Tirzepatide for Obstructive Sleep Apnea: Trial Evidence, Cardiometabolic Effects, and Implications for Cardiovascular...

Obstructive sleep apnea affects approximately one billion adults worldwide and is associated with hypertension, atrial fibrillation, heart failure, and stroke. Obesity is its dominant reversible cause, yet positive airway pressure therapy splints the pharyngeal airway without addressing the adiposity that narrows it, and randomized trials have not shown that it reduces cardiovascular events. In December 2024, the United States Food and Drug Administration approved tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as the first drug for moderate-to-severe obstructive sleep apnea in adults with obesity. We summarize the pharmacology of tirzepatide and the anatomic basis by which weight reduction improves upper airway patency, notably reduction of tongue and parapharyngeal fat. We then review the SURMOUNT-OSA program: two parallel 52-week, double-blind, placebo-controlled phase 3 trials enrolling 469 adults with obesity and an apnea-hypopnea index of at least 15 events per hour, one conducted without positive airway pressure and one during established positive airway pressure use. Tirzepatide reduced the apnea-hypopnea index by an estimated 20.0 and 23.8 events per hour relative to placebo, with concurrent reductions in sleep apnea-specific hypoxic burden, body weight, systolic blood pressure, and high-sensitivity C-reactive protein.