Lilly's retatrutide achieves 30% weight loss

Eli Lilly said on May 21 that its experimental obesity drug retatrutide met the primary and key secondary endpoints in the Phase 3 TRIUMPH-1 trial, extending the company’s push beyond Zepbound into a newer generation of weight-loss medicines. Lilly said adults with obesity or overweight plus at least one weight-related condition, but without diabetes, lost an average of 28.3% of body weight on the highest dose after 80 weeks. In a pre-specified extension among participants with a baseline body mass index of at least 35, the company said average weight loss reached 30.3% at 104 weeks. The results came from topline data and have not yet been fully presented in a peer-reviewed publication. ### How big was the weight loss in the main trial? Lilly said 2,339 participants were enrolled in the randomized, double-blind, placebo-controlled TRIUMPH-1 study. At 80 weeks, the company said patients taking retatrutide lost an average of 19.0% of body weight on 4 mg, 25.9% on 9 mg and 28.3% on 12 mg. Lilly said placebo-treated participants lost 2.1% on average. (investor.lilly.com) The 12 mg group lost an average of 70.3 pounds, Lilly said, and 45.3% of participants on that dose achieved at least 30% weight loss. CNBC, citing the company’s release and interview, reported that Lilly’s chief scientific officer Dan Skovronsky called that level of reduction an “incredible number to see.” (investor.lilly.com) ### Where does the 30.3% figure come from? Lilly said the 30.3% figure came from a pre-specified blinded extension in participants whose baseline BMI was 35 or higher. In that subgroup, people who continued on retatrutide 12 mg to 104 weeks lost an average of 85.0 pounds, according to the company. (investor.lilly.com) AJMC reported the extension result as the top-line figure from TRIUMPH-1, while Lilly’s release framed 28.3% at 80 weeks as the main Phase 3 outcome and 30.3% at 104 weeks as an extension finding in severe obesity. Those are different measurements from different timepoints in the same program, not competing numbers. (investor.lilly.com) ### What kind of drug is retatrutide? Lilly said retatrutide is an investigational, first-in-class triple hormone receptor agonist targeting GIP, GLP-1 and glucagon. That distinguishes it from currently marketed obesity drugs that target fewer pathways, including Lilly’s tirzepatide and Novo Nordisk’s semaglutide-based products. (investor.lilly.com) Ania Jastreboff of Yale School of Medicine, the trial’s lead investigator, said in Lilly’s release that people with severe obesity on the highest dose lost “on average 30% of their body weight over two years.” She also said the treatment showed improvements in assessed cardiometabolic measures. Lilly said those measures included waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein. (investor.lilly.com) ### What did Lilly say about side effects? Lilly said the safety profile was generally consistent with incretin-based therapies, with gastrointestinal adverse events the most commonly reported. The company said nausea, vomiting, diarrhea and constipation were usually mild to moderate in severity and occurred mainly during dose escalation. (investor.lilly.com) CNBC reported that a lower dose tested in TRIUMPH-1 was associated with fewer discontinuations due to side effects. Lilly’s release said the 4 mg dose, reached with a single escalation step, had a lower observed discontinuation rate due to adverse events than the higher doses. (investor.lilly.com) ### What comes next for the program? Lilly said detailed TRIUMPH-1 results will be presented at a medical meeting and published in a peer-reviewed journal. The company has been running a broader late-stage retatrutide program, including TRIUMPH-4 in obesity with knee osteoarthritis and TRANSCEND-T2D-1 in type 2 diabetes. (investor.lilly.com) May 21 was the date of Lilly’s topline disclosure, and the next public milestone is the full data presentation the company said it plans to make at a scientific meeting. Lilly has not yet announced in the release a regulatory filing date for retatrutide. (investor.lilly.com)