Eli Lilly's retatrutide tops Ozempic with 20.9% vs 9.4% weight loss in diabetes trial

Oct 28, 9:04 AM

Eli Lilly said on Oct 28 that its experimental drug retatrutide beat Novo Nordisk's Ozempic in TRANSCEND-T2D-2, a head-to-head Phase 3 trial in adults with type 2 diabetes. After 80 weeks, people on retatrutide lost more than twice as much weight as those on Ozempic 2 mg, the drug's highest approved dose, and had a larger drop in blood sugar.

Retatrutide is a once-weekly injection that targets three hormone receptors: GLP-1, GIP and glucagon. The trial enrolled 1,298 patients and is the first Phase 3 study to test retatrutide directly against another drug of its class. Retatrutide is still investigational and is not approved for sale.

The results

Lilly said retatrutide met the trial's main goal and all key secondary goals. Both doses lowered A1C, a measure of average blood sugar, by 2.2 percentage points, against 1.8 points for Ozempic. Participants started at an average A1C of 8.3% and an average weight of 225.8 pounds.

Treatment	A1C change	Weight change	Stopped over side effects
Retatrutide 9 mg	-2.2 points	-19.5% (44.3 pounds)	4.8%
Retatrutide 12 mg	-2.2 points	-20.9% (47.4 pounds)	7.9%
Ozempic 2 mg	-1.8 points	-9.4% (20.9 pounds)	2.7%

Lilly reported the figures on an efficacy basis, which STAT noted counts only participants who stayed on treatment. Retatrutide also improved some heart-risk measures more than Ozempic, including cholesterol, triglycerides and blood pressure.

Side effects

The most common side effects were digestive. Diarrhea affected 28.3% and 32.7% of patients on the 9 mg and 12 mg doses, against 26.4% on Ozempic. Nausea affected 21.2% and 23.8%, against 21.3%.

Dysesthesia, a type of abnormal sensation, occurred in 4.8% and 6.5% of retatrutide patients, against 2.7% on Ozempic. Lilly said most side effects were mild to moderate.

Who is exposed

Novo Nordisk makes Ozempic, the comparator in the trial. In premarket trading on Oct 28, Novo's US-listed shares were down 1.1% and Lilly's were down 0.4%, Stocktwits reported. Lilly's shares are up more than 18% in 2026, while Novo's are down 26%.

Lilly already sells tirzepatide as Mounjaro for diabetes and Zepbound for obesity. In the second quarter, Mounjaro sales were $9.94 billion and Zepbound sales $4.93 billion. Lilly is also testing retatrutide against tirzepatide in TRIUMPH-5, an ongoing Phase 3 trial in adults with obesity.

What comes next

Lilly reports third-quarter results on Oct 29, with a conference call at 10 a.m. ET.
Lilly plans to seek FDA approval of retatrutide for obesity in early 2027.
Detailed TRANSCEND-T2D-2 results will be presented at a future medical meeting and published in a peer-reviewed journal.