Retatrutide for Sleep Apnea: Two Phase 3 Trials in the NEJM Report Lower Apnea-Hypopnea Index Scores

Which numbers these are. Every figure below is from the paper’s published abstract (Grunstein RR, Somers VK, Azarbarzin A, Malhotra A, et al.). The full text was not read for this article, so subgroup results and the full adverse-event tables are not described here.

What the trials tested

TRIUMPH-1-OSA and TRIUMPH-2-OSA were double-blind, randomized, placebo-controlled trials nested inside two larger phase 3 basket trials of once-weekly subcutaneous retatrutide (ClinicalTrials.gov NCT05929066 and NCT05929079). They enrolled adults with moderate-to-severe obstructive sleep apnea and a body-mass index of at least 27: without type 2 diabetes in TRIUMPH-1-OSA (243 participants) and with it in TRIUMPH-2-OSA (448). Participants received retatrutide at 4 mg, 9 mg or 12 mg, or placebo.

The primary end point was the change in the apnea-hypopnea index (AHI), the average number of apneas and hypopneas per hour of sleep, at 80 weeks with the 9 mg and 12 mg doses. At baseline the mean AHI was 58.6 events per hour in TRIUMPH-1-OSA and 55.9 in TRIUMPH-2-OSA, and mean body weight was 119.6 kg and 115.9 kg.

What they reported

• TRIUMPH-1-OSA (without type 2 diabetes). Mean AHI change at 80 weeks was −22.9 (4 mg), −34.3 (9 mg) and −31.7 (12 mg) events per hour, versus −9.9 with placebo. The differences from placebo were −13.0, −24.4 and −21.9 events per hour.
• TRIUMPH-2-OSA (with type 2 diabetes). Mean AHI change was −19.2 (4 mg), −24.7 (9 mg) and −25.4 (12 mg) events per hour, versus −10.3 with placebo. The differences from placebo were −8.9, −14.4 and −15.1 events per hour.
• Body weight (key secondary end point). Mean 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, versus −4.8% and −5.6% with placebo.
• Adverse events. The abstract states that the most common adverse events were gastrointestinal. It gives no rates.

The AHI fell less in participants with type 2 diabetes, at every dose, than in those without it. Weight loss in people with type 2 diabetes was also smaller in the companion TRIUMPH-2 paper in The Lancet. The TRIUMPH-1-OSA result was also summarized as one of the primary outcomes in the September TRIUMPH-1 obesity paper; the October paper is the trials’ own report, and it adds TRIUMPH-2-OSA.

Two estimands, similar answers

The headline figures use what the authors call a hybrid-treatment estimand: “a hypothetical strategy used for participants who had intercurrent events suggesting treatment failure and a treatment-policy strategy used elsewhere.” The paper also reports intention-to-treat results, which count every randomized participant as assigned. On that estimand the differences from placebo were −13.2, −24.7 and −22.5 events per hour in TRIUMPH-1-OSA and −8.8, −13.9 and −15.0 in TRIUMPH-2-OSA, close to the hybrid figures.

Tirzepatide is already approved for sleep apnea

Retatrutide is entering an indication where a related drug is already approved. On December 20, 2024, the FDA approved Zepbound (tirzepatide) for moderate to severe obstructive sleep apnea in adults with obesity. Sally Seymour, M.D., of the FDA’s Center for Drug Evaluation and Research, called it “the first drug treatment option for certain patients with obstructive sleep apnea.” The approval rested on two 52-week trials (SURMOUNT-OSA) of 469 adults without type 2 diabetes, at 10 or 15 mg once weekly. In those trials the AHI changed by −25.3 and −29.3 events per hour with tirzepatide versus −5.3 and −5.5 with placebo.

The two programmes cannot be ranked from these numbers. No trial has compared retatrutide with tirzepatide. The trials ran for different lengths of time (80 weeks against 52), started from different baseline AHI values, and TRIUMPH-2-OSA enrolled people with type 2 diabetes, whom SURMOUNT-OSA did not.

What this is, and isn’t

This is a report on a published trial paper, read from its abstract. Retatrutide is not approved by the FDA or any other regulator, for sleep apnea or anything else, and these results do not make it available. Products sold online as research-grade retatrutide are not the product tested in these trials. Nothing here is medical advice, a dosing recommendation or a usage recommendation.

Sources

• Grunstein RR, Somers VK, Azarbarzin A, Malhotra A, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. N Engl J Med, Oct. 21, 2026 (PubMed record and abstract) — primary: every TRIUMPH-1-OSA and TRIUMPH-2-OSA figure and quote. DOI 10.1056/NEJMoa2611477. Read November 5, 2026.
• ClinicalTrials.gov NCT05929066 (TRIUMPH-1) and NCT05929079 (TRIUMPH-2) — the registry records the paper names.
• FDA Approves First Medication for Obstructive Sleep Apnea. FDA press announcement, Dec. 20, 2024 — primary: the Zepbound approval, the quote and the trial description. Read November 5, 2026.
• Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). N Engl J Med, 2024;391:1193–1205 (PubMed record and abstract) — primary: the tirzepatide AHI figures. Read November 5, 2026.