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# Lilly’s Triple-Agonist Cuts Weight by Nearly 29%
- URL: https://www.fdaweb.com/lillys-triple-agonist-cuts-weight-by-nearly-29/
- Published: 2025-12-11T12:00:00.000Z
- Updated: 2026-09-14T15:29:02.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5160370

Eli Lilly’s investigational triple-agonist retatrutide produced substantial weight loss and meaningful reductions in knee osteoarthritis pain in a pivotal Phase 3 trial, positioning the once-weekly injectable as a potential next-generation therapy for obesity complicated by musculoskeletal disease, according to the company.

In the 445-patient TRIUMPH-4 study, adults with obesity or overweight and knee osteoarthritis who received the highest 12 mg dose of retatrutide lost an average of 28.7% of their body weight — about 71 pounds — after 68 weeks, Lilly says. Participants on the 9 mg dose lost 26.4%, compared with just 2.1% on placebo. Eighty-four percent of participants entered the trial with a BMI of 35 or higher.

The drug, which simultaneously activates the GIP, GLP-1, and glucagon receptors, also delivered marked improvements in joint pain and function, according to the company. On the Western Ontario and McMaster Universities Osteoarthritis Index pain scale, retatrutide lowered pain scores by up to 4.5 points, a 75.8% reduction from baseline. Physical function scores improved to a similar degree. A post-hoc analysis found that more than one in eight retatrutide-treated participants reported being completely free of knee pain at week 68, versus about one in 25 in the placebo group, Lilly adds.

The safety profile resembled that of other incretin-based agents, with gastrointestinal symptoms the most common adverse events reported, Lilly says. Nausea affected up to 43% of retatrutide recipients, diarrhea up to 35%, constipation up to 25%, and vomiting about 21%. Most events were mild, it says, and overall discontinuation rates were similar between active drug and placebo. Higher discontinuation rates at the 12 mg dose were closely tied to higher baseline body mass index, it adds.

Lilly plans to present full study data at a future medical meeting and publish the results in a peer-reviewed journal. Seven additional Phase 3 trials evaluating retatrutide in obesity, Type 2 diabetes, osteoarthritis, sleep apnea, and other cardiometabolic and musculoskeletal conditions are expected to read out in 2026.