Lilly’s retatrutide tops Ozempic in Phase 3 diabetes trial

Eli Lilly's experimental triple-hormone drug retatrutide beat Novo Nordisk's Ozempic on weight loss and blood sugar control in the Phase 3 TRANSCEND-T2D-2 trial, the company announced on Wednesday. Lilly called the study the first Phase 3 trial to test retatrutide directly against another incretin-based medicine. The study included 1,298 adults with type 2 diabetes not adequately controlled on metformin, with or without an SGLT2 inhibitor. Lilly announced the results on October 28, 2026; detailed findings have not been peer reviewed or presented at a medical meeting.

After 80 weeks, participants on retatrutide 9 mg lost an average of 44.3 pounds, or 19.5 percent of body weight, and those on 12 mg lost 47.4 pounds, or 20.9 percent. People taking Ozempic 2 mg, the highest approved dose, lost 20.9 pounds, or 9.4 percent. Both retatrutide doses reduced A1C by 2.2 percentage points on average, compared with a 1.8-point reduction for Ozempic. According to Biopharma Dive, only the 12 mg dose showed a statistically significant A1C advantage over Ozempic; Lilly described the 9 mg difference as nominal. The company said the study met its primary endpoint and all key secondary endpoints. Lilly said it used Ozempic 2 mg because it is the highest approved Ozempic dose; Reuters called that a lower-dose version, and a Moomoo post noted Novo Nordisk sells higher semaglutide doses under the Wegovy brand.

The drug also improved several cardiovascular risk markers, including cholesterol carried in non-HDL particles, triglyceride levels, and systolic blood pressure. Retatrutide is a once-weekly investigational medicine that activates GIP, GLP-1 and glucagon receptors, a triple mechanism sometimes called triple-G. Drugs in this triple-G class are expected to achieve more weight loss than earlier generations by combining reduced appetite, blood sugar control and higher calorie burning.

Side effects were mainly gastrointestinal. Diarrhoea occurred in 28.3 percent of the 9 mg group and 32.7 percent of the 12 mg group, versus 26.4 percent for Ozempic. Nausea was reported by 21.2 percent and 23.8 percent of retatrutide patients, compared with 21.3 percent on Ozempic. Discontinuation due to adverse events was higher with retatrutide: 4.8 percent for 9 mg and 7.9 percent for 12 mg, compared with 2.7 percent for Ozempic. According to Lilly, most side effects were mild or moderate and generally went away while treatment continued.

Lilly's executive vice president and president of cardiometabolic health, Kenneth Custer, said the company believes retatrutide could change treatment approaches for type 2 diabetes, obesity and related cardiometabolic disease if regulators approve it. Retatrutide is not approved by the FDA or any regulator, and Lilly cautioned that people selling the investigational drug directly to consumers are breaking the law. The results do not show how retatrutide would perform in routine care, and its safety and efficacy still need to be established through regulatory review. Lilly is testing retatrutide in several other Phase 3 trials, including the ongoing TRIUMPH-5 study comparing it with tirzepatide. Detailed results from TRANSCEND-T2D-2 are expected at a future medical meeting and in a peer-reviewed journal.

Update, October 30, 2026

Novo Nordisk, the company that sells Ozempic, pushed back on the trial's weight-loss comparison, saying the drug should also be judged on its benefits for the heart, kidneys and liver, according to EMJ. Lilly separately said it plans to seek U.S. approval of retatrutide in 2027, EMJ reported. Lilly shares rose about 1.2% in morning trading after the announcement, while Novo's U.S.-listed shares edged lower, EMJ reported.