Eli Lilly and Company (NYSE: LLY) reported full detailed Phase III data at the ADA 2026 meeting suggesting the triple agonist retatrutide may become a multi-indication cardiometabolic franchise, demonstrating substantial benefits across obesity, diabetes, sleep apnea, and osteoarthritis. The presentation represents a follow up to a May data release showing the investigational GIP, GLP-1, and glucagon triple hormone receptor agonist produced a mean body weight reduction of 28.3% at 80 weeks in adults with obesity. In addition, retratrutide showed statistically significant improvements in knee osteoarthritis pain, obstructive sleep apnea, and glycemic control, with a regulatory submission now appearing imminent.
Trial data
TRIUMPH-1 is a Phase III, 80-week, randomized, double-blind, placebo-controlled master trial that enrolled 2,339 adults with obesity or overweight across three dose arms (4 mg, 9 mg, 12 mg) and two nested basket trials for knee osteoarthritis pain and moderate-to-severe obstructive sleep apnea. At the primary endpoint, participants achieved 28.3% weight loss versus 2.2% on placebo. In the pre-specified 104-week extension, participants with baseline BMI ≥35 continuing on 12 mg lost a mean of 30.3%, with no evidence of a plateau. On the osteoarthritis basket, retatrutide reduced WOMAC pain scores by up to 4.3 points (73.1%) from a baseline of 6.0; on the sleep apnea basket, the apnea-hypopnea index fell by up to 36.1 events per hour (60.6%) from a baseline of 58.6 events per hour.
In TRANSCEND-T2D-1, a Phase III, 40-week, placebo-controlled trial in 537 adults with early type 2 diabetes (mean duration 2.5 years, baseline A1C 7.9%), retatrutide reduced A1C by up to 2.0% — with up to 90% of participants achieving the ADA's general target of below 7.0% and 46% reaching normoglycemia below 5.7%. Participants on 12 mg also lost a mean of 36.6 lbs (16.8%), with weight loss not plateauing at 40 weeks. TRANSCEND-T2D-1 results were simultaneously published in The Lancet. Adverse events across both trials were consistent with the incretin class — predominantly gastrointestinal and dose-dependent — with discontinuation rates of 11.3% at the 12 mg dose in TRIUMPH-1. A dysesthesia signal, occurring in approximately 12.5% of participants on 12 mg versus 0.9% on placebo, was reported as generally mild and largely self-resolving, though it warrants continued monitoring given it is not a recognized class effect.