In TRIUMPH-2, participants with obesity and type 2 diabetes taking retatrutide 12 mg lost an average of 49.6 lbs (20.8%) over 80 weeks, with more than half no longer meeting the BMI criteria for obesity

Participants with a baseline BMI of 35 or higher who took retatrutide 12 mg lost up to an average of 60.8 lbs (23.4%) of their body weight

Retatrutide reduced A1C by up to an average of 1.6%, with up to 40.0% reaching an A1C of <5.7%

Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron),announced detailed results from TRIUMPH-2, a Phase 3 trial evaluating the efficacy and safety of retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, in adults with type 2 diabetes and obesity or overweight. At 80 weeks, all doses of retatrutide (4 mg, 9 mg, and 12 mg) delivered substantial weight loss and reductions in A1C.¹ Results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, and simultaneously published in The Lancet.

"The vast majority of people with type 2 diabetes are also living with obesity, and treating the two together has always been a challenge," said Juan P. Frías, M.D., Medical Director and Principal Investigator, Los Angeles Institute for Metabolic Research. "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. Results such as these may change what we set out to achieve with a single therapy for adults living with type 2 diabetes and obesity."

Participants taking retatrutide 4 mg, 9 mg, and 12 mg lost an average of 29.8 lbs (12.7%), 45.4 lbs (19.1%), and 49.6 lbs (20.8%), respectively. Among participants with a baseline BMI of 35 or higher, those taking retatrutide 12 mg lost an average of 60.8 lbs (23.4%). By the end of the study, 59.5% of participants taking retatrutide 12 mg no longer met the BMI criteria for obesity.

Beyond substantially reducing weight, retatrutide also helped participants better control their A1C. Participants taking retatrutide 9 mg and 12 mg reduced their A1C by an average of 1.6% and 1.5%, respectively, while those taking 4 mg reduced their A1C by an average of 1.4%. Notably, up to 40.0% of participants reached an A1C of <5.7%, which is considered a normal blood sugar level.

Retatrutide also meaningfully reduced certain cardiovascular risk factors, with the highest dose delivering average reductions of 39.5% in triglycerides, 19.6% in non-HDL cholesterol, 10.8 mmHg in systolic blood pressure, 6.7 in (16.9 cm) in waist circumference, and 58.3% in high-sensitivity C-reactive protein (hsCRP).

"TRIUMPH-2 shows what the next generation of cardiometabolic medicine could deliver: substantial weight loss, A1C reduction and improvements across other critical cardiovascular risk factors," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "With efficacy this powerful and consistent across our Phase 3 program, we believe retatrutide could become an important option for people living with type 2 diabetes and obesity."

In TRIUMPH-2, the most common adverse events with retatrutide (4 mg, 9 mg, 12 mg vs. placebo, respectively) 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%). Incidences of dysesthesia and urinary tract infections were 4.5%, 5.6%, 7.3% vs. 0.7% and 3.8%, 6.3%, 8.0% vs. 6.6% with retatrutide 4 mg, 9 mg, 12 mg vs. placebo, respectively. These events were generally mild to moderate, and the majority resolved during treatment. Discontinuation rates due to adverse events in TRIUMPH-2 were 3.8% (4 mg), 11.6% (9 mg), and 7.7% (12 mg) with retatrutide, compared with 4.9% for placebo.

Lilly plans to submit a Biologics License Application (BLA) in Q1 2027 to the U.S. Food and Drug Administration. Additional results from the obstructive sleep apnea trial within TRIUMPH-2 will be presented at a future medical meeting and published in a peer-reviewed journal.