Retatrutide Meets Phase 3 Endpoints in TRANSCEND-T2D-2, the First Head-to-Head Trial Against Ozempic in Type 2 Diabetes
Eli Lilly announced topline results on October 28, 2026, from TRANSCEND-T2D-2, a Phase 3 trial of its investigational peptide retatrutide in adults with type 2 diabetes. Retatrutide is an agonist of three receptors: GIP, GLP-1, and glucagon. AJMC reported that TRANSCEND-T2D-2 is the first Phase 3 trial to compare retatrutide with another incretin-based therapy, using Ozempic (semaglutide) at its highest approved dose for type 2 diabetes as the comparator.
The randomized, open-label trial enrolled 1,298 adults whose type 2 diabetes was inadequately controlled on metformin, with or without an SGLT2 inhibitor, with a baseline HbA1c of 7.0 percent to 10.5 percent and a mean baseline of 8.3 percent. Participants were assigned to one of two retatrutide arms or to the Ozempic arm, and results were reported at 80 weeks on the efficacy estimand, which assumes participants remained on treatment without starting additional glucose-lowering medication.
Lilly reported that the trial met its primary endpoint, noninferiority on HbA1c reduction for the higher retatrutide arm against Ozempic, with superiority also shown, and met its key secondary endpoints. Both retatrutide arms lowered HbA1c by an average of 2.2 percentage points, compared with 1.8 percentage points for Ozempic. Average body weight fell by 19.5 percent and 20.9 percent in the retatrutide arms, compared with 9.4 percent in the Ozempic arm, and Lilly reported greater improvements in non-HDL cholesterol, triglycerides, and systolic blood pressure without reporting the size of those differences.
On safety, AJMC and MedCity News reported that gastrointestinal events were the most common adverse events in all arms and were mostly mild to moderate, and that discontinuation due to adverse events was higher in the retatrutide arms, at 4.8 percent and 7.9 percent, than in the Ozempic arm, at 2.7 percent. These are topline results from a company announcement. Detailed results are to be presented at a future medical meeting and published in a peer-reviewed journal.
Retatrutide is investigational and is not approved anywhere, including by the FDA. This readout changes no approval status for any product. Ozempic remains an FDA-approved semaglutide product with its own label, and any future retatrutide approval would apply only to a specific product and labeled indication decided through the FDA review process.