Eli Lilly and Co (NYSE:LLY) reported positive topline results from its Phase 3 TRIUMPH-4 trial evaluating its obesity treatment retatrutide in adults with obesity and knee osteoarthritis.
The investigational drug, a once-weekly injectable targeting GLP‑1, GIP, and glucagon receptors, is designed to regulate appetite and metabolism through multiple hormone pathways.
In the 68-week trial, participants receiving the highest dose of retatrutide lost an average of 28.7% of their body weight, equivalent to roughly 71 pounds.
Weight-loss effects remained substantial even when including all participants who discontinued treatment, averaging 23% to 24% in that analysis.
Beyond weight loss, retatrutide was associated with reductions in knee pain and improvements in physical function, according to Eli Lilly. Using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, participants reported an average pain reduction of 4.5 points, or 75.8%, and over 12% of treated participants experienced complete relief from knee pain by the end of the study.
The safety profile was generally consistent with other GLP‑1–based therapies, with gastrointestinal side effects such as nausea and vomiting among the most commonly reported adverse events. Discontinuation rates at the highest dose were 12% to 18%, compared with approximately 4% for placebo, including some participants who stopped due to rapid weight loss.
“People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement,” said Dr Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health. “We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function.”
Eli Lilly has seven additional Phase 3 trials of retatrutide underway, examining the drug’s effects in obesity, type 2 diabetes, and related conditions, with readouts expected by 2026.
Shares of Eli Lilly added 1.4% at $1,008 following the release of the data.