Lilly says retatrutide beats Ozempic in diabetes trial

Eli Lilly's experimental drug retatrutide lowered blood sugar more than Novo Nordisk's ↗ 0.02% Ozempic and produced more than twice the weight loss in a Phase 3 trial of adults with type 2 diabetes, Lilly announced Wednesday. Lilly called the study, TRANSCEND-T2D-2, the first Phase 3 trial to compare retatrutide with another incretin medicine. The data give doctors a direct comparison as Lilly prepares to seek regulatory approval, BioSpace reported.investor.lilly.com+1

Blood sugar and weight results

After 80 weeks, both the 9 mg and 12 mg doses of retatrutide cut A1C by an average of 2.2%, compared with 1.8% for Ozempic 2 mg, the highest approved dose. Patients started at an average A1C of 8.3%, according to Lilly. Patients on retatrutide lost an average of 44.3 pounds (19.5%) on the lower dose and 47.4 pounds (20.9%) on the higher dose, while the Ozempic group lost 20.9 pounds (9.4%). Lilly said the drug met its primary goal and all key secondary goals. It also reported larger improvements in non-HDL cholesterol, triglycerides and systolic blood pressure.investor.lilly.com

STAT noted that this much weight loss stands out because people with diabetes usually lose less weight on these drugs. It also pointed out that the figures come from analyses of participants who stayed on treatment. The open-label study enrolled 1,298 adults whose diabetes was not well controlled on metformin, with or without an SGLT2 inhibitor.statnews.com

Higher side-effect rates

The extra benefit came with more side effects. Diarrhea affected 28.3% and 32.7% of patients on the two retatrutide doses, compared with 26.4% on Ozempic. Dysesthesia, a prickling or burning sensation, occurred in 4.8% and 6.5% of retatrutide patients versus 2.7% on Ozempic, Lilly said. Discontinuation due to adverse events was 4.8% and 7.9% on retatrutide, compared with 2.7% on Ozempic. Constipation was less common on retatrutide, at up to 14.2% versus 19.8% for Ozempic, Fierce Biotech reported.fiercebiotech.com+1

Path to approval

Retatrutide is a once-weekly shot that activates three hormone receptors, GIP, GLP-1 and glucagon. Lilly said this is the sixth Phase 3 trial in which the drug has delivered strong results, and the company is also testing it head-to-head against its own tirzepatide in TRIUMPH-5. Lilly plans to file for FDA approval in the first quarter of 2027. Detailed results will be presented at a future medical meeting.fiercebiotech.com

"We believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions," said Kenneth Custer, president of Lilly Cardiometabolic Health, in the company's release.investor.lilly.com