Phase 3 TRIUMPH-1 (2,339 participants) met its primary and key secondary endpoints; in the highest-dose arm, 45.3% of participants lost more than 30% of their body weight.
adults with obesity or overweight and at least one weight-related condition
Retatrutide
Investigational
Metabolic
Retatrutide
An investigational GIP, GLP-1 and glucagon agonist
Investigational · not approved · not available for sale or prescriptionOverview.
Retatrutide is an investigational drug from Eli Lilly and is not approved anywhere as of September 2026. It is an injectable that activates the GIP, GLP-1 and glucagon receptors. Phase 2 and phase 3 obesity trials have reported weight loss compared with placebo, with gastrointestinal side effects the most common adverse events. Lilly plans to submit it to FDA in the first quarter of 2027.
Also known as LY3437943
The molecule, decoded.
- Sequence
-
Y-[Aib]-QGTFTSDYSI-[alpha-Me-Leu]-LDK-[Lys(AEEA-gammaGlu-C20 diacid)]-AQ-[Aib]-AFIEYLLEGGPSSGAPPPS-NH2
- Length
- 39 residues
- Molecular weight
- 4,731.3 g/mol
- Formula
- C221H342N46O68
- CAS number
- 2381089-83-2
- Half-life
- ~6 days (approx. 134-165 hours across phase 1 dose groups)
- Routes studied
- subcutaneous injection
- Modifications
- Aib at positions 2 and 20; alpha-methyl-Leu at position 13; C-terminal amide; C20 fatty diacid conjugated at Lys17 via a gamma-Glu and one AEEA linker for albumin binding
How it works.
A 39-amino-acid single-molecule agonist engineered to activate glucagon (GCGR), GIP (GIPR), and GLP-1 (GLP-1R) receptors, binding human GCGR/GIPR/GLP-1R with EC50 of 5.79/0.0643/0.775 nM respectively. Combined incretin action plus glucagon-receptor-driven increases in energy expenditure and hepatic fat oxidation add a thermogenic/lipolytic effect on top of appetite suppression and glucose control.
Evidence · Phase 3 clinical trials
What the research shows
Phase 3 TRIUMPH-3 (1,949 adults with severe obesity, BMI 35 or higher, and established cardiovascular disease, with or without type 2 diabetes) reported 21.6-22.6% mean weight loss in the two retatrutide dose groups vs 3.2% with placebo at 80 weeks (efficacy estimand); major cardiovascular events did not differ significantly (MACE-3 HR 1.12, 95% CI 0.64-1.96).
adults with BMI >=35 and established CVD, with or without T2D
At the highest dose, 11.3% of participants stopped treatment because of adverse events in TRIUMPH-1 (vs 4.9% on placebo) and 18.2% in TRIUMPH-4 (vs 4.0%). Gastrointestinal events were most common (nausea 42.4% and 43.2%; diarrhea 32.0% and 33.1%), and dysesthesia (abnormal skin sensation) occurred in 12.5% and 20.9%.
TRIUMPH-1 (n=2,339) and TRIUMPH-4 (n=445) participants
In a phase 2 dose-ranging trial, retatrutide produced up to 24.2% mean weight loss at 48 weeks (highest-dose arm).
adults with obesity/overweight, phase 2
Retatrutide engages GCGR in vivo and improves glucose tolerance in mice, and produces substantial body-weight loss and increased energy expenditure via glucagon-receptor activation in diet-induced obese mice.
CD-1 and diet-induced-obese C57/Bl6 mice
What to know first.
Based on: published clinical trials.
Reported side effects
- nausea
- diarrhea
- vomiting
- constipation
- decreased appetite
- dysesthesia (abnormal skin sensation; 4.5-20.9% across TRIUMPH trials vs 0.7-1.3% on placebo)
- urinary tract infections (above placebo in most arms)
- injection site reactions
- increased heart rate (mild, class-associated)
Cautions
- not FDA-approved, so it has no FDA label
- gallbladder-related events reported in phase 2 (~1.1% vs 0% placebo)
- pancreatitis reported in small numbers in phase 2, insufficient to establish or exclude causal risk
- GI adverse events are dose-dependent and concentrate during dose titration
Checked 2026-09
Where it stands.
Investigational · not approved · not available for sale or prescription. Retatrutide is an investigational drug still in clinical trials. It is not approved and not available for sale or prescription. The legitimate way to access it is by enrolling in a clinical trial. Find trials on ClinicalTrials.gov
- FDA
- investigational (not approved anywhere); Lilly plans a BLA/NDA submission to FDA in Q1 2027
- Compounding
- Not eligible for compounding: retatrutide is not a component of any FDA-approved drug and is in no 503A category, and FDA states it cannot be used in compounding under federal law. Gray-market or 'compounded' retatrutide has no legal compounding pathway.
- Sport (WADA)
- Prohibited at all times (in and out of competition) under S0 Non-Approved Substances: retatrutide is not named on the WADA 2026 Prohibited List, but S0 covers any pharmacological substance with no current approval by any regulatory authority for human therapeutic use (e.g., drugs in clinical development). Not approved anywhere as of Sep 2026. The 2027 List (published 21 Sep 2026) adds 'peptides' to the S0 examples.
- Enforcement
- FDA states retatrutide cannot be used in compounding under federal law and has warned telehealth companies (including for direct-to-consumer marketing), API distributors selling retatrutide to compounders, and outsourcing facilities repackaging retatrutide (FDA GLP-1 concerns page, current as of Sep 1, 2026)