Lilly's retatrutide shows significantly greater weight loss than Ozempic, Wegovy in 15-month obesity trial
In a Phase 3 study, retatrutide produced about 29% body weight loss at a 12 mg dose, surpassing rivals Zepbound and Wegovy/Ozempic; safety signals and pricing remain under review.
A new obesity drug from Eli Lilly, retatrutide, showed significantly greater weight loss than Ozempic and Wegovy in a 15-month Phase 3 trial, according to Lilly on Thursday. The company said the drug produced notable weight reductions in adults with obesity and knee arthritis, a condition often linked to weight and aging, compared with placebo.
More than 400 participants with obesity and knee arthritis were randomized to receive two doses of retatrutide (9 mg or 12 mg) twice weekly or a placebo. The trial did not report results related to diabetes at this stage, and Lilly has not yet published full peer‑reviewed results. Participants began the study with a baseline body mass index of about 35.
By the end of the 15‑month period, those taking the 12‑milligram dose lost an average of 29 percent of their body weight, roughly 71 pounds. That level of weight loss was about 32 percent greater than the average for Zepbound and 64 percent greater than Wegovy and Ozempic in the same timeframe. In addition, nearly one in four participants on the 12‑mg dose achieved more than a one‑third reduction in body weight.
Participants also reported improvements in knee pain and physical function. On a zero-to‑ten knee pain scale, the highest retatrutide dose produced a 4.4‑point average reduction, compared with a 2.4‑point drop for placebo. The retatrutide group saw a 74 percent reduction in pain, versus 40 percent for placebo. Measures of physical function, assessing stiffness and mobility, fell by 4.2 points (a 72 percent improvement) compared with a 2.1‑point change (a 36 percent improvement) for placebo.
As with other GLP‑1 class therapies, the most common side effects included nausea, diarrhea, constipation and vomiting, which tended to lessen over time. Dysesthesia, a painful tingling or burning sensation, occurred in about 20 percent of participants on the higher dose and about 9 percent on the lower dose. Lilly noted that roughly 12 percent of retatrutide participants stopped taking the drug due to adverse effects, including perceived excessive weight loss, compared with about 5 percent on placebo.
Lilly has not set a price for retatrutide, saying price discussions will occur after potential regulatory approval. The company also said it will file for FDA approval following the completion of seven additional studies in people with obesity and diabetes, with results expected next year. The full set of trial findings has not yet been published in a peer‑reviewed journal.
Unlike Ozempic and Wegovy, retatrutide targets three hormones involved in appetite and metabolism: GLP‑1, GIP and glucagon. Zepbound already targets GLP‑1 and GIP, but no marketed weight‑loss therapy currently acts on glucagon. Eli Lilly has described retatrutide as a multi‑hormone medicine developed for obesity and diabetes, with the triple‑hormone approach intended to enhance weight loss and improve related symptoms.
The findings come amid rising concern about obesity in the United States. A majority of American adults are overweight or obese, with about 40 percent categorized as obese. The trial's initial findings were published in Diabetes, Obesity and Metabolism, and represent early data from a larger program that Lilly hopes will support regulatory filings in the future.