Lilly's retatrutide reaches 30.3% average weight loss in Phase 3 TRIUMPH-1 trial

Retatrutide, an experimental once-weekly drug from Eli Lilly, produced average weight loss of up to 30.3% over 104 weeks in the Phase 3 TRIUMPH-1 trial, the company reported in May 2026. At the trial's 80-week primary endpoint, the highest dose tested, 12 mg, produced average weight loss of 28.3% ^[1].

What the trial found

TRIUMPH-1 (NCT05929066) enrolled 2,339 adults with obesity or overweight and at least one weight-related condition, but without diabetes. It was randomized, double-blind and placebo-controlled, and tested once-weekly retatrutide at 4 mg, 9 mg and 12 mg. All three doses met the primary and key secondary endpoints, according to the topline report ^[1].

At 80 weeks, participants on 12 mg lost an average of 70.3 lb, or 28.3%, from an average starting weight of 248.5 lb and a starting BMI of 40.0. The 9 mg group lost an average of 64.4 lb (25.9%), and the 4 mg group lost 47.2 lb (19.0%). The 4 mg dose requires a single titration step from the 2 mg starting dose ^[1].

In the 12 mg group, 45.3% lost at least 30% of their body weight, a threshold the report links to results historically associated with bariatric surgery. About 65.3% of that group finished with a BMI below 30, the cutoff for obesity, including 37.5% of participants who started with class 3 obesity (BMI of 40 or higher) ^[1].

Longer-term results and side effects

A prespecified, blinded extension followed 532 participants who began with a BMI of at least 35 and tolerated treatment; they could continue at a maximum tolerated dose of 9 mg or 12 mg. By week 104, those originally assigned to 12 mg had lost an average of 85.0 lb, or 30.3%, from an average starting weight of 268.3 lb and a BMI of 42.8 ^[1].

The 12 mg group also averaged a waist reduction of 24.1 cm (9.5 inches), with improvements in non-HDL cholesterol, triglycerides, systolic blood pressure and hs-CRP ^[1].

Retatrutide activates receptors for GIP, GLP-1 and glucagon, which makes it a triple agonist. It remains investigational, and no FDA approval has been announced ^[1][2].

Gastrointestinal effects were the most common. Nausea was reported by 28.6%, 38.4% and 42.4% of the 4 mg, 9 mg and 12 mg groups, compared with 14.8% on placebo. Diarrhea was reported by 25.2%, 34.1% and 32.0%, versus 13.5% on placebo; constipation by 23.8%, 25.9% and 26.1%, versus 10.9%; and vomiting by 10.6%, 22.8% and 25.3%, versus 4.8% ^[1].

Discontinuations because of side effects rose with dose: 4.1% at 4 mg, 6.9% at 9 mg and 11.3% at 12 mg, compared with 4.9% on placebo. Other reported events included upper respiratory and urinary tract infections and mild to moderate dysesthesia; most urinary and neurological cases resolved during active treatment ^[1].

In a separate Phase 3 trial, TRIUMPH-4, which enrolled adults with obesity or overweight and knee osteoarthritis, the 12 mg dose produced 28.7% average weight loss at 68 weeks and the 9 mg dose 26.4%, compared with 2.1% for placebo ^[2].

Why it matters for patients

Retatrutide cannot be prescribed today. It is investigational, and no approval or filing timeline has been reported ^[1][2]. People currently weighing GLP-1 options are choosing among drugs that are already on the market.

A review of 26 randomized trials covering 15,491 adults without diabetes had projected retatrutide at 24.2% weight loss at a 12 mg weekly dose, ahead of tirzepatide (17.8%) and injectable semaglutide (13.9%) at their highest evaluated doses ^[1]. Those figures come from a review of separate studies rather than head-to-head trials, so they are not direct comparisons. TRIUMPH-1 also enrolled people without diabetes, so its results do not describe outcomes in people with type 2 diabetes ^[1].

The reported averages also hide a wide range. At 12 mg, 45.3% of participants reached at least 30% weight loss, which means most did not. And higher doses brought more nausea, vomiting and discontinuations; the 4 mg dose produced less weight loss but had a discontinuation rate below placebo ^[1]. The 104-week extension included only participants who tolerated their treatment and started with a BMI of at least 35, so it does not represent everyone who began the trial ^[1].

What happens next

Lilly plans to present detailed TRIUMPH-1 data at the 86th annual American Diabetes Association Scientific Sessions; the report did not give a date ^[1]. Additional Phase 3 results are expected this year from TRIUMPH-2, which enrolled people with type 2 diabetes, and TRIUMPH-3, which enrolled people with established cardiovascular disease ^[1].

Lilly has said seven further Phase 3 readouts are expected in 2026, including studies of maintenance dosing strategies ^[2]. Whether any of those have reported since has not been disclosed.