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In clinical trials
Digestive & weight
Retatrutide
Also called LY3437943
Retatrutide is an investigational triple agonist of the GLP-1, GIP, and glucagon receptors. Learn how it works, what trials show, and where FDA approval stands.
- Reviewed by
- William Maish, MD MBA MPH, Clinical Product Lead
- Published
- April 18, 2026
- Last updated
- October 5, 2026
Key takeaway
Retatrutide is an investigational "triple agonist" that activates the GLP-1, GIP, and glucagon receptors, developed by Eli Lilly as a once-weekly injection for obesity, type 2 diabetes, and liver disease. In Phase 2 and Phase 3 trials it produced large, consistent weight reductions, and a Phase 2 substudy reported liver-fat reductions of more than 80% at 24 weeks. As of 2026 it is not yet approved, with an FDA filing targeted for 2027.
What is retatrutide?
Retatrutide is an experimental drug that activates three hormone receptors in a single molecule: GLP-1, GIP, and glucagon (sometimes called a "triple-G" agonist). It is being developed by Eli Lilly under the code LY3437943 as a once-weekly injection for obesity, type 2 diabetes, and related conditions including fatty liver disease. It is investigational and not yet approved.
How does it work?
Retatrutide combines three hormone actions. The GLP-1 and GIP receptors1 are incretin targets whose activation enhances glucose-dependent insulin release and reduces appetite. The third target, the glucagon receptor2, is the distinguishing feature: activating it is thought to increase energy expenditure and mobilize fat from the liver.
The idea is that adding glucagon action to the two incretin effects boosts weight loss and reduces liver fat beyond what incretin-only drugs achieve. This describes the proposed mechanism, which the trials below are designed to test.
Is it FDA-approved?
No. Retatrutide is investigational and not approved. According to Eli Lilly, following positive Phase 3 readouts the company plans to file with the FDA in 2027, a timeline it has attributed partly to manufacturing and quality verification.
What does the research show?
The evidence spans large, consistent trials. According to PubMed, the Phase 2 trials and the Phase 3 program reported these results:
| Study | Reported result |
| 48-week Phase 2 trial3 in obesity | Mean weight loss of around 24% at the highest dose versus about 2% with placebo |
| Phase 2 liver-fat substudy4 | Reductions in liver fat of more than 80% at 24 weeks |
| Phase 3 TRIUMPH-12 in obesity without diabetes | Mean weight loss of roughly 24-25% at the higher doses over 80 weeks |
| Phase 3 TRIUMPH-25 in obesity with type 2 diabetes | Roughly 17-19% weight loss, with improved blood sugar |
Gastrointestinal effects were the most common side effects and were dose-related. These results are consistent across replicated trials, though the drug is not yet approved.
Sources: the Phase 2 obesity trial (Jastreboff et al., New England Journal of Medicine, 2023, DOI: 10.1056/NEJMoa23019723); the Phase 2 liver-fat substudy (Sanyal et al., Nature Medicine, 2024, DOI: 10.1038/s41591-024-03018-24); TRIUMPH-1 (Jastreboff et al., New England Journal of Medicine, 2026, DOI: 10.1056/NEJMoa26041692); and TRIUMPH-2 (Bellido et al., The Lancet, 2026, DOI: 10.1016/S0140-6736(26)01861-15), all indexed on PubMed. This document is educational, is not medical advice or a health claim, and is not an offer to sell any product.