 trial of 338 adults with obesity, the 12 mg dose produced a mean 24.2% weight loss versus 2.1% on placebo, and the manufacturer's TRIUMPH-1 phase 3 topline release reported 28.3% at 80 weeks. As of September 2026 it is not FDA approved or approved anywhere else, cannot lawfully be compounded (custom-made by a pharmacy), and is prohibited in sport under WADA section S0.
What is Retatrutide?
Retatrutide is an investigational triple agonist of the GIP, GLP-1, and glucagon receptors (single acylated peptide, once weekly). It is also known as LY3437943, triple agonist, GIP/GLP-1/glucagon triple receptor agonist, reta, reta peptide, GLP-3, GLP-3 peptide.
How does it work?
Retatrutide is a single peptide engineered to activate three receptors. GLP-1 receptor activation reduces appetite, slows gastric emptying, and increases glucose dependent insulin release. GIP receptor activation adds appetite and insulin effects. Glucagon receptor activation increases energy expenditure and liver fat oxidation, which is thought to explain the larger weight loss than GLP-1 or GIP/GLP-1 agonists alone, at the cost of a small rise in heart rate. It is acylated for a roughly one week half life.
| Cluster | GLP-1 and incretin agonists |
|---|---|
| Routes | Subcutaneous injection once weekly (clinical trials only) |
| Conditions studied | Obesity and chronic weight management; Type 2 diabetes; Obstructive sleep apnea; Osteoarthritis |
| Record | v3, draft, verified Sep 23, 2026 |
What does the evidence say about Retatrutide?
Phase 2 randomized controlled trials in obesity (n = 338, 48 weeks) and type 2 diabetes (n = 281, 36 weeks) plus a phase 3 type 2 diabetes trial (TRANSCEND-T2D-1, n = 537, 40 weeks) published in 2026. In the obesity trial, weight loss at 48 weeks was 8.7%, 17.1%, 22.8%, and 24.2% at 1, 4, 8, and 12 mg versus 2.1% on placebo. Phase 3 obesity trials (TRIUMPH) have reported topline results by company press release, including 28.3% at 80 weeks in TRIUMPH-1 and 28.7% at 68 weeks in TRIUMPH-4, not yet peer reviewed. No cardiovascular outcomes trial has reported.
| Evidence type | Indexed studies | Participants (human) |
|---|---|---|
| Human randomized trials | 4 | 1228 |
| Human observational studies | 0 | n/a |
| Animal studies | 0 | n/a |
| All indexed studies | 4 | 1,228 |
Human evidence
Phase 2 obesity trial: 338 adults with BMI 30 or higher (or 27 to 30 with a weight related condition), 48 weeks; least squares mean weight change minus 8.7% (1 mg), minus 17.1% (4 mg), minus 22.8% (8 mg), minus 24.2% (12 mg) versus minus 2.1% (placebo). At 12 mg, 100% lost at least 5%, 93% at least 10%, and 83% at least 15%. Phase 2 type 2 diabetes trial: 281 adults, 36 weeks, retatrutide up to 12 mg versus placebo and dulaglutide 1.5 mg, with clinically meaningful HbA1c and weight reductions; a DXA substudy showed most of the weight lost was fat mass. TRANSCEND-T2D-1: 537 adults with type 2 diabetes on diet and exercise alone, 40 weeks, retatrutide 4, 9, or 12 mg versus placebo, with significant improvements in glycemic control and weight.
Animal evidence
Preclinical rodent and primate pharmacology established the triple receptor binding profile and the additive effect of glucagon receptor agonism on energy expenditure. Thyroid C cell findings in rodents are expected to apply as with other GLP-1 based agonists; formal labeling has not been issued because the drug is not approved.
