Eli Lilly and Company has announced positive topline results from TRIUMPH-2 and TRIUMPH-3, 2 pivotal phase 3 trials evaluating retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist. In both studies, retatrutide met the primary endpoint, delivering substantial weight loss in adults with obesity and some of its most serious complications: type 2 diabetes and established cardiovascular disease.

Kenneth Custer, PhD, Executive Vice President (EVP) and President, Lilly Cardiometabolic Health, said, "Across 5 positive phase 3 studies, retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health. With the positive results from TRIUMPH-2 and TRIUMPH-3, we now have the clinical data package to support global submissions for retatrutide as a potential treatment for obesity, knee osteoarthritis pain, and obstructive sleep apnea. We look forward to working with regulators as they evaluate this first-of-its-kind medicine."

In TRIUMPH-2, all 3 studied doses of retatrutide (4 mg, 9 mg, and 12 mg) delivered substantial weight loss and improved glycemic control at 80 weeks in adults with type 2 diabetes and obesity or overweight. Participants taking retatrutide 4 mg, 9 mg, and 12 mg lost an average of 29.8 lbs (12.7 percent), 45.4 lbs (19.1 percent), and 49.6 lbs (20.8 percent), respectively, alongside A1C reductions of up to an average of 1.6 percent.

In TRIUMPH-3, both studied doses of retatrutide (9 mg and 12 mg) delivered substantial weight loss in adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. Participants lost up to an average of 55.8 lbs (22.6 percent) at 80 weeks.

In the study, Major Adverse Cardiovascular Events (MACE) occurred less frequently than anticipated in both retatrutide and placebo arms. In pre-specified analyses for time to first occurrence of MACE, there were 44 MACE-5 (all-cause death, heart attack, stroke, heart failure event, or coronary revascularisation) events observed in participants randomised to retatrutide (pooled 9 mg and 12 mg) and 52 events observed in those randomised to placebo, resulting in a hazard ratio of 0.82 (95.0 percent CI: 0.55 to 1.22). There were 27 MACE-3 (cardiovascular death, heart attack, or stroke) events in participants randomised to retatrutide and 23 in those randomised to placebo, resulting in a hazard ratio of 1.12 (95.0 percent CI: 0.64 to 1.96).

In TRIUMPH-3, retatrutide meaningfully reduced certain cardiovascular risk factors, with the highest dose delivering average reductions of 37.0 percent in triglycerides, 16.5 percent in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure, 7.5 in (19.0 cm) in waist circumference, and 51.2 percent in high-sensitivity C-Reactive Protein (hsCRP).

Detailed results from TRIUMPH-2 and TRIUMPH-3 will be presented at future medical meetings and published in peer-reviewed journals. Lilly is completing the comprehensive Chemistry, Manufacturing, and Controls (CMC) data package required for a Biologics License Application (BLA) and plans to subsequently submit retatrutide in Q1 2027 for US approval.