Tirzepatide for the treatment of obstructive sleep apnea: from apnea-hypopnea index reduction to cardiometabolic risk mitigation–a narrative review

BACKGROUND: Obstructive sleep apnea (OSA) is a chronic respiratory disorder with nocturnal oxygen desaturation that is often associated with multisystemic sequelae such as hypertension, cardiovascular diseases, and increased morbidity and mortality. Obesity has been proposed as a modifiable risk factor; hence, the recent shift in focus to investigating anti-obesity medications for the management of OSA. Tirzepatide is the first U.S. FDA-approved pharmacotherapy for the treatment of moderate-to-severe OSA in adults with obesity to be utilized in combination with low caloric intake and physical activity, given its prior success in managing type 2 diabetes (T2D) and obesity. METHODS: This narrative review evaluates tirzepatide and the SURMOUNT-OSA trial program as the key contemporary anchors for the pharmacological treatment of OSA in adults with concurrent obesity. Because the randomized evidence base currently comprises a single pivotal trial program, the review centers on SURMOUNT-OSA and its prespecified endpoints along with post hoc analyses, supplemented by observational, modeling, and mechanistic studies. RESULTS: In the SURMOUNT-OSA program, tirzepatide produced randomized, placebo-controlled reductions in the apnea-hypopnea index, sleep apnea-specific hypoxic burden, body weight, and systemic inflammation. The program was designed around respiratory and metabolic endpoints rather than clinical events, so it cannot support conclusions about mortality, cardiovascular, or renal outcomes. Favorable signals for those events, including all-cause mortality, major adverse kidney events, and major adverse cardiovascular events, come only from nonrandomized observational cohorts and are best regarded as directional and exploratory rather than definitive. CONCLUSIONS: Tirzepatide may help frame OSA as a multifactorial and partially metabolically treatable disease and may represent a clinically meaningful expansion of treatment options alongside, rather than as a replacement for, established mechanical and procedural therapies. The available evidence is anchored in a single phase 3 trial program and limited by short follow-up and the absence of definitive comparative and long-term outcome data. Long-term durability of effect after discontinuation, generalizability beyond the SURMOUNT-OSA-eligible population, OSA-specific economic analysis, and head-to-head comparisons against CPAP remain the principal unsettled questions requiring dedicated long-term studies before firm clinical recommendations can be made.