Dedicated NEJM Paper Publishes Full Phase 3 Results of Retatrutide for Sleep Apnea, Including First TRIUMPH-2-OSA Data

The New England Journal of Medicine published a paper online on October 21, 2026 titled "Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea," the first standalone, full peer-reviewed report dedicated to the obstructive sleep apnea (OSA) component of Eli Lilly's Phase 3 TRIUMPH program for its investigational triple hormone receptor agonist retatrutide. The paper, led by Ronald R. Grunstein of the Woolcock Institute of Medical Research and the TRIUMPH-1-OSA and TRIUMPH-2-OSA Investigators, combines results from two separate randomized, double-blind, placebo-controlled Phase 3 trials nested within the larger TRIUMPH-1 and TRIUMPH-2 basket trials.

TRIUMPH-1-OSA enrolled 243 adults with moderate-to-severe OSA and a body-mass index of at least 27 who did not have type 2 diabetes, nested within TRIUMPH-1 (ClinicalTrials.gov identifier NCT05929066). TRIUMPH-2-OSA enrolled 448 adults with the same OSA and weight criteria who did have type 2 diabetes, nested within TRIUMPH-2 (ClinicalTrials.gov identifier NCT05929079). Participants in both trials were randomized to once-weekly subcutaneous retatrutide at 4 mg, 9 mg or 12 mg, or to placebo. At baseline, the average apnea-hypopnea index (AHI, the number of breathing interruptions per hour of sleep) was 58.6 events per hour in TRIUMPH-1-OSA and 55.9 events per hour in TRIUMPH-2-OSA, and average body weight was 119.6 kg and 115.9 kg, respectively.

The primary endpoint in both trials was the change in AHI at 80 weeks with the 9 mg and 12 mg doses. Using a hybrid-treatment estimand, which applies a hypothetical no-treatment-failure assumption to participants who had intercurrent events suggesting treatment failure and a treatment-policy approach elsewhere, AHI fell by 22.9 (4 mg), 34.3 (9 mg) and 31.7 (12 mg) events per hour with retatrutide in TRIUMPH-1-OSA, compared with 9.9 events per hour on placebo, a difference versus placebo of 24.4 events per hour at 9 mg and 21.9 events per hour at 12 mg (95% confidence intervals -34.1 to -14.7 and -32.2 to -11.5, respectively). In TRIUMPH-2-OSA, AHI fell by 19.2 (4 mg), 24.7 (9 mg) and 25.4 (12 mg) events per hour with retatrutide, compared with 10.3 events per hour on placebo, a difference versus placebo of 14.4 events per hour at 9 mg and 15.1 events per hour at 12 mg (95% CI -21.6 to -7.2 and -22.5 to -7.7, respectively). Using an intention-to-treat estimand, the results were similar in both trials.

The TRIUMPH-2-OSA results are the first full publication of sleep apnea data from the TRIUMPH-2 program, which separately reported its main weight-loss and A1C results in a Lancet paper published September 29, 2026. That earlier Lancet publication, covering the overall TRIUMPH-2 trial in adults with type 2 diabetes and obesity or overweight, stated that results from the nested OSA sub-study would be "presented at a future medical meeting and published separately." The October 21 NEJM paper is that publication, and it is the first time TRIUMPH-2-OSA's AHI results, drawn from the 448-participant cohort with type 2 diabetes, have appeared in a peer-reviewed journal.

Body weight, a key secondary endpoint in both OSA trials, fell by 12.5% to 22.2% across the three retatrutide doses in TRIUMPH-1-OSA and by 12.1% to 18.5% in TRIUMPH-2-OSA, under a treatment-regimen estimand, compared with 4.8% and 5.6% on placebo in the respective trials. The authors reported that the most common adverse events with retatrutide in both trials were gastrointestinal, consistent with adverse-event patterns reported in Lilly's earlier TRIUMPH-1 and TRIUMPH-2 publications. The paper concludes that in adults with OSA and obesity or overweight, with or without type 2 diabetes, retatrutide produced significantly greater reductions in AHI than placebo.

Retatrutide remains investigational and has not been approved by the FDA, the European Medicines Agency, Australia's Therapeutic Goods Administration or any other regulator. The study was funded by Eli Lilly, and several authors are Lilly employees. This report describes clinical trial results and is not treatment or dosing guidance.