Retatrutide more than doubled Ozempic's weight loss in a head-to-head phase 3 trial in type 2 diabetes
Adults with type 2 diabetes in a phase 3 human trial (topline results from the company).
In TRANSCEND-T2D-2, 1,298 adults with type 2 diabetes lost 19.5% to 20.9% of body weight on retatrutide over 80 weeks, against 9.4% on Ozempic's highest dose, with a bigger drop in A1C.
What happened
Eli Lilly announced topline results from TRANSCEND-T2D-2 on 28 October 2026. It is the first phase 3 trial to put retatrutide head to head against another incretin drug: Ozempic (semaglutide) at 2 mg, its highest approved dose for type 2 diabetes.
The trial enrolled 1,298 adults whose type 2 diabetes was not controlled on metformin, with or without an SGLT2 inhibitor. They were randomized to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg once a week, and followed for 80 weeks. The trial was open-label, so participants knew which drug they were on.
At 80 weeks, A1C fell by an average of 2.2% on both retatrutide doses, against 1.8% on Ozempic, from a starting average of 8.3%. Body weight fell 19.5% on 9 mg and 20.9% on 12 mg, against 9.4% on Ozempic. Retatrutide met the main goal and every key secondary goal, and also did better on non-HDL cholesterol, triglycerides and systolic blood pressure.
How it works
Ozempic works on one hormone receptor, GLP-1. Retatrutide is a single molecule that works on three: GLP-1, GIP and glucagon. The glucagon arm is thought to add energy use and liver fat burning on top of the appetite effect of the other two.
That extra reach is the reason Lilly ran the comparison. Weight has historically been harder to lose for people with type 2 diabetes, and the gap here is wide: more than double the weight loss at the higher dose.
Side effects
The most common side effects were digestive, as with other drugs in this class, and most were mild to moderate. Diarrhea was reported by 28.3% and 32.7% on retatrutide 9 mg and 12 mg, against 26.4% on Ozempic, and nausea by 21.2% and 23.8%, against 21.3%.
Dysesthesia, an unusual skin sensation, came up in 4.8% and 6.5%, against 2.7% on Ozempic. Stopping because of side effects happened in 4.8% and 7.9% on retatrutide, against 2.7% on Ozempic.
What's next
Lilly says the full results will be presented at a medical meeting and published in a peer-reviewed journal. A second head-to-head trial, TRIUMPH-5, is comparing retatrutide with tirzepatide in adults with obesity.
Retatrutide is still investigational. It is not approved by the FDA or any other regulator yet.
The numbers
- Phase 3 TRANSCEND-T2D-2, 1,298 adults with type 2 diabetes, 80 weeks, open-label
- Weight: -19.5% (9 mg) and -20.9% (12 mg) vs -9.4% on Ozempic 2 mg
- A1C: -2.2% on both doses vs -1.8% on Ozempic, from an average of 8.3%
- Stopped for side effects: 4.8% and 7.9% vs 2.7% on Ozempic
The original: Eli Lilly press release (TRANSCEND-T2D-2 topline)
