Current Updates on Pharmacotherapy for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with substantial cardiovascular morbidity and mortality. Although positive airway pressure (PAP) remains the gold-standard treatment, poor long-term adherence often limits its clinical effectiveness, underscoring the need for safe and effective pharmacological alternatives. Advances in the understanding of OSA endotypes, including anatomical collapsibility, upper airway muscle responsiveness, arousal threshold, and loop gain, have shifted research toward precision pharmacotherapy. Early studies of single-agent therapies, such as protriptyline and acetazolamide, were limited by modest efficacy or clinically significant adverse effects. More recent dual-drug combinations and anti-obesity medications have shown greater promise. In particular, atomoxetine plus oxybutynin has demonstrated significant reductions in the apnea-hypopnea index (AHI) by enhancing upper airway muscle tone across sleep stages. In parallel, glucagon-like peptide-1 receptor agonists have substantially changed the management of obesity-related OSA. Tirzepatide, in particular, has produced marked weight loss of nearly 20% and an AHI reduction of more than 50%, leading to its recent U.S. Food and Drug Administration approval for OSA. Despite earlier skepticism, the shift from broad-spectrum agents toward endotype-specific and metabolic-targeted therapies may improve the management of selected patients with OSA. However, long-term safety and cost-effectiveness require further evaluation before these emerging pharmacological options can be broadly integrated into care for patients who cannot tolerate conventional PAP therapy.