Lilly's Retatrutide Cuts Body Weight Up to 20.9%, Beating Ozempic

Eli Lilly said on Oct. 28 that its experimental drug retatrutide beat Novo Nordisk's Ozempic in a phase 3 trial in type 2 diabetes. It lowered blood sugar more and led to more than twice the weight loss. The Indianapolis company compared two retatrutide doses with Ozempic 2 mg, the highest approved dose.

What happened

The trial, called TRANSCEND-T2D-2, enrolled 1,298 adults whose diabetes was not well controlled on metformin, with or without an SGLT2 inhibitor. It was randomized and open label. People received retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg and were followed for 80 weeks.

Lilly reported these results at 80 weeks using its efficacy estimand:

• Blood sugar: From an average A1C of 8.3%, both retatrutide doses lowered A1C by 2.2%. Ozempic lowered it by 1.8%.
• Weight: From an average starting weight of 102.4 kg, people lost 19.5% on the 9 mg dose and 20.9% on the 12 mg dose. People on Ozempic lost 9.4%.
• In kilograms: That was 20.1 kg and 21.5 kg with retatrutide, compared with 9.5 kg with Ozempic.

Lilly said retatrutide also did better than Ozempic on non-HDL cholesterol, triglycerides and systolic blood pressure.

The most common side effects included diarrhea, nausea, constipation, vomiting and dyspepsia. Diarrhea was reported in 28.3% and 32.7% of people on the two retatrutide doses, and in 26.4% on Ozempic. Dysesthesia occurred in 4.8% and 6.5% on retatrutide and 2.7% on Ozempic. Side effects led 4.8% and 7.9% of retatrutide patients to stop treatment, compared with 2.7% on Ozempic. Lilly said most events were mild to moderate.

Why it matters

Retatrutide is a once weekly drug that acts on three hormone receptors: GLP-1, GIP and glucagon. That is why it is nicknamed a triple G drug. Reuters reported that triple G drugs are expected to produce more weight loss than earlier drugs in the class.

The trial pits Lilly's next drug directly against a leading Novo Nordisk product. Kenneth Custer, who leads Lilly Cardiometabolic Health, said retatrutide, if approved, "could shift the treatment paradigm" for people with type 2 diabetes, obesity and related conditions.

The results come from a company press release. Full data have not yet been presented or peer reviewed. Retatrutide is not approved by the FDA or any other regulator.

What it means for people in the industry

Lilly said detailed results will go to a medical meeting and a peer reviewed journal. About 650 participants are continuing on retatrutide for 24 more weeks in an extension. The company is also running TRIUMPH-5, a phase 3 trial comparing retatrutide with tirzepatide in adults with obesity.

Medical affairs, market access and clinical teams should watch for the full data and for regulatory filing plans. This article is news, not medical advice.

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Sources

• Lilly's retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic's highest approved dose in head-to-head trial, Eli Lilly
• Lilly's next-gen drug outshines Ozempic on weight loss, blood sugar control in trial, Reuters (via SRN News)