Targeting obesity could benefit a large proportion of patients with obstructive sleep apnea (OSA). GLP-1 receptor agonist (RA)-based treatments offer a promising therapeutic approach, but the phenotypes that respond best — either alone or in combination with continuous positive airway pressure (CPAP) — still need to be identified to enable personalized care. The update was presented in 2026 at the European Respiratory Society Congress in Barcelona, Spain.

OSA syndrome is a major public health problem: Among people aged 30-69 years, 936 million have an apnea-hypopnea index (AHI) ≥ 5 events per hour, including 425 million with moderate-to-severe OSA (AHI ≥ 15 events per hour).

OSA is an independent risk factor for cardiovascular and metabolic disease. “CPAP is highly effective at improving symptoms,” said Silke Ryan, consultant in respiratory and sleep medicine at St. Vincent’s University Hospital and clinical professor at University College Dublin, both in Dublin, Ireland. “However, CPAP alone is not consistently effective at preventing or treating cardiometabolic complications.”

Furthermore, the incidence and severity of OSA increase progressively with rising BMI. In a prospective study, a 10% weight gain increased the risk of developing moderate-to-severe sleep-disordered breathing by a factor of 6 (95% CI, 2.2-17).

Narrowing of the upper airways increases the degree of pharyngeal obstruction and airway collapsibility. A decrease in functional residual capacity reduces the longitudinal traction exerted on the pharynx, further promoting its collapsibility. Finally, increased leptin levels and leptin resistance heighten the sensitivity of the ventilatory feedback loop, contributing to increased ventilatory instability.

Remarkable Results

Because obesity is a major pathogenic factor in OSA, weight loss could play an increasingly important role in its management, especially because obesity treatments enable significant weight reduction and provide cardiovascular and metabolic benefits beyond OSA.

There is one caveat, however: Even after bariatric surgery, OSA remission is achieved in only about 65% of patients.

“Before the advent of the new generations of GLP-1 receptor agonist treatments,” the expert explained, “a 10% weight loss was associated with a reduction of approximately 35% in the AHI. However, we now have highly effective pharmacologic treatments targeting GLP-1, notably tirzepatide,” the speaker noted.

The SURMOUNT-OSA study assessed tirzepatide’s efficacy in obesity-related OSA in a randomized, double-blind, placebo-controlled trial involving 469 patients followed for 52 weeks. The study included patients with moderate-to-severe OSA who were either CPAP-naive in trial 1 or already using CPAP in trial 2. The treatment resulted in a reduction of approximately 20% in body weight after 1 year, accompanied by a significant improvement in OSA: The AHI decreased by an average of 25.3 events per hour in trial 1 and 29.3 events per hour in trial 2 after 52 weeks.

“These results were so remarkable that the FDA has since approved tirzepatide as a pharmacologic option for the treatment of OSA,” commented the expert.

A Game Changer for Sleep Apnea?

Not really, said Ryan, who offered some caveats: “First of all, not all patients with OSA are obese,” she pointed out. According to unpublished data from the European Sleep Apnea Database (ESADA) cohort, approximately 60% of patients with OSA are obese. That means about 40% are not. Thus, only 34% of patients with OSA would meet the SURMOUNT-OSA criteria. Although obesity contributes to the pathophysiology of OSA through multiple mechanisms, OSA is not necessarily dependent on the presence of obesity.

Furthermore, the effect of weight loss on the severity of OSA is not linear. In the SURMOUNT-OSA study, about half of the patients still had residual disease, defined as either an AHI ≥ 15 events per hour or an AHI of 5-14 events per hour combined with an Epworth Sleepiness Scale (ESS) score ≥ 10, a self-administered questionnaire used to assess excessive daytime sleepiness. “Despite the improvement achieved, a substantial proportion of patients therefore still have clinically significant OSA,” she noted.

Data on patient-centered outcomes, or patient-reported outcome measures, remain limited for these treatments. In SURMOUNT-OSA, tirzepatide was associated with improvements in sleep quality, daytime functioning, and quality of life. However, in patients using CPAP, tirzepatide did not result in an improvement in the ESS score.

Ultimately, the data remain insufficient, particularly in the absence of a direct comparison between GLP-1 RAs and CPAP regarding patient-centered outcomes and long-term benefits.

What Is the Cardiovascular Impact?

A key question concerns the impact of these GLP-1 RA-based treatments on cardiovascular risk. With CPAP, the reduction in vascular inflammation is associated with improved endothelial function, proportional to the increase in nocturnal oxygenation.

A randomized “proof-of-concept” study suggests that CPAP — but not weight loss mediated by a GLP-1 RA — reduces vascular inflammation and the volume of unstable atherosclerotic plaques in patients with OSA.

“The results from SURMOUNT-OSA are encouraging, but long-term data are still needed,” said Ryan. Indeed, weight loss with tirzepatide requires sustained adherence. In SURMOUNT-4, nearly half of the weight lost was regained within 1 year after discontinuing tirzepatide and switching to placebo.

That is why, according to the pulmonologist, “these treatments remain insufficiently studied in certain populations, particularly in OSA, to consider broader use.” We still need to be prepared for this, she pointed out. In ESADA, nearly 42% of participating centers initiated treatment with GLP-1 RAs.

She concluded: “In my view, combination therapy could offer the best approach for the majority of patients with OSA and obesity by simultaneously and optimally targeting the mechanisms and burden specific to each condition.”

Ryan reported receiving grants or research support from Novo Nordisk and Fitbit. She also reported receiving honoraria or consultation fees from the Irish Rugby Football Union, the American College of Cardiology, and the Chinese Thoracic Society. 

This story was translated from Medscape's French edition.