In an adult with obesity (BMI ≥ 30 kg/m²) and moderate‑to‑severe obstructive sleep apnea, which medication—Zepbound (tirzepatide) or Wegovy (semaglutide)—has an FDA‑approved indication for treating the sleep apnea?

Zepbound (Tirzepatide) Has FDA Approval for Sleep Apnea

Zepbound (tirzepatide) is the only medication with FDA approval specifically for treating moderate-to-severe obstructive sleep apnea in adults with obesity, while Wegovy (semaglutide) does not have this indication. 1, 2, 3

FDA-Approved Indication

• Tirzepatide received FDA approval in 2024 for managing moderate-to-severe OSA (AHI ≥15 events/hour) in adults with obesity (BMI ≥30 kg/m²), making it the first medication ever approved by the FDA specifically for OSA treatment 3, 4
• This approval was based on the SURMOUNT-OSA trial, which demonstrated significant reductions in apnea-hypopnea index and improvements in oxygen desaturation, blood pressure, and cardiovascular risk factors 2, 5
• Semaglutide (Wegovy) is FDA-approved only for obesity management (approved 2021) and does not carry a specific indication for sleep apnea treatment 6

Clinical Evidence Supporting Tirzepatide for OSA

• In the SURMOUNT-OSA program, tirzepatide showed significant improvements in peripheral AHI as early as Week 4, with treatment differences versus placebo becoming significant by Week 20 for both AHI and sleep apnea-specific hypoxic burden 2
• The magnitude of AHI and hypoxic burden reductions correlated directly with achieved weight reduction, though additional research is needed to determine whether benefits are purely weight-mediated or involve direct respiratory effects 2, 3
• Tirzepatide produced mean weight loss of 20.9% at 72 weeks (15 mg dose), 19.5% (10 mg dose), and 15.0% (5 mg dose) versus 3.1% for placebo in obesity trials 6

Guideline-Based Context for Use

• The American Thoracic Society recommends anti-obesity pharmacotherapy for patients with OSA and BMI ≥27 kg/m² who have failed comprehensive lifestyle intervention (reduced-calorie diet, exercise, and behavioral counseling for typically 3-6 months) 1, 7
• Failure criteria include weight loss <5% at 3 months or insufficient improvement in OSA symptoms/AHI despite lifestyle modifications 1, 7
• While liraglutide (a GLP-1 agonist like semaglutide) showed AHI reductions of -6.1 events/hour in the SCALE trial of OSA patients, it does not have FDA approval for OSA and the evidence quality was limited by manufacturer funding and high dropout rates 6

Clinical Algorithm for Medication Selection

For adults with obesity (BMI ≥30 kg/m²) and moderate-to-severe OSA:

1. First-line: Comprehensive lifestyle intervention for 3-6 months (reduced-calorie diet of 1,000-1,200 kcal/day, exercise, behavioral counseling) 7, 8

2. If inadequate response (<5% weight loss or persistent OSA): Escalate to tirzepatide (Zepbound) as the only FDA-approved pharmacotherapy specifically indicated for OSA 1, 3

3. If BMI ≥35 kg/m² and pharmacotherapy fails: Refer for bariatric surgery evaluation 7

Important Caveats

• Tirzepatide represents a shift from purely symptom-based management (CPAP) toward a disease-modifying, weight-centered strategy that treats OSA as a chronic metabolic disease 3
• The medication must be used in conjunction with lifestyle modifications and may require lifelong use, as weight regain occurs after cessation 6
• Contraindications must be ruled out, including active cardiovascular disease and contraindications to GLP-1/GIP receptor agonist therapy 1
• While semaglutide has superior cardiovascular outcomes data (SELECT trial showing 20% reduction in MACE) and may indirectly benefit OSA through weight loss, it lacks the specific FDA indication for sleep apnea treatment 6