Tirzepatide Could Offer a Novel Approach to Sleep Apnea Treatment

Obstructive sleep apnea affects more than 900 million individuals worldwide. The common respiratory disorder arises from insistent pharyngeal collapse during sleep, resulting in a temporary pause of breathing or shallow breathing. Although treatment has long been associated with mechanical support during sleep, results have been underwhelming. Randomized controlled trials have failed to confirm that positive airway pressure therapy reduces the number of adverse cardiovascular outcomes and death.

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It is well understood that being overweight or obese is a significant risk factor for obstructive sleep apnea. Current clinical guidelines recommend evidence-based weight loss programs as a component of obstructive sleep apnea management, but have yet to consider pharmacologic options as a potential solution. The New England Journal of Medicine recently published the results of the SURMOUNT-OSA trials that evaluated tirzepatide (Mounjaro, Zepbound; Lilly) in adults with moderate-to-severe obstructive sleep apnea and obesity.

Tirzepatide is a long-acting dual glucose-dependent insulinotropic receptor and glucagon-like peptide-1 receptor agonist. Treatment with tirzepatide has led not only to significant reductions in excess body weight, but also improvements in blood pressure and reduction of inflammatory markers. The SURMOUNT-OSA consisted of 2 52-week, double-blind, randomized control trials. One included participants receiving stable continuous positive airway pressure (CPAP) therapy, while the other involved participants who had failed CPAP.

The apnea-hypopnea index (AHI, defined as the number of apneas and hypopneas during an hour of sleep) decreased significantly to approximately 29.3 events per hour (a 58.7% change from baseline) among patients receiving tirzepatide. The American Academy of Sleep Medicine currently defines an AHI of 15 or greater per hour as the threshold of moderate sleep apnea. A proposed 50% reduction in AHI events would hold significant clinical relevance.

Additionally, reductions in AHI also resulted in noteworthy improvements in hypoxic burden, a key contributor to cardiovascular complications associated with obstructive sleep apnea. This was true across both trials, regardless of concomitant CPAP therapy. This offers a potential alternative solution to patients unable or unwilling to maintain adherence with current CPAP therapies.

Excessive daytime sleepiness, a downstream symptom of recurrent arousals often associated with obstructive sleep apnea, improved in both trials. Participants who received tirzepatide reported improvements in both sleep-related functioning and frequency of sleep disturbances.

Pharmacologic weight loss interventions may revolutionize the clinicians think about obstructive sleep apnea management. This novel approach may be able to replace, or at the very least bolster, current treatment options.

REFERENCE

Malhotra A, Bednarik J, Chakladar S, et al. Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemp Clin Trials. 2024;141:107516. doi:10.1016/j.cct.2024.107516