TOPLINE:

In adults with obesity, type 2 diabetes (T2D), and obstructive sleep apnea, the initiation of incretin receptor agonists, particularly tirzepatide, was associated with lower risks for continuous positive airway pressure (CPAP) use, hospitalization, and all-cause mortality compared with the initiation of SGLT2 inhibitors.

METHODOLOGY:

• Incretin receptor agonists, such as tirzepatide, have shown promising effects in reducing the severity of obstructive sleep apnea in recent randomized clinical trials, but real-world evidence on their effectiveness remains limited.
• Researchers conducted a target trial emulation to assess whether the initiation of incretin receptor agonists in adults with obesity, T2D, and obstructive sleep apnea was associated with a lower risk for CPAP use.
• They analyzed data of 36,981 patients who initiated incretin receptor agonists (mean age, 62.3 years; 39.7% women) and propensity score-matched them to an equal number of patients who initiated SGLT2 inhibitors.
• The outcomes included CPAP use, all-cause mortality, and hospitalization.
• The mean follow-up duration was 332.2 days, with the follow-up period beginning 30 days after treatment initiation.

TAKEAWAY:

• Compared with SGLT2 inhibitor use, incretin receptor agonist use was associated with an 8% lower risk for CPAP use (hazard ratio [HR], 0.92; 95% CI, 0.87-0.97); in sex-stratified analyses, no significant association was observed among women.
• The initiation of incretin receptor agonists was associated with a 32% reduced risk for all-cause mortality (HR, 0.68; 95% CI, 0.60-0.77) and 10% reduced risk for hospitalization (HR, 0.90; 95% CI, 0.86-0.95).
• Both tirzepatide and GLP-1 receptor agonists were associated with reduced risks for CPAP use and all-cause mortality compared with SGLT2 inhibitors, with tirzepatide showing more pronounced effects.

IN PRACTICE:

“Notably, tirzepatide showed greater reductions in risk of CPAP use and mortality than GLP-1 RAs [receptor agonists], highlighting its potential therapeutic advantage,” the authors wrote.

SOURCE:

The study was led by Huilin Tang, PhD, Center for Health AI and Synthesis of Evidence, University of Pennsylvania, Philadelphia. It was published online on December 22, 2025, in JAMA Network Open.

LIMITATIONS:

Procedural records for CPAP may not have reflected actual use, adherence, or the severity of obstructive sleep apnea. Unmeasured confounders, including socioeconomic status and the severity of obstructive sleep apnea, could have influenced these associations.

DISCLOSURES:

This study was supported by the National Institutes of Health (NIH). One author reported receiving grants from the NIH and other organizations; another reported receiving personal fees from several healthcare companies for work unrelated to this study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.