Key studies
| Study | Design and population | Outcome | Grade |
|---|---|---|---|
| Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial2023 PMID 37366315 | Randomized, double blind, placebo controlled phase 2 trial, 48 weeksn = 338 Adults with BMI 30 or higher, or 27 to less than 30 with a weight related condition, without diabetes | Mean weight change at 48 weeks minus 8.7% (1 mg), minus 17.1% (4 mg), minus 22.8% (8 mg), minus 24.2% (12 mg) versus minus 2.1% (placebo) | Evidence: Human RCT evidence |
| Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial2023 PMID 37385280 | Randomized, double blind, placebo and active (dulaglutide) controlled phase 2 trial, 36 weeksn = 281 Adults with type 2 diabetes on diet and exercise or stable metformin | Clinically meaningful HbA1c and body weight reductions versus placebo and dulaglutide 1.5 mg; safety consistent with GLP-1 class | Evidence: Human RCT evidence |
| Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a phase 3 trial2026 PMID 42250575 | Randomized, double blind, placebo controlled phase 3 trial, 40 weeksn = 537 Adults with type 2 diabetes inadequately controlled by diet and exercise alone | Significant improvements in glycemic control and body weight at 4, 9, and 12 mg weekly versus placebo | Evidence: Human RCT evidence |
| LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b multiple-ascending dose trial2022 PMID 36354040 | Phase 1b randomized, double-blind, placebo-controlled multiple ascending dose trial, 12 weeksn = 72 Adults with type 2 diabetes | Half life about 6 days, supporting once weekly dosing; dose dependent reductions in glucose, HbA1c, and body weight; gastrointestinal events most common | Evidence: Human RCT evidence |
Conditions studied
| Condition | Grade | Note |
|---|---|---|
| Obesity and chronic weight management | Evidence: Human RCT evidence | Phase 2 trials published; phase 3 ongoing; not FDA approved. |
| Type 2 diabetes | Not graded | Several peptide drugs are FDA approved for type 2 diabetes, including insulin, GLP-1 receptor agonists, tirzepatide, and pramlintide. GLP-1 agonists and tirzepatide lower HbA1c by about 1 to 2 percentage points and reduce weight; semaglutide also reduces cardiovascular events. |
| Obstructive sleep apnea | Evidence: No published evidence | Its phase 3 program includes an obstructive sleep apnea study, but no OSA results have been published; not approved. |
| Osteoarthritis | Evidence: No published evidence | Its phase 3 program includes knee osteoarthritis pain endpoints; no osteoarthritis results in our sources yet; not approved. |
Is Retatrutide legal in the United States?
FDA and compounding status
Not FDA approved and not approved by any other regulator as of the last verification date. Because retatrutide is not a component of an approved drug, has no USP monograph, and is not on the 503A bulks list, it cannot lawfully be compounded by 503A pharmacies or 503B outsourcing facilities. FDA has warned that unapproved GLP-1 class products sold online, including investigational molecules, are not evaluated for safety, quality, or dose. Any product sold as retatrutide outside a clinical trial is unlawful for human use.
WADA status
WADA prohibited. Athletes subject to anti-doping testing should treat this as prohibited at all times unless the current prohibited list says otherwise.
Regulatory timeline
No regulatory events recorded.
What published studies of Retatrutide used
Ranges below are reported from published studies and labeling only. PeptideAgent does not recommend doses or protocols.
Phase 2 obesity trial: once weekly subcutaneous injection escalated to maintenance doses of 1, 4, 8, or 12 mg, with starting doses of 2 or 4 mg and escalation every 4 weeks. Phase 3 type 2 diabetes trial: 4, 9, or 12 mg weekly. No approved label exists; these are trial regimens only.
Routes reported
| # | Route |
|---|---|
| 1 | Subcutaneous injection once weekly (clinical trials only) |
Retatrutide safety in trials: a summary
Side effects
| # | Reported side effect |
|---|---|
| 1 | Nausea, diarrhea, vomiting, and constipation (dose related, mostly mild to moderate, partly mitigated by lower starting dose) |
| 2 | Increased heart rate, greater than with GLP-1 only agonists, attributed to glucagon receptor activity |
| 3 | Dysesthesia (abnormal skin sensation) in 12.5% on 12 mg versus 0.9% on placebo in the TRIUMPH-1 topline release |
| 4 | Skin sensitivity and dysesthesia reported in the phase 2 trial |
| 5 | Decreased appetite |
| 6 | Long term safety not established; no cardiovascular outcomes trial reported as of last verification |
Interactions
| # | Interaction |
|---|---|
| 1 | No approved label, so no formal interaction studies are published |
| 2 | Class effects expected: hypoglycemia with insulin or sulfonylureas, and altered absorption of oral drugs from delayed gastric emptying |
| 3 | Should not be combined with other GLP-1 based agonists (not studied) |
Contraindications
| # | Contraindication |
|---|---|
| 1 | Not approved for any use; only available inside registered clinical trials |
| 2 | Personal or family history of medullary thyroid carcinoma or MEN2 (trial exclusion criteria, class precaution) |
| 3 | Pregnancy and breastfeeding (excluded from trials) |
| 4 | Competitive athletes subject to WADA testing (prohibited under S0) |
Can you get retatrutide legally?
