Retatrutide (code name LY3437943) is an investigational once-weekly injectable peptide from Eli Lilly. It activates three hormone receptors at once: those for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. That makes it a “triple agonist,” one step beyond tirzepatide (GIP and GLP-1) and semaglutide (GLP-1 only). It is being developed for obesity, type 2 diabetes and obesity-related conditions.
The single most important fact: retatrutide is not an approved drug. As of October 2026 it is still in phase 3 trials, and Lilly has said it plans to file for FDA approval in the first quarter of 2027. Phase 3 trials have reported mean weight loss of up to 25% over 80 weeks. Products sold online as “research peptides” are unapproved drugs in the eyes of the FDA, and lab tests have found their contents differ widely from the label.
This page summarizes what the published clinical trials, Lilly’s trial disclosures and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Triple GIP, GLP-1 and glucagon receptor agonist (fatty-acid-modified peptide) |
| Developer / code | Eli Lilly; LY3437943 |
| Route | Subcutaneous injection once weekly (in trials) |
| Doses studied | Phase 2: 0.5–12 mg/week; phase 3: maintenance doses of 4, 9 and 12 mg/week |
| Half-life | About 6 days (phase 1b trial) |
| Molecular weight | About 4,730 Da |
| Approval status | Not approved by the FDA; Lilly plans a Biologics License Application in Q1 2027; single-patient pre-approval expanded access opened in 2026 |
| US controlled-substance status | Not listed in DEA Schedule III (21 CFR 1308.13) |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances), prohibited at all times |
What it is
Retatrutide is a single peptide chain conjugated to a fatty diacid (a fat-like side chain) (Sanyal et al., Nat Med 2024). Lilly scientists described its discovery and first human dosing in 2022 (Coskun et al., Cell Metab 2022). A 2026 lab analysis gave the expected molecular weight of authentic retatrutide as 4,730.477 Da (Piatkowski et al., Drug Alcohol Rev 2026).
The discovery paper describes how the three targets divide the work:
| Receptor | Role described in the discovery paper (mouse data) |
|---|---|
| GLP-1 receptor | Reduces calorie intake |
| GIP receptor | Reduces calorie intake, together with GLP-1 receptor activity |
| Glucagon receptor | Increases energy expenditure, the component tirzepatide lacks |
In cell-based tests, retatrutide was less potent than the body’s own hormones at the human glucagon and GLP-1 receptors (0.3 and 0.4 times as active, respectively) and more potent at the human GIP receptor (by a factor of 8.9) (Sanyal et al., Nat Med 2024). In obese mice, adding glucagon-receptor-driven energy expenditure to the appetite reduction from the GIP and GLP-1 receptors produced more weight loss (Coskun et al., Cell Metab 2022). That mechanism is shown in animals; the human results are the trials below.
Pharmacokinetics
The key human pharmacokinetic data come from a 12-week phase 1b trial in 72 people with type 2 diabetes who received weekly doses from 0.5 mg up to an escalated 12 mg (Urva et al., Lancet 2022):
| Measure | Finding |
|---|---|
| Half-life | About 6 days |
| Dose proportionality | Exposure rose in proportion to dose |
| Dosing interval supported | Once weekly |
| Weight effect after a single dose | Weight reduction persisted up to day 43 in a single-dose study (Coskun et al., Cell Metab 2022) |
An anti-doping laboratory measured retatrutide in four people who self-administered 2 mg on days 1 and 7 (Carneiro et al., Rapid Commun Mass Spectrom 2026). The intact drug was found in plasma for about 56 days after the first dose, but neither the drug nor its breakdown products were detected in urine. The authors concluded that blood, not urine, is the right sample for detecting it.
Regulatory status
- Not approved. No country’s regulator had approved retatrutide as of a mid-2026 report (Piatkowski et al., Drug Alcohol Rev 2026). On July 23, 2026, Lilly said it plans to submit a Biologics License Application to the FDA in Q1 2027 (Lilly press release, 2026).
- Expanded access. In 2026 Lilly registered a pre-approval, single-patient expanded access program (ClinicalTrials.gov NCT07629401). It is limited to adults with a BMI of 35 or higher despite the highest available dose of approved weight-management drugs, two or more serious obesity-related complications, and no access to a retatrutide trial. Requests must come from a treating physician.
