Anti-Obesity Pharmacotherapy and Emerging Multimodal Interventions for Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a major public health crisis affecting nearly one billion people worldwide and is associated with significant cardiovascular and metabolic complications. The prevalence of OSA is rising steadily due to the obesity pandemic and is contributed by interacting anatomical, inflammatory, and neuro-respiratory mechanisms. Continuous positive airway pressure (CPAP) remains the gold standard for the management of OSA; however, it does not address underlying obesity or weight-independent pathophysiology. Obesity is an important modifiable risk factor for OSA, as weight loss is associated with resolution/improvement of the disease. Therefore, growing evidence now supports surgical and medical management of obesity as complementary strategies to improve both body weight and apnea-hypopnoea index (AHI), prompting a paradigm shift towards integrated, multimodal care. Bariatric interventions typically achieve 25%-35% total weight loss and yield significant but variable reductions in AHI with remission rates of 50%-75%, driven by mechanical unloading, improved ventilatory control, and favorable metabolic and anti-inflammatory effects. However, it is constrained by eligibility, cost, and perioperative risks. Alternatively, Incretin-based therapies, particularly Tirzepatide, achieve 10%-22% weight loss and reduce AHI to 12-30 events per hour, securing the first regulatory approval for OSA based on the largest trial-level AHI reductions. The recent introduction of several therapeutic agents with excellent weight loss potential has reshaped the management landscape of people with obesity and OSA. This review aims to analyze the literature across surgical, endoscopic, and pharmacological interventions and OSA while proposing an individualized treatment framework integrating weight-loss pharmacotherapy with device-based and structured lifestyle strategies and surgical interventions, tailored to disease phenotypes.