Glucagon-Like Peptide-1 Receptor Agonists for Obstructive Sleep Apnea: A Review

Obstructive sleep apnea (OSA) affects nearly 1 billion adults worldwide and is independently associated with cardiovascular disease, stroke, and increased mortality. While continuous positive airway pressure (CPAP) remains the criterion standard treatment, adherence rates of only 30% to 60% limit its population-level effectiveness. Obesity is present in 60% to 70% of patients with OSA and represents the primary modifiable risk factor, yet, until recently, no pharmacological therapies specifically targeted this pathophysiological mechanism. The December 2024 US Food and Drug Administration approval of tirzepatide as the first medication indicated for moderate to severe OSA in adults with obesity represents a paradigm shift toward disease-modifying pharmacotherapy, with implications for otolaryngologic practice.

Six meta-analyses demonstrated consistent apnea-hypopnea index (AHI) reductions with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), ranging from -5.7 to -21.9 events per hour. The SURMOUNT-OSA phase 3 trials showed that tirzepatide reduced AHI by 20 to 24 events per hour vs placebo, with 42% to 50% of patients experiencing disease remission (AHI, <5 events per hour or <15 without symptoms). Weight loss is the primary established mechanism, with GLP-1 RAs reducing tongue fat and parapharyngeal adipose tissue that contribute to upper airway collapse. Emerging preclinical evidence has suggested potential weight-independent effects through carotid body glucagon-like peptide 1 receptor modulation of chemosensitivity (affecting loop gain), leptin pathway interactions that are associated with upper airway neuromuscular control, and NLRP3 inflammasome suppression. However, GLP-1 RAs did not match CPAP efficacy (approximately22 vs 31 events per hour of an AHI reduction), cardiovascular outcome benefits remain unproven, and weight regain commonly occurs after discontinuation.

This review suggest that GLP-1 RAs offer otolaryngologists a disease-modifying adjunct for obesity-related OSA that is best positioned as complementary therapy alongside CPAP, preoperative optimization before upper airway surgery, or potentially to expand hypoglossal nerve stimulator candidacy. They are appropriate for patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) greater than 30 who are CPAP-intolerant or have obesity-related comorbidities but are unlikely to benefit individuals without obesity or those with primarily anatomical obstruction. Critical evidence gaps include associations with pharyngeal critical closing pressure, drug-induced sleep endoscopy collapse patterns, and hypoglossal nerve stimulator combination therapy outcomes.