Rethinking OSA Management With GLP-1 Receptor Agonists: Part 2
In Part 2 of this interview, Ali El Sohl, MD, professor, University of Buffalo, offers further thoughts on the findings of his narrative review exploring GLP-1 receptor agonists (GLP-1 RAs) for management of obstructive sleep apnea (OSA), published in Expert Opinion on Pharmacology. Dr El Sohl explains how exactly GLP-1 RAs improve OSA symptoms beyond weight loss and also offers thoughts on how they might be integrated into current OSA treatment protocols. Finally, he reflects on lingering questions on this topic as well as areas of inquiry for future research.
Missed Part 1 of this interview? Find it here.
For more expert insights, visit the Sleep Disorders Excellence Forum.
Pulmonology Learning Network (PLN): Could you elaborate on how GLP-1 RAs may mechanistically improve OSA symptoms? Are these effects purely weight-related, or do they extend to inflammatory or neuromuscular pathways as well?
Ali El Sohl, MD: GLP-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have demonstrated efficacy in reducing the severity of obstructive sleep apnea (OSA) through mechanisms that extend beyond weight loss. While GLP-1 RAs promote substantial weight loss, leading to reductions in fat deposits around the upper airway, thereby improving airway patency and reducing the frequency of apneic events, GLP-1 RAs have been shown to lower markers of inflammation, such as high-sensitivity C-reactive protein, which could translate into reduction of cardiovascular events. GLP-1 RAs could stabilize breathing patterns during sleep by modulating neurotransmitter pathways involved in respiratory control.
PLN: How might GLP-1 RAs be integrated into current OSA treatment protocols? Would you see them as adjuncts to CPAP or as alternatives in certain patient subgroups?
Dr El Sohl: GLP-1 RAs can serve as adjunctive therapy to CPAP by promoting weight loss, which may reduce the required CPAP pressure settings and enhance overall treatment efficacy. For patients who are intolerant to CPAP therapy, GLP-1 RAs offer a non-invasive alternative. The FDA's approval of tirzepatide for treating moderate to severe OSA in adults with obesity underscores its potential as a standalone therapy in this subgroup. Nonetheless, the use of GLP-1 RAs should not be considered as a substitute or replacement for CPAP therapy. Despite the impressive results of weight loss attributed to GLP-1RAs, complete resolution of sleep apnea occurs in less than half of the patients. More importantly the weight reduction benefits are sustained as long as these drugs are being used. Once discontinued, patients may regain a substantial portion of the weight lost during treatment. For instance, in the STEP 1 trial, participants regained approximately two-thirds of their prior weight loss within one year after stopping semaglutide. This weight gain was associated with a deterioration in OSA severity.
PLN: What are the most pressing questions that still need to be answered in this space, and what future research directions do you consider most promising?
Dr El Sohl: While GLP-1 RAs have demonstrated significant weight loss and improvements in OSA severity, the sustainability of these benefits post-discontinuation is uncertain. Studies indicate that cessation often leads to weight gain, potentially reversing OSA improvements. Moreover, long-term safety data specific to OSA patients are limited. Common side effects include gastrointestinal disturbances (nausea, vomiting), but rare adverse events such as pancreatitis and gallbladder disease have been reported. Moreover, the high cost of GLP-1 RAs, ranging from $11,500 to $14,000 annually, poses significant barriers to widespread use. Insurance coverage is inconsistent, and many patients face out-of-pocket expenses that limit access. Future research should focus on 1) mechanistic studies exploring non-weight-related effects of GLP-1 RAs on sleep-disordered breathing, 2) development of guidelines for integrating GLP-1 RAs into existing OSA treatment protocols, and 3) identifying factors that predict individual response to GLP-1RAs and tailoring treatment accordingly.
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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