Eli Lilly says retatrutide eases sleep apnea and knee pain in obesity trials

Eli Lilly pressed its next-generation obesity drug retatrutide into a broader medical debate on Saturday in New Orleans: whether one injectable medicine can do more than shrink waistlines and also blunt the diseases that often follow obesity. The company said the drug reduced moderate-to-severe sleep apnea severity and eased knee osteoarthritis pain in Phase 3 trial baskets, findings that could help reshape treatment for conditions now handled mostly with CPAP machines, pain management, and weight loss advice.

The results came from TRIUMPH-1, an 80-week Phase 3 master trial that randomized 2,339 participants 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg or placebo. Lilly built two nested basket trials into the study, one for knee osteoarthritis pain and another for moderate-to-severe obstructive sleep apnea, underscoring how tightly obesity, sleep disorders and joint disease are being studied together.

At the 12 mg dose, participants lost an average of 70.3 pounds, or 28.3%, over 80 weeks, and 65.3% fell below a body mass index of 30. In a study extension among participants with a baseline BMI of at least 35, average weight loss reached 85.0 pounds, or 30.3%, by 104 weeks. In the sleep apnea basket, retatrutide cut severity by as much as 36.1 events per hour, or 60.6%. In the knee pain basket, it reduced WOMAC knee pain by up to 4.3 points, or 73.1%.

Those findings arrive as Lilly tries to define retatrutide as more than another weight-loss drug. Ania Jastreboff of Yale School of Medicine, the lead investigator, said obesity drives more than 200 downstream diseases and that treating those conditions in silos has been a historical shortcoming. The company said retatrutide is an investigational, first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist, a mechanism that may matter for effects beyond weight loss alone.

Lilly also highlighted a separate Phase 3 diabetes study, TRANSCEND-T2D-1, which enrolled 537 adults with recent-onset type 2 diabetes, an average duration of 2.5 years, and poor control despite diet and exercise alone. The trial showed A1C reductions of up to 2.0% and average weight loss of 36.6 pounds, or 16.8%, at 40 weeks, along with better LDL cholesterol, triglycerides and blood pressure. The findings were published simultaneously in The Lancet, and Lilly said there were no new safety concerns in its summary, though one diabetes study reported major adverse cardiovascular events in 2% of patients taking the lowest dose, without establishing causation.

The broader commercial stakes are substantial. Lilly’s older drug Zepbound is already approved for sleep apnea, and rivals including Novo Nordisk are fighting for share in a market that now stretches across obesity, diabetes, sleep medicine and cardiometabolic disease. Lilly also has an event-driven cardiovascular-and-kidney outcomes trial for retatrutide expected to enroll 10,000 participants and finish in February 2029, while the company has said it intends to seek regulatory review by the end of 2026 if the phase 3 program stays on track.