Lilly Reports 20.9% Weight Loss With Retatrutide in Trial Comparing the Drug With Ozempic
Key Facts
Eli Lilly announced positive results on October 28 from the Phase 3 TRANSCEND-T2D-2 trial, with average weight loss of 20.9% on the 12 mg dose of retatrutide after 80 weeks, compared with 9.4% on Ozempic at a dose of 2 mg. The company said the result represented statistically significant superiority in weight loss, with a p-value below 0.001. The comparison also included the 9 mg dose of retatrutide, which produced average weight loss of 19.5%. For blood sugar control, A1C fell by an average of 2.2% with both retatrutide doses, compared with 1.8% with Ozempic. Average A1C at the start of the trial was 8.3%.
The open-label, randomized trial compared weekly retatrutide doses of 9 and 12 mg with a weekly Ozempic dose of 2 mg. It included 1,298 adults whose diabetes was not adequately controlled with metformin, with or without an SGLT2 inhibitor. The study was designed with a primary objective of showing that the 12 mg dose of retatrutide was noninferior to Ozempic 2 mg in lowering A1C at week 80. Accordingly, the statistical superiority criterion reported in the results concerned weight loss, while the A1C criterion was noninferiority. These distinctions keep the comparison between the two different treatment outcomes clear.
Average weight loss with retatrutide 9 mg reached 44.3 pounds, or 19.5% of body weight, at week 80. The average rose to 47.4 pounds, equivalent to 20.9%, with the 12 mg dose. By comparison, average weight loss with Ozempic was 20.9 pounds, or 9.4% of body weight. The comparison therefore showed a difference in average weight lost between the retatrutide groups and the comparator group over the same treatment period. In the earlier Phase 3 TRANSCEND-T2D-1 trial, Lilly had reported weight loss of 36.6 pounds, or 16.8%, with the 12 mg dose at week 40, alongside an A1C reduction of up to 2.0%.
Alongside blood sugar and weight measures, Lilly said retatrutide produced greater improvements than Ozempic in some cardiovascular risk factors. These measures included non-HDL cholesterol, triglycerides and systolic blood pressure. The company did not provide figures for these measures in its results statement among the information available here. In terms of tolerability, rates of discontinuation due to side effects were 4.8% with the 9 mg dose and 7.9% with the 12 mg dose, compared with 2.7% with Ozempic. The rates show that discontinuation was more common in the retatrutide groups during the trial.
Retatrutide remains an investigational drug. It is a GIP, GLP-1 and glucagon receptor agonist administered once weekly in the trial. In earlier results announced by Lilly in July 2026 from the TRIUMPH-2 and TRIUMPH-3 trials, the company said it plans to submit a biologics license application to the FDA in the first quarter of 2027. In TRIUMPH-2, gastrointestinal disorders were among the most common side effects; diarrhea rates ranged from 27.4% to 33.6% across the three doses, and nausea rates from 13.7% to 28.0%. Kenneth Custer, president of Lilly’s cardiometabolic health business, said five positive Phase 3 studies make the drug a potential future tool for managing cardiometabolic health. Lilly shares closed at $1281.91 on October 27, 2026, the day before the TRANSCEND-T2D-2 results were announced.
Lilly said detailed results from the TRANSCEND-T2D-2 trial will be presented at a future medical meeting and published in a peer-reviewed journal. The study also includes an extension period in which about 650 participants will continue treatment with retatrutide for an additional 24 weeks. The period is intended to assess the treatment’s long-term efficacy and safety. The detailed published results will provide more information about the trial after the initial announcement. The company did not specify the date of the medical meeting or the publication date.