Retatrutide's TRIUMPH-2 and TRIUMPH-3 report up to 22.6% weight loss in type 2 diabetes and established cardiovascular disease

On 23 July 2026, Eli Lilly reported topline results from TRIUMPH-2 and TRIUMPH-3, two phase 3 trials of retatrutide (LY3437943), an investigational once-weekly agonist at the GLP-1, GIP and glucagon receptors. Both trials met their primary weight-loss endpoints at 80 weeks. The findings extend the TRIUMPH programme beyond the TRIUMPH-1 obesity trial and the TRANSCEND-T2D-1 diabetes trial reported earlier in 2026.

TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes and obesity or overweight, randomised 1:1:1:1 to 4 mg, 9 mg, 12 mg or placebo. Mean weight loss was 12.7% (29.8 lb) at 4 mg, 19.1% (45.4 lb) at 9 mg and 20.8% (49.6 lb) at 12 mg, versus 4.0% (9.3 lb) on placebo. A1C fell by 1.4-1.6% across the retatrutide doses versus 0.2% on placebo.

TRIUMPH-3 enrolled 1,949 adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes, randomised 1:1:2 to 9 mg, 12 mg or placebo. Mean weight loss was 21.6% (52.7 lb) at 9 mg and 22.6% (55.8 lb) at 12 mg, versus 3.2% (7.7 lb) on placebo. In a pooled analysis of the two active doses, major adverse cardiovascular events (MACE-5) occurred in 44 retatrutide participants versus 52 on placebo, a hazard ratio of 0.82 (95% CI 0.55-1.22) — a confidence interval that crosses 1, so the trial does not establish a cardiovascular benefit.

The most common adverse events were gastrointestinal. In TRIUMPH-2 at 12 mg, rates were diarrhoea 33.6%, nausea 28.0%, decreased appetite 17.1%, constipation 16.8% and vomiting 15.7%, against lower placebo rates. Discontinuation due to adverse events was 7.7% at 12 mg versus 4.9% on placebo. In the cardiovascular-disease cohort of TRIUMPH-3, gastrointestinal event rates were somewhat lower, but discontinuation due to adverse events was higher at 13.5% (12 mg) versus 4.8% on placebo.

These are sponsor-reported topline figures; Lilly said detailed results will be presented at future medical meetings and published in peer-reviewed journals. The company reiterated plans to submit a Biologics License Application for retatrutide to the U.S. FDA in the first quarter of 2027. Retatrutide remains investigational and is not approved for any indication.