TRIAL SUCCESS

Lilly's retatrutide cuts weight 22.6% in cardiovascular-disease patients

TRIUMPH-3 met its primary endpoint with up to 55.8 lbs lost at 80 weeks, and cardiovascular events trended lower without reaching significance, setting up a Q1 2027 BLA filing.

Eli Lilly reported that retatrutide met the primary endpoint in TRIUMPH-3, producing up to an average 55.8 lbs (22.6%) weight loss at 80 weeks in patients with severe obesity and established cardiovascular disease.

By AppliedXLJuly 23, 2026Trial NCT05882045

Executive Summary

Eli Lilly's Phase 3 TRIUMPH-3 trial met its primary weight-loss endpoint in adults with severe obesity and established cardiovascular disease, extending a run of positive retatrutide readouts into a sicker, comorbid population.
A pre-specified analysis of major cardiovascular events trended in retatrutide's favor but did not reach statistical significance, leaving the drug's effect on hard cardiovascular outcomes unresolved even as weight loss was confirmed.
Lilly intends to fold this trial into a first BLA filing for retatrutide, positioning the obesity indication as the lead use case ahead of related submissions in other conditions.
The result lands in an obesity field with a large and growing number of direct GLP-1R-class competitors, so the readout mainly reinforces retatrutide's position rather than establishing new separation.

The result

TRIUMPH-3 (NCT05882045) enrolled 1,946 adults with a body mass index of at least 35 kg/m2 and a history of myocardial infarction, ischemic or hemorrhagic stroke, or symptomatic peripheral arterial disease. The registered primary endpoint was percent change from baseline in body weight, and Lilly reported it was met, with participants on the two studied doses (9 mg and 12 mg) losing up to an average of 55.8 lbs, or 22.6%, at Week 80. Kenneth Custer, Lilly's executive vice president and president of Cardiometabolic Health, said the company now has "the clinical data package to support global submissions for retatrutide as a potential treatment for obesity, knee osteoarthritis pain, and obstructive sleep apnea". NCT05882045+1

Probability of Success

Endpoint Met100%

Completes99%

Clinical Significance87%

Regulatory95%

Cardiovascular events

The trial's pre-specified analysis of major adverse cardiovascular events, a composite of death, heart attack, stroke, heart failure, or coronary revascularization, recorded 44 events on pooled retatrutide doses versus 52 on placebo, a hazard ratio of 0.82 with a 95% confidence interval spanning 0.55 to 1.22. A narrower composite of cardiovascular death, heart attack, or stroke showed 27 events on retatrutide versus 23 on placebo, a hazard ratio of 1.12 with a confidence interval of 0.64 to 1.96. Both intervals cross 1.0, meaning neither the favorable nor unfavorable direction reached statistical significance. Lilly separately reported average reductions on the highest dose of 37.0% in triglycerides, 16.5% in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure, and 51.2% in high-sensitivity C-reactive protein, changes in cardiovascular risk markers rather than in the hard-outcome endpoint itself. Lilly's

Safety and trial history

Lilly described the safety profile as consistent with retatrutide's known tolerability, and TRIUMPH-3 is the trial's fifth positive Phase 3 readout for the molecule following TRIUMPH-1, TRIUMPH-2, and TRIUMPH-4. The trial's primary completion date moved five times over its life, from an original target in January 2026 to April 16, 2026, and enrollment was revised from 1,800 to 1,946 patients in the same May 2026 registry update, both changes recorded shortly before topline results were disclosed. The enrollment increase falls within the routine range for this design and phase, and does not indicate a change in trial conduct. Lilly's+1

Regulatory and competitive frame

Lilly plans to submit a Biologics License Application for retatrutide to the FDA in the first quarter of 2027, drawing on this trial along with TRIUMPH-1, TRIUMPH-2, and TRIUMPH-4. Retatrutide is a GLP-1R, GIPR, and GCGR triple agonist competing in a GLP-1R-class obesity field that includes at least 23 direct comparators in active development, among them Eli Lilly's own tirzepatide (marketed as Zepbound) and orforglipron, Novo Nordisk's semaglutide and zenagamtide, and Roche's enicepatide. Retatrutide is not first-in-class within this mechanism, since peer GLP-1R-class trials are active across multiple sponsors. Its Phase 3 obesity precedent, TRIUMPH-1, reported 28.3% weight loss at 80 weeks, so TRIUMPH-3's 22.6% figure in a cardiovascular-disease population sits close to that earlier result rather than exceeding it. Lilly's

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