- FDA enforcement. FDA warning letters have called “Retatrutide” products sold by online vendors “unapproved new drugs” (FDA warning letter to Swisschems, December 10, 2024). A March 2026 letter stated that “Research Use Only” labeling did not change this, because the seller’s website showed the products were intended for human use (FDA warning letter to Gram Peptides, March 31, 2026).
- Controlled substances. Retatrutide is a peptide, not a steroid, and is not among the anabolic steroids listed in Schedule III (21 CFR 1308.13).
What the research shows
All of the trials below were funded by Eli Lilly. Results are mean changes, compared with placebo unless stated.
Obesity without diabetes: phase 2
The phase 2 trial randomized 338 adults with obesity (or overweight plus a weight-related condition) to weekly retatrutide at 1–12 mg or placebo for 48 weeks (Jastreboff et al., NEJM 2023):
| Weekly dose | Weight change at 24 weeks | Weight change at 48 weeks | Lost ≥15% at 48 weeks |
|---|---|---|---|
| Placebo | −1.6% | −2.1% | 2% |
| 1 mg | −7.2% | −8.7% | — |
| 4 mg (combined) | −12.9% | −17.1% | 60% |
| 8 mg (combined) | −17.3% | −22.8% | 75% |
| 12 mg | −17.5% | −24.2% | 83% |
In a substudy of 98 participants with fatty liver disease (MASLD, liver fat of 10% or more), liver fat fell by 82.4% at 24 weeks on 12 mg, versus a 0.3% rise on placebo (Sanyal et al., Nat Med 2024). Liver fat returned to the normal range (under 5%) in 86% of the 12 mg group and none of the placebo group.
Obesity without diabetes: phase 3 (TRIUMPH-1)
TRIUMPH-1 randomized 2,339 adults with obesity and without diabetes to 4, 9 or 12 mg/week or placebo for 80 weeks (Jastreboff et al., NEJM 2026). Subgroups with knee osteoarthritis (574 people) and obstructive sleep apnea (243 people) had their own primary outcomes.
| Outcome | Placebo | 4 mg | 9 mg | 12 mg |
|---|---|---|---|---|
| Body weight change at 80 weeks | −3.9% | −17.6% | −23.7% | −25.0% |
| Knee pain (WOMAC, 1–10 scale) | −1.9 | −3.2 | −3.5 | −3.6 |
| Apnea-hypopnea index (events/hour) | −9.9 | −22.9 | −34.3 | −31.7 |
The 9 mg and 12 mg groups lost 19.8 and 21.0 percentage points more weight than placebo (P under 0.001 for both). Pain and sleep-apnea figures are from the trial’s primary “hybrid” estimand; intention-to-treat results were similar. The most common adverse events were gastrointestinal.
Obesity with type 2 diabetes (TRIUMPH-2)
TRIUMPH-2 randomized 1,152 adults with a BMI of 27 or higher and type 2 diabetes across eight countries for 80 weeks (Bellido et al., Lancet 2026):
| Arm | Weight change at 80 weeks | Difference vs placebo (95% CI) |
|---|---|---|
| Placebo | −5.1% | — |
| 4 mg | −11.9% | −6.9% (−8.7 to −5.1) |
| 9 mg | −16.8% | −11.8% (−13.7 to −9.8) |
| 12 mg | −18.8% | −13.8% (−15.8 to −11.8) |
Weight loss was smaller than in TRIUMPH-1, which enrolled people without diabetes.
Obesity with cardiovascular disease (TRIUMPH-3, topline only)
Lilly reported topline results from TRIUMPH-3, an 80-week trial in 1,949 adults with a BMI of 35 or higher and established cardiovascular disease (Lilly press release, 2026). Weight fell by 21.6% on 9 mg and 22.6% on 12 mg, versus 3.2% on placebo. Cardiovascular events were few, and the pooled hazard ratio for a five-part major adverse cardiovascular event outcome was 0.82 (95% CI 0.55–1.22), which is not statistically significant. These results had not been peer-reviewed at the time of the release. A dedicated cardiovascular and kidney outcomes trial is still running (ClinicalTrials.gov NCT06383390).
