Retatrutide Cuts Sleep Apnea Events in Phase III Trials

RETATRUTIDE significantly reduced nighttime breathing disruptions in adults with obstructive sleep apnea across two randomized clinical trials.

The investigational once-weekly injection demonstrated substantial improvements in sleep apnea severity among adults with overweight or obesity, regardless of whether they had type 2 diabetes.

Retatrutide for Obstructive Sleep Apnea

Two Phase III, double-blind, placebo-controlled trials evaluated retatrutide in adults with moderate-to-severe obstructive sleep apnea (OSA) and a body mass index of at least 27.

TRIUMPH-1-OSA enrolled 243 participants without type 2 diabetes, while TRIUMPH-2-OSA included 448 participants with the condition.

Participants received weekly subcutaneous injections of retatrutide at doses of 4 mg, 9 mg, or 12 mg, or placebo, over 80 weeks.

Retatrutide targets three hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Researchers assessed changes in the apnea-hypopnea index (AHI), which measures breathing interruptions per hour of sleep.

Sleep Apnea Events Fall Significantly

In TRIUMPH-1-OSA, participants receiving retatrutide 9 mg experienced an average reduction of 34.3 breathing events per hour, compared with 9.9 events with placebo.

The 12 mg dose reduced events by 31.7 per hour, representing a placebo-adjusted difference of 21.9 events per hour. The corresponding difference for the 9 mg dose was 24.4 events per hour.

Among participants with type 2 diabetes in TRIUMPH-2-OSA, retatrutide 9 mg and 12 mg reduced breathing events by 24.7 and 25.4 per hour, respectively, compared with 10.3 events with placebo.

Both higher doses produced significantly greater improvements than placebo across the trials.

Weight Loss Accompanies Respiratory Improvements

Substantial weight reductions accompanied improvements in sleep apnea severity.

Participants receiving retatrutide lost an average of 12.5–22.2% of their body weight in TRIUMPH-1-OSA, compared with 4.8% among placebo recipients.

In TRIUMPH-2-OSA, weight reductions ranged from 12.1–18.5%, compared with 5.6% with placebo.

Gastrointestinal symptoms were the most frequently reported adverse events.

Implications for Sleep Apnea Treatment

The findings suggest that retatrutide could become a promising treatment option for adults with obstructive sleep apnea and excess body weight, including those with type 2 diabetes.

Although the results demonstrate significant improvements in breathing disturbances and body weight, the drug remains investigational. Further evaluation will help establish its role in clinical practice.

Reference
Grunstein RR et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. N Engl J Med. 2026. doi:10.1056/NEJMoa2611477.

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