Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity

The SURMOUNT-OSA trials consisted of two phase 3, randomized, double-blind, placebo-controlled studies that evaluated tirzepatide in adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity. A total of 469 participants were enrolled: in Trial 1, patients not receiving positive airway pressure (PAP) therapy; in Trial 2, patients on active PAP therapy. Participants received tirzepatide (maximum dose 10 or 15 mg weekly) or placebo over 52 weeks.

The primary endpoint was the change in apnea-hypopnea index (AHI), the main marker of OSA severity:

• Trial 1: reduction of 25.3 events/hour with tirzepatide vs. 5.3 with placebo (difference of 20.0 events/hour; P<0.001)
• Trial 2: reduction of 29.3 events/hour with tirzepatide vs. 5.5 with placebo (difference of 23.8 events/hour; P<0.001)
• 42% of patients in Trial 1 and 50% in Trial 2 achieved disease resolution (AHI <5 or AHI 5-14 without daytime sleepiness)

Secondary endpoints demonstrated broad benefits: weight loss of 18-20%, significant improvement in nocturnal respiratory symptoms, decrease in systolic blood pressure (~8 mmHg), reductions in hsCRP and metabolic markers. The adverse event profile was consistent with other tirzepatide studies, with transient gastrointestinal effects being most common.

This was the first phase 3 trial to demonstrate that an obesity pharmacotherapy can directly treat a respiratory comorbidity of obesity. In December 2024, the FDA approved tirzepatide for obesity-associated OSA in adults, making it the first medication approved specifically for this indication and significantly expanding the clinical relevance of dual GIP/GLP-1 agonists.