Lilly’s retatrutide outperforms Ozempic 2 mg in A1C and weight loss in Phase 3 head‑to‑head

Topline efficacy

In TRANSCEND‑T2D‑2 at 80 weeks both retatrutide doses lowered A1C by 2.2% compared with 1.8% for Ozempic 2 mg. Mean bodyweight change was −19.5% (−44.3 lbs) for retatrutide 9 mg and −20.9% (−47.4 lbs) for 12 mg versus −9.4% (−20.9 lbs) with Ozempic. Retatrutide also produced greater improvements in certain cardiovascular risk factors, including non‑HDL cholesterol, triglycerides and systolic blood pressure.

Safety

The most common adverse events with retatrutide were gastrointestinal—diarrhea, nausea, constipation and vomiting. Reported incidence (9 mg, 12 mg vs. Ozempic) included diarrhea 28.3%, 32.7% vs. 26.4% and nausea 21.2%, 23.8% vs. 21.3%. Treatment discontinuation due to adverse events was 4.8% (9 mg) and 7.9% (12 mg) versus 2.7% with Ozempic; most events were mild‑to‑moderate and typically resolved during treatment.

Trial design and context

TRANSCEND‑T2D‑2 is a Phase 3, randomized, open‑label trial (N=1,298) in adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor. Participants with baseline A1C 7.0%–10.5% were randomized 2:2:1 to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg. Retatrutide was dosed once weekly, initiated at 2 mg and increased every four weeks to the target dose. The primary objective was to demonstrate noninferiority of retatrutide 12 mg versus Ozempic 2 mg for A1C reduction at 80 weeks; an extension will continue treatment in ~650 participants for an additional 24 weeks.

Next steps and status

Detailed results will be presented at a medical meeting and submitted for peer‑review publication. Retatrutide is investigational and has not been approved by regulatory authorities for sale or marketing.