Lilly's Retatrutide Meets All Weight-Loss Goals in Phase 3 TRIUMPH-1 Trial

Eli Lilly said on May 21 that retatrutide, its investigational once-weekly injection that activates GIP, GLP-1 and glucagon receptors, met the primary and key secondary endpoints of TRIUMPH-1, a Phase 3 trial in adults with obesity or overweight and at least one weight-related condition but without diabetes, according to the company's announcement, distributed by PR Newswire and read via BioSpace.

The figures are company-reported topline results. Lilly said more detailed data will be presented at medical meetings and published in peer-reviewed journals.

The TRIUMPH-1 results

TRIUMPH-1 (NCT05929066) is an 80-week, randomized, double-blind, placebo-controlled trial that assigned 2,339 participants in equal numbers to retatrutide 4 mg, 9 mg or 12 mg, or placebo. Participants started at 2 mg and stepped up every four weeks to their target dose.

In the primary efficacy analysis, participants lost an average of 19.0% of body weight on 4 mg, 25.9% on 9 mg and 28.3% on 12 mg, from an average starting weight of 112.7 kg (248.5 lbs). On the 12 mg dose, 45.3% of participants lost at least 30% of their body weight, the company said. Lilly's efficacy estimand assumes participants stayed on the study drug; in its treatment-regimen analysis, which counts everyone regardless of adherence, weight loss was 17.6%, 23.7% and 25.0% on the three doses, versus 3.9% on placebo.

A pre-specified blinded extension enrolled 532 participants with a starting body mass index of at least 35 who had completed 80 weeks. Those who began on 12 mg lost an average of 30.3% of body weight by week 104, according to Lilly. AJMC reported that the 12 mg group's waist circumference fell by an average of 24.1 cm, alongside changes in non-HDL cholesterol, triglycerides, systolic blood pressure and hs-CRP.

Kenneth Custer, president of Lilly Cardiometabolic Health, said the 12 mg dose "delivered a level of weight loss long associated with bariatric surgery."

Side effects

The most common adverse events were gastrointestinal. Nausea occurred in 28.6%, 38.4% and 42.4% of participants on the three doses, versus 14.8% on placebo, and vomiting in 10.6%, 22.8% and 25.3%, versus 4.8%. Dysesthesia, an abnormal skin sensation, was reported in 5.1%, 12.3% and 12.5% of retatrutide participants versus 0.9% on placebo; the company said these events were generally mild to moderate and most resolved during treatment.

Discontinuation due to adverse events was 4.1%, 6.9% and 11.3% on the 4 mg, 9 mg and 12 mg doses, compared with 4.9% on placebo.

What comes next

Lilly said additional TRIUMPH-1 results will be presented at the American Diabetes Association's 86th Scientific Sessions. Results from TRIUMPH-1's two basket trials, in knee osteoarthritis pain and obstructive sleep apnea, will be released later, as will data from TRIUMPH-2 in people with type 2 diabetes and TRIUMPH-3 in people with established cardiovascular disease.

Retatrutide is not approved by the FDA or any other regulator and is available only to participants in Lilly's clinical trials, the company said.