Rethinking OSA Management With GLP-1 Receptor Agonists

Can pharmacologic weight loss therapy redefine how we manage obstructive sleep apnea (OSA) beyond CPAP? In this interview, Ali El Sohl, MD, MPH, professor, University of Buffalo, discusses data from his narrative review published in Expert Opinion on Pharmacology on GLP-1 receptor agonists—like liraglutide, semaglutide, and tirzepatide—and their potential to directly impact OSA severity by targeting fat deposition in the upper airway. Discover practical insights that may help guide treatment decisions in OSA patients with comorbid obesity or type 2 diabetes.

For more expert insights, visit the Sleep Disorders Excellence Forum here on Pulmonology Learning Network. 

Pulmonology Learning Network (PLN): What clinical gap or unmet need prompted your team to explore the role of GLP-1 receptor agonists in the management of OSA?

Ali El Sohl, MD, MPH: The impetus to investigate the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing obstructive sleep apnea (OSA) arises from a confluence of clinical challenges and emerging therapeutic opportunities. Traditional treatments for OSA do not address the underlying pathophysiological basis of sleep apnea. While continuous positive airway pressure (CPAP) therapy is considered the gold standard therapy for OSA by overcoming upper airway obstruction, it primarily addresses the mechanical aspect of upper airway obstruction without targeting underlying anatomical and physiological contributors. Besides, CPAP often suffers from poor adherence due to discomfort, inconvenience, and potential weight gain. Given these insights, there's growing interest in therapies that tackle the underlying fat accumulation contributing to OSA. This has led to the exploration of pharmacological agents, such as GLP-1 receptor agonists, which promote weight loss and may reduce fat deposits around the upper airway, offering a complementary approach to traditional CPAP therapy. 

PLN: GLP-1 RAs are well-established in the management of type 2 diabetes and obesity. What was the rationale for specifically evaluating their impact on OSA symptoms?

Dr El Sohl: GLP-1 RAs, such as liraglutide, semaglutide, and tirzepatide, have demonstrated significant weight loss effects in patients with type 2 diabetes and obesity. With the established paradigm that excess adipose tissue, particularly in the neck and upper airway, contributes to OSA pathophysiology, it was posited that GLP-1 RAs could reduce OSA severity by decreasing fat deposition in these areas. Studies have shown that improvements in sleep propensity and OSA severity due to GLP-1RA interventions in patients with type 2 diabetes were significantly correlated with reductions in weight loss, BMI and waist circumference. 

PLN: In synthesizing the data for this review, what were some of the methodological challenges or limitations you encountered when comparing outcomes across trials involving liraglutide, semaglutide, and tirzepatide?

Dr El Sohl: Analyzing data across trials of liraglutide, semaglutide, and tirzepatide presented methodological challenges, primarily due to differences in study design, populations, and outcomes measured. Specifically, the inclusion criteria regarding baseline body mass index (BMI), severity of OSA, and presence of comorbidities like type 2 diabetes mellitus (T2DM) vary across studies. The varying dosing schedules, study durations, and the inclusion of individuals with or without diabetes complicated direct comparisons. The limited duration may not capture the long-term efficacy and safety of these medications in OSA management. In addition, some studies do not adequately control for confounding variables such as concurrent use of continuous positive airway pressure (CPAP) therapy, lifestyle interventions, or other medications that may affect weight or sleep apnea severity. 

Stay tuned for Part 2 coming soon!

Ali A. El Sohl, MD, MPH, is a professor of medicine and epidemiology and environmental health at the University of Buffalo. He also holds a clinical and an administrative position at the VA WNY Healthcare System. He oversees the research operation at the VA Western New York and he also attends and supervises the sleep clinic at the VA. Dr El Sohl’s research focuses on the association between sleep apnea and cardiovascular diseases.

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