Typical cost: Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.
Verified access options
Step 1
No lawful United States access path identified on the last verified date outside a registered clinical trial.
Step 2
Not available as an FDA approved product and not eligible for compounding under section 503A or 503B while investigational.
Step 3
Products labeled research use only are not lawful for human use and are not verified for identity or purity.
Access paths are verified against public regulatory records and prescriber licensing. We never list unlicensed vendors.
Compare Retatrutide
What's actually offered, and what that means for you
Licensed compounding pharmacies, clinics, and telehealth prescribers openly offer many unapproved peptides, and prescribers write prescriptions for them. That does not make retatrutide lawful. Retatrutide is not FDA approved and not on the 503A bulks list, so a pharmacy has no lawful basis to compound it. [6]
Enforcement is uneven. FDA mostly acts through warning letters to online sellers and import alerts that let it detain shipments, rather than stopping every seller. State pharmacy boards oversee pharmacies day to day, and their rules differ. [13] [14] [15]
What changes for you
- No FDA review of the product: a product sold outside a trial is an unapproved drug, and FDA has not checked its safety, effectiveness, or quality. [13]
- Identity, purity, sterility, and dose accuracy can vary from batch to batch. [13]
- Insurance rarely covers it, so you usually pay cash.
- For tested athletes, retatrutide is prohibited at all times on the WADA list, whatever the source. [7]
What to check
Retatrutide is not approved in the US, and no check makes a product sold outside a clinical trial lawful. Check for:
- Enrollment in a registered clinical trial (ClinicalTrials.gov lists them). Outside a trial, any product sold as retatrutide is an unapproved drug.
- Labels such as "research use only" or "not for human consumption", which FDA does not accept for products sold for people. [13]
- A licensed prescriber's view on whether an approved drug fits your goal.
For weight management, approved GLP-1 drugs such as tirzepatide and semaglutide are available by prescription. See Tirzepatide, Semaglutide, GLP-1 hub.
Frequently asked questions
Is retatrutide legal?
Not for sale or prescription. Retatrutide is investigational and not approved by FDA or any other regulator as of September 2026, and the manufacturer says it is legally available only to participants in its clinical trials. It cannot be compounded because it is not a component of an approved drug and is not on any FDA bulks list. Products sold online as retatrutide are unapproved drugs with no verification of identity or dose. [5] [6] [8]
Why is retatrutide called reta or GLP-3?
Reta is shorthand for retatrutide. GLP-3 is an online nickname, not a scientific name: there is no hormone called GLP-3. The nickname points to its three targets, since retatrutide activates the GIP, GLP-1, and glucagon receptors, one more than tirzepatide and two more than semaglutide. Trial papers call it retatrutide or by its development code, LY3437943. [4] [11]
Retatrutide before and after: what did the trials measure?
Trials measured average change in body weight, not individual photos. In the phase 2 trial of 338 adults, mean weight change at 48 weeks was minus 24.2% on 12 mg versus minus 2.1% on placebo, and 83% on 12 mg lost at least 15%. In the TRIUMPH-1 phase 3 topline release, adults without diabetes on 12 mg lost 28.3% at 80 weeks versus 2.2% on placebo, and in TRIUMPH-4, adults with knee osteoarthritis lost 28.7% at 68 weeks. In type 2 diabetes (TRANSCEND-T2D-1), weight fell 11.5% to 15.3% at 40 weeks versus 2.6%. The phase 3 obesity figures are company releases, not yet peer reviewed. [1] [3] [8] [9]
What safety signals did retatrutide trials report?
