The 2024 American Diabetes Association (ADA) meeting brought forth remarkable findings with the potential to reshape the treatment landscape for obstructive sleep apnea (OSA) and obesity. The SURMOUNT-OSA trials, led by Dr. Atul Malhotra, vice chair of medicine for research and professor of medicine at University of California, San Diego, evaluated the efficacy of tirzepatide, a dual GIP and GLP-1 receptor agonist, in treating adults with moderate-to-severe OSA and obesity.

Obstructive sleep apnea is a prevalent condition characterized by repetitive pharyngeal collapse during sleep, leading to intermittent hypoxemia and disrupted sleep patterns. It is closely associated with obesity, a major reversible risk factor. OSA affects over 900 million people globally, with around 40% of cases being moderate-to-severe. The condition poses substantial health risks, including cardiovascular disease, metabolic syndrome, and diminished quality of life. There are currently no medications approved therapies for OSA. Traditional treatments, such as positive airway pressure (PAP) therapy, have shown variable effectiveness, often hindered by patient adherence issues.

Importance of the Study

The SURMOUNT-OSA trials are pivotal for several reasons. First, they address a critical gap in the treatment of OSA by introducing a pharmacologic option that targets the root cause—excess adiposity. Second, the trials comprehensively evaluate the multifaceted benefits of tirzepatide, beyond its weight reduction properties. This includes its impact on the apnea-hypopnea index (AHI), cardiovascular health markers, and patient-reported outcomes, offering a holistic treatment approach.

Study Design and Methods

The SURMOUNT-OSA trials comprised two phase 3, double-blind, randomized, controlled studies conducted at 60 sites across nine countries. They included adults with moderate-to-severe OSA and obesity, divided into two groups: one not receiving PAP therapy (trial 1; mean age, 47.9 years; 67.1% men, 65.8% white)and the other using PAP therapy (trial 2; mean age, 51.7 years; 72.3% men; 73.1% white). After a 4-week screening period, participants were randomized 1:1 to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. AHI was assessed at screening, week 20 and week 52. The primary endpoint was the change in AHI, with secondary endpoints including changes in body weight, hypoxic burden, sleep-related impairment, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure.

Results and Findings

The results from both trials were compelling. In trial 1, the mean change in AHI at week 52 was a reduction of 25.3 events per hour with tirzepatide, compared to a reduction of 5.3 events per hour with placebo, resulting in a treatment difference of -20.0 events per hour (95% CI, –25.8 to –14.2; P < .001). Similarly, trial 2 showed a reduction of 29.3 events per hour with tirzepatide versus 5.5 events per hour with placebo, yielding a treatment difference of -23.8 events per hour (95% CI, –29.6 to –17.9; P < .001). These reductions in AHI were statistically significant and clinically meaningful. Among the study participants treated with tirzepatide, 42.2% of those not using PAP therapy and 50.2% of those using PAP therapy achieved an AHI of fewer than five events per hour or between five and 14 events per hour, coupled with an Epworth Sleepiness Scale score of 10 or less, at the 52-week mark.

In the first trial, adults not using PAP and treated with tirzepatide experienced a 17.7% reduction in body weight at 52 weeks, compared to a 1.6% reduction in the placebo group (P < .001). In the second trial, adults using PAP and treated with tirzepatide lost 19.6% of their body weight, whereas those on placebo lost 2.3% (P < .001). 

Moreover, tirzepatide led to significant improvements in all prespecified key secondary endpoints. High-sensitivity C-reactive protein levels decreased by 40.1% in adults not using PAP and by 48.2% in those using PAP who were treated with tirzepatide, both of which were greater declines than those seen with placebo. Among adults not using PAP, the tirzepatide group experienced a 9.5 mm Hg reduction in systolic blood pressure compared to a 1.8 mm Hg decrease in the placebo group (P < .001). For adults using PAP, the tirzepatide group had a 7.6 mm Hg drop in systolic blood pressure, whereas the placebo group saw a 3.9 mm Hg decrease (P < .05). These findings underscore the dual efficacy of tirzepatide in managing both OSA and its associated metabolic and cardiovascular risks.

Among adults not using PAP therapy, 79.8% of those in the tirzepatide group and 76.7% in the placebo group experienced an adverse event. For those using PAP, 83.2% of the tirzepatide group and 72.8% of the placebo group reported adverse events. The most common adverse events were gastrointestinal in nature and were generally mild to moderate in severity.

Clinical Implications

The implications of these findings are profound. Tirzepatide offers a novel and effective treatment option for patients with OSA and obesity, potentially reducing the need for mechanical interventions like PAP therapy. The drug’s ability to address multiple aspects of metabolic health could lead to better patient adherence and outcomes, especially among those struggling with conventional treatments.

Furthermore, the significant reductions in inflammatory markers and blood pressure highlight tirzepatide’s potential to mitigate cardiovascular risks associated with OSA. This positions tirzepatide not only as a treatment for sleep apnea but also as a comprehensive approach to improving overall health in obese patients.

Continuous positive airway pressure (CPAP) therapy continues to be an effective treatment for OSA, but combining tirzepatide with CPAP could potentially be the optimal approach for improving OSA symptoms and reducing obesity-related cardiometabolic risk. 

Conclusion

The SURMOUNT-OSA trials mark a significant milestone in the treatment of obstructive sleep apnea and obesity. Tirzepatide’s robust efficacy in reducing AHI, promoting weight loss, and improving cardiovascular and inflammatory markers heralds a new era in managing these interrelated conditions. As we move forward, integrating such pharmacologic interventions into clinical practice could significantly enhance the quality of life for millions of patients worldwide, offering hope for a future where OSA and obesity are more effectively controlled.

Dr. Majety has no conflicts of interest to report.

Illustration by April Brust