Oral GLP-1 shows promise for sleep apnea

Clinical takeaway: Consider once-daily orforglipron a potential future treatment option for adults with moderate to severe obstructive sleep apnea and excess weight. These findings do not establish that it can replace positive airway pressure.

Positive airway pressure (PAP) remains first-line for obstructive sleep apnea (OSA), but tolerability and patient preferences limit its use. Once-weekly injectable tirzepatide is already approved for adults with obesity and moderate to severe OSA. Once-daily oral orforglipron could expand treatment options.

At 52 weeks, the apnea-hypopnea index (AHI) fell about 35% with orforglipron versus 5% with placebo among participants not using PAP, and 26% versus 3% among PAP users. These changes represented about 12-13 fewer breathing events per hour beyond placebo.

Weight decreased about 10%-11% with orforglipron versus 1%-2% with placebo, and sleep apnea-related hypoxic burden improved. However, patient-reported sleep-related impairment (alertness, sleepiness, tiredness, and daytime functioning) did not improve significantly versus placebo in the main analysis.

Gastrointestinal adverse events occurred in about 68%-71% of orforglipron recipients versus 37% with placebo, generally with mild to moderate severity. Adverse events prompted treatment discontinuation in 7%-12% versus 1%-4%.

The Lilly-funded ATTAIN-OSA program comprised two randomized, double-blind, placebo-controlled phase 3 trials involving 712 adults with a body mass index (BMI) of 27 or higher and moderate to severe OSA. Diabetes was excluded. The primary outcome was AHI change at 52 weeks, with PAP users stopping therapy for seven days before assessments.

Longer-term studies are needed to establish durability and clarify benefits in excluded populations, including patients with diabetes, mild OSA, or a BMI under 27.

“Patient-reported outcomes are an important complement to objective measures of sleep-disordered breathing,” the authors wrote.

Source: Malhotra A, et al. (2026 Nov 9) JAMA. Orforglipron for Obstructive Sleep Apnea: Results From 2 Randomized Clinical Trials (ATTAIN-OSA)