Retatrutide Reduced Sleep Apnea Severity vs Placebo in Phase 3 TRIUMPH-OSA Trials

Once-weekly retatrutide led to significantly greater reductions in the apnea-hypopnea index (AHI) than placebo in adults with obstructive sleep apnea (OSA) and obesity or overweight, with or without type 2 diabetes, according to two phase 3 trials published in NEJM.

Retatrutide is an investigational triple agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. The double-blind, randomized, placebo-controlled TRIUMPH-1-OSA and TRIUMPH-2-OSA trials, nested within larger basket trials, enrolled adults with moderate-to-severe OSA and a body mass index of at least 27kg/m² without or with type 2 diabetes, respectively. Participants received subcutaneous retatrutide 4mg, 9mg, or 12mg or placebo.

The primary end point was the change in AHI at 80 weeks with the 9mg and 12mg doses. The trials randomized 243 and 448 participants, with baseline mean AHI values of 58.6 and 55.9 events per hour, respectively. Using a hybrid-treatment estimand, AHI in TRIUMPH-1-OSA decreased by 34.3 and 31.7 events per hour with 9mg and 12mg vs 9.9 with placebo (difference with 9mg, −24.4 events per hour; 95% CI, −34.1 to −14.7). In TRIUMPH-2-OSA, AHI decreased by 24.7 and 25.4 events per hour with 9mg and 12mg vs 10.3 with placebo, corresponding to placebo-adjusted reductions of 14.4 and 15.1 events per hour. Intention-to-treat analyses yielded differences of similar magnitude.

Smaller AHI reductions occurred with 4mg than with the higher doses, and the 4mg dose was not included in the primary end point. For the key secondary end point, mean body weight change with retatrutide ranged from −12.5% to −22.2% in TRIUMPH-1-OSA and from −12.1% to −18.5% in TRIUMPH-2-OSA, vs −4.8% and −5.6% with placebo, respectively. Gastrointestinal events were the most common adverse events.

The investigators concluded that retatrutide resulted in significantly greater AHI decreases than placebo in this population. Results were presented at the 28th Congress of the European Sleep Research Society.

Source: Grunstein RR, Somers VK, Azarbarzin A, et al. Retatrutide once weekly for treatment of obstructive sleep apnea. N Engl J Med. Published online October 20, 2026. doi:10.1056/NEJMoa2611477