Gastrointestinal effects dominate, as with other GLP-1 based drugs. In the TRIUMPH-1 topline release, nausea affected 42.4% on 12 mg versus 14.8% on placebo, with diarrhea, constipation, and vomiting also common. Dysesthesia, an abnormal skin sensation, occurred in 12.5% on 12 mg versus 0.9% on placebo, and 11.3% on 12 mg stopped for adverse events versus 4.9% on placebo. Heart rate rises more than with GLP-1 only drugs because of the glucagon activity. Long term safety and cardiovascular outcomes are not yet known. [1] [8]
Is retatrutide an injection or a pill?
An injection. Every published phase 2 and phase 3 trial gave retatrutide as a once weekly injection under the skin, and no oral version has been tested in a published trial. Products sold online as retatrutide capsules, drops, or pills are unapproved and unverified, and FDA has warned about unapproved GLP-1 products sold online. Among approved weight management drugs, semaglutide is available as a daily tablet (Wegovy tablets). [1] [4] [5] [12]
How long does retatrutide stay in your system?
Its half life was about 6 days in a phase 1b trial, which is what allows once weekly dosing. Blood levels fall by roughly half every 6 days after a last dose, so it takes several weeks to clear, and in the first single dose study weight reduction persisted up to day 43 after one injection. No approved label exists, so there is no official guidance on stopping before surgery or pregnancy. [10] [11]
Retatrutide vs tirzepatide: what is the difference?
Tirzepatide (Zepbound, Mounjaro) activates two receptors (GIP and GLP-1) and is FDA approved; retatrutide adds a third (glucagon) and is investigational. In their separate trials, retatrutide 12 mg produced 24.2% weight loss at 48 weeks in phase 2 versus tirzepatide 15 mg at 20.9% over 72 weeks, and no head-to-head trial exists. Retatrutide raises heart rate more because of its glucagon activity. Until FDA reviews the phase 3 data and approves it, tirzepatide is the only one of the two a patient can lawfully be prescribed. [1] [5]
Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.
From the blog
- How to get retatrutide: clinical trials, expanded access, and the law
Retatrutide is not approved, so a clinical trial is the only lawful way to get it. How to search ClinicalTrials.gov, how expanded access works, and why online and compounded sources are unlawful.
- Retatrutide before and after: weight loss by dose and week in the trials
What retatrutide trials measured: 24.2% mean weight loss at 48 weeks in phase 2, up to 28.3% at 80 weeks in phase 3, and what happened to fat, waist size, and blood sugar.
- Retatrutide benefits beyond weight loss: liver fat, blood sugar, and blood pressure
What retatrutide trials measured besides weight: liver fat, HbA1c, blood pressure, lipids, fat mass, and knee pain. What is proven, what is post hoc, and what is still unknown.
- Retatrutide side effects: what the trials reported, dose by dose
Nausea, diarrhea, dysesthesia, heart rate, and dropouts in the retatrutide trials, with placebo rates. What the data say about safety, and what is still unknown.
- Retatrutide: where the phase 3 program stands
Five phase 3 readouts, one peer-reviewed paper, and no approval yet. What the retatrutide trials have shown, what is still pending, and why no one can lawfully sell it today.
- Are peptide injections safe? What is known and unknown
FDA-approved peptide injections have documented side effects on their labels. Compounded and research-only peptides add unknowns: sterility, identity, dose accuracy, and contamination.
More on the blog
Sources
Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.
- [1]Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023PubMed 37366315, 2023
- [2]Rosenstock J et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial. Lancet 2023PubMed 37385280, 2023
- [3]Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial. Lancet 2026PubMed 42250575, 2026
- [4]Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab 2026PubMed 41090431, 2026
- [5]FDA: concerns with unapproved GLP-1 drugs used for weight lossFDA, 2025
- [6]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)FDA, 2026
- [7]WADA Prohibited List, section S0 non-approved substancesWADA, 2026
- [8]Manufacturer press release: topline results of the TRIUMPH-1 phase 3 trial of retatrutide (May 21, 2026), not peer reviewed2026
- [9]Manufacturer press release: topline results of the TRIUMPH-4 phase 3 trial of retatrutide in obesity and knee osteoarthritis (December 11, 2025), not peer reviewed2025
- [10]Urva S et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet 2022PubMed 36354040, 2022
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<a href="https://peptideagent.ai/peptides/retatrutide">Retatrutide: evidence, legality, and access</a>, PeptideAgent, updated September 23, 2026.