Eli Lilly and Company (NYSE:LLY) announced on October 28, 2026 positive topline results from TRANSCEND-T2D-2, a Phase 3 head-to-head trial in which retatrutide demonstrated greater A1C reduction and substantially more weight loss than injectable Ozempic 2 mg in adults with type 2 diabetes at 80 weeks.

Key Highlights

  • A1C reduction: Both doses of retatrutide lowered A1C by an average of 2.2% versus 1.8% with Ozempic 2 mg at 80 weeks, from an average baseline of 8.3%.
  • Weight loss: Participants on retatrutide 9 mg lost an average of 44.3 lbs (19.5%) and those on 12 mg lost 47.4 lbs (20.9%), compared to 20.9 lbs (9.4%) with Ozempic 2 mg.
  • Trial size: TRANSCEND-T2D-2 (NCT06260722) enrolled 1,298 adults with type 2 diabetes inadequately controlled with metformin, with or without an SGLT2 inhibitor.
  • Primary endpoint met: The trial's primary objective was to demonstrate noninferiority of retatrutide 12 mg versus Ozempic 2 mg in A1C reduction; retatrutide also demonstrated superiority on key secondary endpoints.
  • Adverse events: Treatment discontinuation rates due to adverse events were 4.8% (9 mg) and 7.9% (12 mg) for retatrutide versus 2.7% for Ozempic; most events were described as mild-to-moderate.
  • Regulatory status: Retatrutide remains investigational and has not been approved by the FDA or any regulatory organization.

TRANSCEND-T2D-2 Results: Retatrutide vs. Ozempic at 80 Weeks

According to Lilly's announcement, TRANSCEND-T2D-2 was a Phase 3, randomized, open-label trial that compared once-weekly retatrutide at 9 mg and 12 mg against once-weekly Ozempic 2 mg. The 1,298 participants, who had a baseline A1C of 7.0% to 10.5%, were randomized in a 2:2:1 ratio. Retatrutide was initiated at 2 mg and increased every four weeks to the target dose. The company disclosed that all comparisons of retatrutide versus Ozempic 2 mg were controlled for family-wise type 1 error, except for certain prespecified secondary endpoints that showed nominal statistical significance.

The filing states that retatrutide also delivered greater improvements than Ozempic across certain cardiovascular risk factors, including non-HDL cholesterol, triglycerides, and systolic blood pressure. The most common adverse events with retatrutide (9 mg and 12 mg versus Ozempic) were diarrhea (28.3%, 32.7% vs. 26.4%), nausea (21.2%, 23.8% vs. 21.3%), constipation (14.2%, 13.1% vs. 19.8%), vomiting (10.2%, 15.0% vs. 13.2%), and dyspepsia (10.4%, 8.5% vs. 11.6%). The incidence of dysesthesia with retatrutide (9 mg, 12 mg vs. Ozempic) was reported as 4.8%, 6.5% vs. 2.7%.

Lilly described retatrutide as an investigational, once-weekly, triple hormone receptor agonist that activates receptors for GIP, GLP-1, and glucagon. The company disclosed that TRANSCEND-T2D-2 is the sixth Phase 3 trial in which retatrutide has delivered results, and noted that detailed data will be presented at a future medical meeting and published in a peer-reviewed journal. The TRANSCEND-T2D program, which began in 2024, has enrolled more than 2,050 participants across three global registrational trials.

What Was Disclosed

Lilly disclosed topline Phase 3 efficacy and safety data from the TRANSCEND-T2D-2 trial, showing retatrutide met its primary and all key secondary endpoints versus Ozempic 2 mg at 80 weeks. Retatrutide remains an investigational molecule without regulatory approval.