Kenneth Custer, president of Lilly Cardiometabolic, said retatrutide could, if approved, “shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions.”
That claim rests on an 80-week head-to-head trial in which Eli Lilly’s experimental weekly injection produced larger reductions in blood sugar and weight than Novo Nordisk’s highest approved Ozempic dose. Lilly announced the TRANSCEND-T2D-2 results on 28 October 2026, describing it as the first clinical trial to directly compare retatrutide with Ozempic in adults with type 2 diabetes.
The trial enrolled 1,298 adults whose diabetes was not controlled by metformin, with or without an SGLT2 inhibitor. They were assigned in a 2:2:1 ratio to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg.
After 80 weeks, the 12 mg retatrutide group had reduced A1c by 2.2 percentage points, compared with a 1.8 percentage-point reduction in the Ozempic 2 mg group. Lilly said the 12 mg dose met the trial’s primary objective, which was to show it was noninferior to Ozempic on A1C reduction.
Lilly said retatrutide also produced greater A1c reductions than Ozempic at the 9 mg dose, where the advantage reached nominal statistical significance.
The larger difference came in weight loss. Participants receiving retatrutide 12 mg lost an average of 47.4 pounds (20.9%) after 80 weeks, against 20.9 pounds (9.4%) for those on Ozempic 2 mg.
Those receiving retatrutide 9 mg lost an average of 44.3 pounds (19.5%).
The weight-loss estimates require some caution. They came from analyses of participants who remained on treatment, rather than all those enrolled in the trial.
Lilly also said retatrutide delivered greater improvements than Ozempic in non-HDL cholesterol, triglycerides and systolic blood pressure.
Retatrutide is a once-weekly injection that activates receptors for GIP, GLP-1 and glucagon. Ozempic mimics GLP-1 alone.
The safety results pointed in the other direction. Adverse events led 4.8% of participants on retatrutide 9 mg and 7.9% on retatrutide 12 mg to discontinue treatment, compared with 2.7% on Ozempic.
Diarrhea affected 28.3% of people on retatrutide 9 mg, 32.7% on retatrutide 12 mg and 26.4% on Ozempic. Nausea affected 21.2%, 23.8% and 21.3% of those groups respectively.
Ambre James-Brown, Novo’s head of global media, said Ozempic should be assessed on more than weight loss and pointed to positive effects at its top doses on cardiac, renal and hepatic health.
Lilly said this was the sixth Phase 3 trial in which retatrutide had shown strong efficacy. It is also comparing retatrutide with tirzepatide, the active compound in Zepbound, in another late-stage study involving adults with obesity.
The company said retatrutide has not been approved by the Food and Drug Administration or any regulatory organisation anywhere in the world. Lilly expects to submit it to the Food and Drug Administration in early 2027, with potential availability sometime in 2027 for type 2 diabetes, obesity, obesity-related sleep apnea and knee osteoarthritis.
The results have yet to be peer-reviewed or published in a medical journal. Lilly released them as it prepared to announce its quarterly earnings on Thursday.
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