Lilly Reports Two More Phase 3 Retatrutide Readouts, in Diabetes and Cardiovascular Disease

Eli Lilly and Company said on July 23, 2026 that retatrutide, an investigational once-weekly peptide, met its primary and key secondary endpoints in two additional Phase 3 trials from its TRIUMPH obesity program: TRIUMPH-2, conducted in adults with type 2 diabetes and obesity or overweight, and TRIUMPH-3, conducted in adults with severe obesity (BMI of 35 or higher) and established cardiovascular disease.

In TRIUMPH-2 (ClinicalTrials.gov identifier NCT05929079), the company reported that 1,152 participants were randomized across four groups. Under the efficacy estimand, average weight loss at 80 weeks was 12.7% (about 29.8 pounds) at the 4 mg dose, 19.1% (about 45.4 pounds) at 9 mg and 20.8% (about 49.6 pounds) at 12 mg, compared with 4.0% (about 9.3 pounds) for placebo. A1C reductions were 1.4, 1.6 and 1.5 percentage points at the three doses, respectively, versus 0.2 points for placebo.

In TRIUMPH-3 (ClinicalTrials.gov identifier NCT05882045), which randomized 1,949 participants in a 1:1:2 ratio, average weight loss at 80 weeks was 21.6% (about 52.7 pounds) at 9 mg and 22.6% (about 55.8 pounds) at 12 mg, compared with 3.2% (about 7.7 pounds) for placebo. Lilly also reported a secondary analysis of major adverse cardiovascular events (a five-component composite, MACE-5) in this cardiovascular-disease population, showing a hazard ratio of 0.82 favoring retatrutide, with a 95% confidence interval of 0.55 to 1.22. Because that interval crosses 1.0, the result does not establish a statistically significant reduction in cardiovascular events.

Lilly described the safety profile in both trials as consistent with the incretin drug class. In TRIUMPH-2, the most common adverse events were diarrhea (27.4% to 33.6% of participants across doses, versus 13.2% on placebo), nausea (13.7% to 28.0% versus 8.0%), constipation (14.0% to 16.8% versus 9.4%), decreased appetite (5.8% to 17.1% versus 4.5%) and vomiting (5.5% to 15.7% versus 4.2%). Discontinuations due to adverse events ranged from 3.8% to 11.6% in TRIUMPH-2 (versus 4.9% on placebo) and from 9.8% to 13.5% in TRIUMPH-3 (versus 4.8% on placebo).

"Across five positive Phase 3 studies, retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health, in the company's announcement. TRIUMPH-2 and TRIUMPH-3 are the fourth and fifth Phase 3 readouts from the program, following TRIUMPH-4 in knee osteoarthritis (December 2025), TRIUMPH-1 in general obesity (May 2026) and TRANSCEND-T2D-1 in type 2 diabetes (June 2026). Lilly said it plans to submit a Biologics License Application to the FDA in the first quarter of 2027.

The figures released on July 23 were topline results disclosed in a corporate announcement and had not yet been peer-reviewed or presented in full at a scientific meeting. Retatrutide remains investigational: it has not been approved by the FDA, the European Medicines Agency or any other regulator, and the trial data describe study outcomes rather than any authorized use.