Overview

Retatrutide is a synthetic peptide developed by Eli Lilly and Company as a once-weekly treatment candidate for obesity and related metabolic conditions. It is the first compound in late-stage development to act on three incretin and metabolic hormone receptors at once, which sets it apart from single agonists such as semaglutide and dual agonists such as tirzepatide.

• Research codeLY3437943
• ClassGIP / GLP-1 / glucagon triple agonist
• DeveloperEli Lilly and Company
• StagePhase 3 complete, not yet submitted

Mechanism of action

Each receptor target contributes a different effect, and the combination is thought to explain the size of the weight loss seen in trials.

• GLP-1 receptor. Slows gastric emptying, increases satiety and enhances glucose-dependent insulin secretion.
• GIP receptor. Augments insulin secretion and appears to improve tolerability and fat metabolism when paired with GLP-1 activity.
• Glucagon receptor. Raises energy expenditure and promotes hepatic fat oxidation, which may account for the additional fat loss and liver fat reductions observed.

Phase 2 evidence

The Phase 2 obesity trial, published in the New England Journal of Medicine in 2023, enrolled adults with obesity or overweight without diabetes. Participants in the highest-dose arm lost an average of about 24% of body weight at 48 weeks, a result that prompted the move into a large Phase 3 program.

Phase 3 TRIUMPH program

Lilly ran several pivotal trials across different populations. All four core TRIUMPH trials have now reported, alongside the TRANSCEND-T2D-1 diabetes trial.

Figures are topline results from the 12 mg arm as reported by the sponsor and medical press. Full peer-reviewed data for some trials are still being published.

Beyond weight loss

TRIUMPH-1 also reported a mean waist reduction of 24.1 cm at the top dose, along with improvements in non-HDL cholesterol, triglycerides, systolic blood pressure and hs-CRP. In TRIUMPH-4, knee pain scores fell by up to roughly three quarters from baseline, and a TRIUMPH-1 substudy reported large reductions in sleep apnoea severity.

Safety signals

The adverse event profile so far resembles other incretin-based drugs, with the most frequent events being gastrointestinal: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate and concentrated during dose escalation. A dose-dependent rise in resting heart rate was noted in Phase 2 and remains a point of interest. Long-term safety, including cardiovascular outcomes, is still under investigation in dedicated studies such as TRIUMPH-Outcomes.

Regulatory status

As of October 2026, retatrutide has not been approved anywhere. Lilly has said it plans to submit a Biologics License Application to the US FDA in the first quarter of 2027, with a decision likely to follow late in 2027 or in 2028. In August 2026 Lilly opened a limited pre-approval expanded access pathway for patients who meet specific medical criteria and cannot join a trial.

In Australia, retatrutide is not included on the Australian Register of Therapeutic Goods. Lilly has also publicly warned that products sold as retatrutide outside its trials may contain the wrong ingredient, an incorrect amount or contaminants, which is why independent purity testing matters for any research supply.

Laboratory handling

Like most lyophilised peptides, research-grade retatrutide is typically stored sealed, dry and refrigerated or frozen, protected from light and moisture. Request a batch-specific certificate of analysis showing HPLC purity and mass spectrometry identity confirmation, and follow your institution’s protocols for handling, storage and disposal.