Indianapolis – September 30, 2026 -- Eli Lilly and Company (NYSE: LLY) reported that its investigational triple hormone receptor agonist retatrutide produced an average weight loss of 49.6 lbs (20.8%) over 80 weeks at the 12 mg dose in patients with type 2 diabetes and obesity, with more than half of participants no longer meeting BMI criteria for obesity. The Phase 3 TRIUMPH-2 results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan and simultaneously published in The Lancet.
Highest dose delivers weight loss up to 23.4% in heavier patients
Across the three tested doses, participants lost an average of 29.8 lbs (12.7%) at 4 mg, 45.4 lbs (19.1%) at 9 mg, and 49.6 lbs (20.8%) at 12 mg. Among patients with a baseline BMI of 35 or higher, the 12 mg dose produced an average loss of 60.8 lbs (23.4%), with 59.5% of all 12 mg participants no longer classified as having obesity by trial end.
Drug lowers A1C by up to 1.6%, pushing 40% into normal blood sugar range
Retatrutide reduced A1C by an average of 1.4% (4 mg), 1.6% (9 mg), and 1.5% (12 mg). Up to 40.0% of participants reached an A1C below 5.7%, the threshold for normal blood sugar. "In TRIUMPH-2, retatrutide reduced both weight and blood sugar substantially, with more than half of participants no longer qualifying as having obesity and up to 40% reaching an A1C in the normal range," said Juan P. Frías, M.D., Medical Director and Principal Investigator at the Los Angeles Institute for Metabolic Research.
Triple hormone agonist cuts cardiovascular risk markers at highest dose
At 12 mg, retatrutide reduced triglycerides by an average of 39.5%, non-HDL cholesterol by 19.6%, systolic blood pressure by 10.8 mmHg, waist circumference by 6.7 in (16.9 cm), and high-sensitivity C-reactive protein by 58.3%.
Gastrointestinal side effects climb with dose, discontinuation reaches 11.6%
The most common adverse events at 4 mg, 9 mg, and 12 mg versus placebo were diarrhea (27.4%, 33.5%, 33.6% vs. 13.2%), nausea (13.7%, 20.8%, 28.0% vs. 8.0%), constipation (14.0%, 16.2%, 16.8% vs. 9.4%), decreased appetite (5.8%, 12.3%, 17.1% vs. 4.5%), and vomiting (5.5%, 10.2%, 15.7% vs. 4.2%). Discontinuation rates due to adverse events were 3.8% (4 mg), 11.6% (9 mg), and 7.7% (12 mg), compared with 4.9% for placebo.
Lilly targets FDA filing in first quarter of 2027
TRIUMPH-2 randomized 1,152 participants in a 1:1:1:1 ratio to retatrutide 4 mg, 9 mg, 12 mg, or placebo, with doses titrated stepwise over 80 weeks. Lilly plans to submit a Biologics License Application to the U.S. Food and Drug Administration in the first quarter of 2027. The broader TRIUMPH Phase 3 program, launched in 2023, has enrolled more than 5,800 participants across four global registrational trials covering obesity, type 2 diabetes, obstructive sleep apnea, and knee osteoarthritis pain.