Obesity-related obstructive sleep apnea (OSA) is common, clinically heterogeneous, and tightly linked to cardiometabolic dysfunction, impaired daytime function, and reduced quality of life. Positive airway pressure (PAP) remains the standard device-based treatment for moderate-to-severe disease because it immediately stabilizes the upper airway, but it does not directly reverse the obesity that drives disease in many patients and its long-term effectiveness is often constrained by adherence. This narrative, non-systematic review synthesizes direct OSA-specific randomized evidence, indirect obesity-trial evidence, and mechanistic literature to clarify what is established, what is inferred, and what remains hypothetical. The clinical evidence for incretin therapy in OSA is promising but uneven. Direct OSA-specific randomized evidence is concentrated in liraglutide and tirzepatide: SCALE Sleep Apnea established proof of concept that pharmacologic weight loss can improve the primary apnea-hypopnea index (AHI) outcome, whereas in SURMOUNT-OSA change in AHI was the primary endpoint. Reductions in body weight, sleep apnea-specific hypoxic burden, selected patient-reported sleep outcomes, hsCRP, and systolic blood pressure were reported as key secondary or additional secondary findings, supporting a broader disease-burden signal but not proving long-term cardiovascular event reduction. Discordant vascular-imaging evidence further cautions that GLP-1-mediated weight loss should not be assumed to reproduce all vascular effects of PAP or to prove cardiovascular event reduction. Semaglutide provides important indirect obesity and cardiometabolic evidence, but direct OSA-specific outcome data remain limited; evidence from other incretin agents also remains largely indirect because most trials were designed for obesity or cardiometabolic endpoints rather than sleep outcomes. The most parsimonious mechanistic interpretation is weight-loss-mediated anatomical unloading. This interpretation is supported by non-incretin weight-loss imaging studies and upper-airway physiology, but it has not yet been directly confirmed by serial upper-airway imaging, Pcrit measurement, or physiological endotyping within incretin-treated OSA cohorts. This narrative review organizes the field into three evidence tiers: direct OSA-specific randomized trials, indirect obesity-trial evidence relevant to OSA, and mechanistic extrapolation. We argue that the current evidence is strong enough to position incretin therapy as a disease-modifying adjunct for selected patients with obesity-driven, anatomically dominant OSA, but not yet strong enough to support class-wide claims, routine PAP replacement, or confident attribution of benefit to direct modulation of non-anatomical endotypes.
