Retatrutide: Lilly reports TRIUMPH-2 and TRIUMPH-3 phase 3 results

On 23 July 2026, Eli Lilly reported topline results from two further phase 3 trials of retatrutide, its investigational once-weekly GIP, GLP-1 and glucagon receptor agonist ¹. The results were released by the company and had not been published in a peer-reviewed journal at the time of the announcement. Earlier phase 3 data from TRIUMPH-1 have been published ⁴ and are summarized in Amiravo's incretin pipeline overview.

TRIUMPH-2: type 2 diabetes with obesity or overweight

TRIUMPH-2 (NCT05929079) was an 80-week randomized, double-blind, placebo-controlled trial in adults with type 2 diabetes and obesity or overweight ^1,2. The registry lists 1,152 participants ², randomized equally to retatrutide 4 mg, 9 mg or 12 mg once weekly, or placebo ¹. Average baseline body weight was 106.4 kg and HbA1c 7.7% ¹.

Lilly reported mean body-weight change, using the efficacy estimand, of -12.7%, -19.1% and -20.8% across the three doses versus -4.0% with placebo ¹. HbA1c changed by -1.4%, -1.6% and -1.5% versus -0.2% ¹. Diarrhoea, nausea and decreased appetite were the most commonly reported adverse events; nausea, for example, was reported in 13.7% to 28.0% of retatrutide recipients versus 8.0% with placebo ¹. Discontinuation because of adverse events was 3.8%, 11.6% and 7.7% across the doses versus 4.9% with placebo ¹.

TRIUMPH-3: severe obesity with cardiovascular disease

TRIUMPH-3 (NCT05882045) enrolled adults with a BMI of at least 35 kg/m2 and established cardiovascular disease, with or without type 2 diabetes, and randomized them 1:1:2 to retatrutide 9 mg, 12 mg or placebo for 80 weeks ^1,3. Lilly reported 1,949 participants; the registry lists an actual enrollment of 1,946 ^1,3.

Mean body-weight change (efficacy estimand) was -21.6% and -22.6% versus -3.2% with placebo ¹. Lilly also reported cardiovascular events. For the pre-specified in-study MACE-5 outcome, there were 44 events with pooled retatrutide versus 52 with placebo (hazard ratio 0.82, 95% CI 0.55 to 1.22); for MACE-3, 27 versus 23 (hazard ratio 1.12, 95% CI 0.64 to 1.96) ¹. All confidence intervals included 1, so the trial did not show a difference in these events in either direction; it was not designed as a cardiovascular outcomes trial. Discontinuation because of adverse events was 9.8% and 13.5% versus 4.8% with placebo ¹.

Regulatory status

Lilly said it is completing the chemistry, manufacturing and controls package for a Biologics License Application and plans to submit retatrutide to FDA in the first quarter of 2027 ¹. Retatrutide is not approved by any regulator. FDA states that it cannot be used in compounding under federal law ⁵.

What this means for readers

• These are company-reported topline figures. Full methods, results under the treatment-regimen estimand and detailed safety data are expected in peer-reviewed publications.
• The efficacy estimand describes results as if participants stayed on treatment; it typically gives larger effects than an analysis that counts everyone randomized.
• Numbers from TRIUMPH-2 and TRIUMPH-3 apply to the populations and doses studied and cannot be extended to other settings.
• The retatrutide entry lists the trial literature and registry records.