Eli Lilly and Company (NYSE: LLY) announced that its experimental drug retatrutide helped adults with type 2 diabetes lose more than twice as much weight as Novo Nordisk (NYSE: NVO)‘s Ozempic in the first Phase 3 trial to pit retatrutide against another incretin medicine.
The 80-week TRANSCEND-T2D-2 trial enrolled 1,298 adults whose blood sugar stayed too high despite metformin, taken alone or alongside an SGLT2 inhibitor. Retatrutide patients lost 19.5% of their body weight on the 9 mg dose and 20.9% on the 12 mg dose, or 44.3 lbs and 47.4 lbs.
Patients on Ozempic 2 mg, the highest approved dose, lost 9.4%, or 20.9 lbs. A1C fell 2.2 points on both retatrutide doses from an average of 8.3%, versus 1.8 points on Ozempic. Lilly said retatrutide also beat Ozempic on cholesterol, triglycerides and blood pressure but did not release those figures.
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Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, said retatrutide produced “more than double the weight loss” of Ozempic’s top dose.
Ozempic is approved for type 2 diabetes. Novo sells the same drug, semaglutide, for weight loss as Wegovy, and the trial did not test retatrutide against Wegovy in people with obesity. Lilly is running a separate head-to-head trial, TRIUMPH-5, against its own tirzepatide in that population. In placebo-controlled trials of adults without diabetes, retatrutide 12 mg produced 28.3% weight loss over 80 weeks and Wegovy produced 14.9% over 68 weeks. The populations and trial lengths differ, so the two cannot be compared directly.
The trial was open-label, so patients and doctors knew which drug each person received. Lilly sponsored the study, announced only topline figures and said it will publish detailed results in a peer-reviewed journal.
Diarrhea, the most common side effect, affected 28.3% of patients on 9 mg and 32.7% on 12 mg, against 26.4% on Ozempic, while nausea rates ran close to Ozempic’s. Dysesthesia, an abnormal skin sensation, affected 4.8% on 9 mg and 6.5% on 12 mg, versus 2.7% on Ozempic. Side effects led 4.8% of patients on 9 mg and 7.9% on 12 mg to stop treatment, compared with 2.7% on Ozempic. Lilly described most events as mild to moderate.
Retatrutide has not been approved anywhere, and Lilly says selling it to consumers is illegal. Lilly intends to file for FDA approval as a biologic in the first quarter of 2027. The FDA’s standard goal for a new biologic is 10 months after a 60-day filing period, which points to a decision around early 2028 unless the agency grants priority review. Novo expects an FDA decision on CagriSema, its combination of cagrilintide and semaglutide, by the end of the year.
