Lilly publishes full TRIUMPH-2 Phase 3 retatrutide data in The Lancet, up to 18.8% weight loss in type 2 diabetes

Eli Lilly released detailed results from TRIUMPH-2, a Phase 3 trial of its investigational triple hormone receptor agonist retatrutide, in adults with type 2 diabetes and obesity or overweight. The data were presented September 29, 2026, at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan and published the same day in The Lancet ^[1][2].

TRIUMPH-2 randomized 1,152 adults 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg or placebo, given as a once-weekly injection for 80 weeks ^[1]. Participants started at 2 mg weekly and stepped up every four weeks to their assigned target dose ^[1]. Average starting weight was 234.6 lbs (106.4 kg), average BMI was 38.2, and average A1C was 7.7% ^[1][4].

What the trial found

At week 80, average weight loss was 12.7% (29.8 lbs) on 4 mg, 19.1% (45.4 lbs) on 9 mg and 20.8% (49.6 lbs) on 12 mg, compared with 4.0% (9.3 lbs) on placebo ^[1]. Among people who started with a BMI of 35 or higher, those on 12 mg lost an average of 60.8 lbs (23.4%) ^[1]. By the end of the trial, 59.5% of the 12 mg group no longer met the BMI criteria for obesity ^[1].

These figures come from what Lilly calls the efficacy estimand, which estimates results as if everyone had stayed on treatment without starting other weight-management drugs ^[1][3]. Results that count everyone enrolled, including people who stopped, are usually somewhat lower ^[4].

On blood sugar, A1C fell by an average of 1.4 percentage points on 4 mg, 1.6 on 9 mg and 1.5 on 12 mg, versus 0.2 on placebo — with no clear dose-dependent effect ^[1][3]. Up to 79.2% of retatrutide participants reached an A1C of 6.5% or lower, compared with 26.3% on placebo, and up to 40.0% got below 5.7%, versus 4.4% on placebo ^[1]. At the top dose, Lilly also reported average reductions of 39.5% in triglycerides, 19.6% in non-HDL cholesterol, 10.8 mmHg in systolic blood pressure, 6.7 inches (16.9 cm) in waist circumference and 58.3% in high-sensitivity C-reactive protein ^[1].

The most common side effects on retatrutide (4 mg, 9 mg, 12 mg vs. placebo) were diarrhea (27.4%, 33.5%, 33.6% vs. 13.2%), nausea (13.7%, 20.8%, 28.0% vs. 8.0%), constipation, decreased appetite and vomiting ^[1]. Dysesthesia — unusual skin sensations such as tingling or burning — occurred in 4.5%, 5.6% and 7.3% versus 0.7% on placebo ^[1][4]. Discontinuations due to adverse events were 3.8% (4 mg), 11.6% (9 mg) and 7.7% (12 mg), versus 4.9% on placebo ^[1].

Why it matters for patients

Retatrutide acts on three receptors — GIP, GLP-1 and glucagon — while semaglutide (Ozempic, Wegovy, Rybelsus) acts on GLP-1 and tirzepatide (Mounjaro, Zepbound) acts on GIP and GLP-1 ^[4]. TRIUMPH-2 is the first full peer-reviewed Phase 3 dataset for the drug in a diabetes population, and it suggests larger average weight loss in this group than has typically been reported for existing options: 34.9% of the 12 mg group lost at least 25% of body weight, and 52.0% lost at least 20%, compared with 34% losing at least 20% at week 72 in a Phase 3 tirzepatide trial ^[1][3]. The blood-sugar effect looks more modest by comparison; in an earlier trial, up to 55.3% of tirzepatide patients got below 5.7% A1C ^[3]. No completed head-to-head trial has compared retatrutide with approved drugs, so direct comparisons are not established ^[4].

Practically, none of this changes what is available today. Retatrutide is investigational, cannot be legally prescribed, purchased or compounded, and is available only in clinical trials ^[4]. Products sold online as "retatrutide peptide" are not legitimate and are not tested for safety, purity or dose ^[4]. Long-term safety has not been established, and a dedicated cardiovascular outcomes trial is still ongoing ^[4].

What happens next

Lilly said it plans to submit a Biologics License Application to the FDA in the first quarter of 2027 ^[1][3]. FDA review can take up to about a year depending on the review type, and no approval or launch date has been set ^[4]. Results from the obstructive sleep apnea portion of TRIUMPH-2 will be presented at a future medical meeting and published later; a date has not been disclosed ^[1].