Type 2 diabetes: blood sugar
| Trial | Design | HbA1c change | Weight change |
|---|---|---|---|
| Phase 2 (Rosenstock et al., Lancet 2023) | 281 adults; 0.5–12 mg vs placebo or dulaglutide 1.5 mg; 24/36 weeks | −2.02% on 12 mg vs −0.01% on placebo and −1.41% on dulaglutide (24 weeks) | −16.9% on 12 mg vs −3.0% on placebo (36 weeks) |
| TRANSCEND-T2D-1 (Bajaj et al., Lancet 2026) | 537 adults on diet and exercise alone; 4, 9 or 12 mg vs placebo; 40 weeks | −1.94% on 12 mg vs −0.81% on placebo | −15.3% on 12 mg vs −2.6% on placebo |
HbA1c is the average blood sugar over the past 2–3 months. No severe hypoglycemia (dangerously low blood sugar) was reported in either trial.
Body composition: fat versus lean mass
Retatrutide is not an anabolic agent, and no trial has tested it in lean or resistance-trained people. A DXA substudy of the phase 2 diabetes trial measured fat loss directly (Coskun et al., Lancet Diabetes Endocrinol 2025):
| Arm | Total fat mass change at 36 weeks |
|---|---|
| Placebo | −4.5% |
| Dulaglutide 1.5 mg | −2.6% |
| Retatrutide 4 mg (pooled) | −15.2% |
| Retatrutide 8 mg (pooled) | −26.1% |
| Retatrutide 12 mg | −23.2% |
The authors reported that lean mass made up a share of total weight lost similar to that seen with other obesity treatments. In other words, part of the weight lost is still lean tissue. Only 103 participants had both baseline and week-36 scans, so these estimates are imprecise.
Kidney markers
A post hoc analysis of the two phase 2 trials found that 12 mg lowered urine albumin-to-creatinine ratio (a marker of kidney damage) by 37.0% (95% CI 7.0–57.3) versus placebo in people with type 2 diabetes (Heerspink et al., Kidney Int Rep 2025). Most participants had normal urine albumin at baseline, so the absolute change was modest.
Side effects and risks
There is no approved label, so there is no official list of warnings, contraindications or interactions. What is known comes from trials lasting up to 80 weeks.
Gastrointestinal effects
Nausea, diarrhea, vomiting and constipation were the most common adverse events in every trial. They were dose-related, mostly mild to moderate, and occurred mainly during dose escalation (Sanyal et al., Nat Med 2024). In phase 2, starting at 2 mg rather than 4 mg partly reduced them (Jastreboff et al., NEJM 2023). TRIUMPH-2 reported these rates (Bellido et al., Lancet 2026):
| Adverse event | Placebo | 4 mg | 9 mg | 12 mg |
|---|---|---|---|---|
| Diarrhea | 13% | 27% | 34% | 34% |
| Nausea | 8% | 14% | 21% | 28% |
| Hypotension (low blood pressure) | under 1% | 1% | 5% | 6% |
| Dysesthesia (abnormal skin sensations) | 1% | 4% | 6% | 7% |
| Stopped treatment due to adverse events or death | 5% | 4% | 12% | 8% |
In TRIUMPH-3, Lilly reported treatment discontinuation due to adverse events of 9.8% on 9 mg and 13.5% on 12 mg, versus 4.8% on placebo. Dysesthesia (abnormal skin sensations) occurred in 6.4% of people on each retatrutide dose, versus 1.3% on placebo (Lilly press release, 2026).
Heart rate
In the phase 2 obesity trial, heart rate rose in a dose-dependent way, peaked at 24 weeks and declined thereafter (Jastreboff et al., NEJM 2023). Long-term cardiovascular safety will be settled by the ongoing outcomes trial, not by the trials published so far.
Deaths in trials
In TRIUMPH-2, six participants on retatrutide and one on placebo died; investigators judged all deaths unrelated to the study drug (Bellido et al., Lancet 2026). TRANSCEND-T2D-1 reported two deaths, both in the 4 mg group and judged unrelated (Bajaj et al., Lancet 2026).
Unregulated “research” products
Because retatrutide cannot be prescribed, nearly all use outside trials involves unregulated products.
- Wrong dose. Three vials labeled 10 mg, bought in Australia and tested in an accredited lab, all contained retatrutide, but in amounts of 5.13 mg, 16.5 mg and 19.0 mg, or 51–190% of the label (Piatkowski et al., Drug Alcohol Rev 2026). Sterility and endotoxins were not tested.
- Case reports. A woman in her mid-20s was hospitalized with persistent vomiting after four weekly injections of a product said to contain retatrutide, given in a wellness setting by a person without medical training (Buzzi and Huber, BMJ Case Rep 2026). A man with type 1 diabetes developed severe vomiting, ketosis and acute kidney injury after injecting an online product, with a concurrent Shigella infection making causation uncertain (Branine, Cureus 2026). Retatrutide has no established role in type 1 diabetes.
