P018 Pharmacotherapy for OSA: a critical review of randomised placebo-controlled trials

Abstract Introduction Positive airway pressure (PAP) therapy remains the gold standard treatment for obstructive sleep apnoea (OSA), but challenges with adherence, acceptability, and side effects persist. Interest in pharmacological therapies has grown over the past two decades, culminating in the recent U.S. FDA approval of tirzepatide as the first pharmacotherapy for OSA. Our review critically examines the efficacy of pharmacologic treatments for OSA and highlights current limitations and future research directions in this evolving field. Methods We conducted a search of Medline and Embase for randomised controlled trials (RCTs) published from January 2005 to February 2025, identifying 41 RCTs investigating 37 different drugs or drug combinations. Results Weight-loss therapies showed the most consistent and substantial improvements in OSA severity. Tirzepatide produced the largest reduction in apnoea-hypopnoea index (AHI) and improved patient-reported outcomes and cardiometabolic risk factors. Other pharmacotherapies demonstrated modest and inconsistent effects on sleep apnoea severity sometimes with side-effects that contradict the treatment goal to reduce daytime sleepiness. Many promising approaches were often too early in their testing/re-purposing phase to demonstrate improvements in sleepiness or quality of life or any sustained improvement in sleep apnoea severity or were insufficiently targeted at the endotype they might best treat. Conclusion Pharmacotherapy for OSA is a rapidly evolving field. Weight-loss agents, particularly tirzepatide, represent a promising and now clinically viable treatment option. However, while endotype-targeted approaches are conceptually attractive, most drugs have not yet been tested in endotype-selected populations and remain investigational.