Lilly's retatrutide beat Ozempic with 20.9% weight loss

People with type 2 diabetes on the top dose of retatrutide lost 20.9% of their body weight in 80 weeks, more than twice the 9.4% on Ozempic, Eli Lilly said Oct. 28. It is the first head to head trial of Lilly’s experimental shot against Novo Nordisk’s best seller.

The trial, called TRANSCEND-T2D-2, enrolled 1,298 adults whose diabetes was not controlled on metformin, with or without an SGLT2 inhibitor. At the start they averaged 225.8 lbs, a BMI of 36.8 and an A1C of 8.3%. Patients were randomized 2:2:1 across the two retatrutide doses and Ozempic. It was open label, so patients knew which drug they got.

Why it matters: retatrutide hits three hormone receptors, GIP, GLP-1 and glucagon. Ozempic hits one. If the full data hold, Lilly will have a diabetes shot that takes off twice the weight of the market leader.

The numbers

Weight loss at 80 weeks, per Lilly:

• Retatrutide 12 mg: 47.4 lbs, or 20.9%
• Retatrutide 9 mg: 44.3 lbs, or 19.5%
• Ozempic 2 mg: 20.9 lbs, or 9.4%

Both retatrutide doses cut A1C by 2.2 points. Ozempic cut it by 1.8 points. Lilly notes the 9 mg edge on A1C is nominal only.

Retatrutide also improved non HDL cholesterol, triglycerides and systolic blood pressure more than Ozempic did, the company said.

The cost in side effects

More people quit. On retatrutide, 4.8% (9 mg) and 7.9% (12 mg) stopped because of adverse events. On Ozempic, 2.7% did.

Diarrhea hit 28.3% and 32.7% of retatrutide patients versus 26.4% on Ozempic. Nausea rates were close, at 21.2% and 23.8% versus 21.3%. Dysesthesia, an unpleasant skin sensation, showed up in 4.8% and 6.5% versus 2.7%.

Those are topline figures from a press release. Lilly says detailed results will be presented at a medical meeting and published in a journal.

Where it goes next

This is the sixth Phase 3 retatrutide trial to report positive results, per Lilly. Another, TRIUMPH-5, pits it against Lilly’s own tirzepatide and is still running.

Retatrutide is not approved anywhere. Lilly says selling it is illegal. People are buying it anyway on a black market, BioPharma Dive reports.

Leerink analyst David Risinger estimates $15 billion in retatrutide sales in 2032, against a $10 billion consensus, per BioPharma Dive. That is the same year semaglutide, the drug in Ozempic, loses US patent protection. Novo’s own triple acting candidates are still in Phase 2.

For now, the only legal way to get retatrutide is a clinical trial.