Who it has not been studied in
The published trials enrolled adults with obesity, overweight or type 2 diabetes, and lasted up to 80 weeks. No published controlled trial has tested retatrutide in athletes or trained lifters, or in people with type 1 diabetes.
Use in sport
Retatrutide is not named on the WADA Prohibited List. However, the S0 class bans “any pharmacological substance” not covered elsewhere on the List that has no current approval by any government health authority, explicitly including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved investigational drug, retatrutide falls into that class and is prohibited at all times. Its status could change if a regulator approves it. A validated blood test can detect it for weeks after use (Carneiro et al., Rapid Commun Mass Spectrom 2026).
Key takeaways
- A triple agonist, not an approved drug. Retatrutide activates GIP, GLP-1 and glucagon receptors. As of October 2026 it is still investigational, with an FDA filing planned for Q1 2027.
- Large weight loss in phase 3. In the phase 3 TRIUMPH-1 trial, adults without diabetes lost an average of 25.0% of body weight at 80 weeks on 12 mg, versus 3.9% on placebo.
- Smaller effect with diabetes. In TRIUMPH-2, people with type 2 diabetes lost 18.8% on 12 mg, versus 5.1% on placebo.
- Side effects rise with dose. Gastrointestinal effects dominate. Dysesthesia, low blood pressure and a heart-rate rise that peaked at 24 weeks were also reported, and up to 12–14% of people on higher doses stopped because of adverse events.
- Not a muscle builder. It reduces fat mass, and part of the weight lost is lean tissue. No trial has studied it in lean or trained people.
- Gray-market products are unreliable. The FDA treats online “research use only” retatrutide as an unapproved drug, and tested vials held 51–190% of the labeled amount.
Sources
- Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234–1247.e9. PubMed.
- Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022;400(10366):1869–1881. PubMed.
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity – a phase 2 trial. N Engl J Med. 2023;389(6):514–526. PubMed.
- Rosenstock J, Frias J, Jastreboff AM, et al. 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. Lancet. 2023;402(10401):529–544. PubMed.
- Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037–2048. PubMed; PMC.
- Coskun T, Wu Q, Schloot NC, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Lancet Diabetes Endocrinol. 2025;13(8):674–684. PubMed.
- Heerspink HJL, Lu Z, Du Y, et al. The effect of retatrutide on kidney parameters in participants with type 2 diabetes mellitus and/or obesity. Kidney Int Rep. 2025;10(6):1980–1992. PubMed.
- Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. Published online September 29, 2026. doi:10.1056/NEJMoa2604169. PubMed.
- Bellido V, le Roux CW, Ekinci EI, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;408(10563):1455–1472. PubMed.
- Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. 2026;407(10546):2402–2413. PubMed.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release, July 23, 2026. BioSpace.
- Eli Lilly and Company. Pre-approval expanded access of retatrutide (LY3437943). ClinicalTrials.gov NCT07629401. ClinicalTrials.gov.
- US Food and Drug Administration. Warning letter to Swisschems, MARCS-CMS 695663, December 10, 2024. FDA.
- US Food and Drug Administration. Warning letter to Gram Peptides, MARCS-CMS 721806, March 31, 2026. FDA.
- Piatkowski T, Craven A, Cornell S, Ferris J. Composition and labelling accuracy of products sold as retatrutide in Australia. Drug Alcohol Rev. 2026;45(6):e70231. PubMed.
- Buzzi RM, Huber LC. Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide. BMJ Case Rep. 2026;19(10):e276106. PubMed.
- Branine N. Online-sourced retatrutide complicating impending diabetic ketoacidosis in a patient with type 1 diabetes and concurrent Shigella gastroenteritis. Cureus. 2026;18(8):e115260. PubMed.
- Carneiro GRA, da Costa Nunes IK, Dos Santos Cardoso GR, et al. Detection and excretion profile of retatrutide in human plasma and urine by LC-HRMS: implications for antidoping analysis. Rapid Commun Mass Spectrom. 2026;40(23):e70179. PubMed.
- Eli Lilly and Company. The effect of retatrutide once weekly on cardiovascular outcomes and kidney outcomes in adults living with obesity (TRIUMPH-Outcomes). ClinicalTrials.gov NCT06383390. ClinicalTrials.gov.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.