Secondary outcomes from the SURMOUNT-OSA trial programme show that tirzepatide significantly improves multiple cardiometabolic risk factors in people with moderate-to-severe obstructive sleep apnoea (OSA) and obesity.¹ The findings suggest that the benefits are mediated through improvements in both body weight and OSA severity metrics.
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management and type 2 diabetes.
Methodology
The SURMOUNT-OSA programme (NCT05412004) included two 52-week, phase 3, randomised, double-blind, placebo-controlled studies.² Study 1 enrolled 234 participants with OSA and obesity who were not using positive airway pressure (PAP) therapy, while Study 2 enrolled 235 participants on established PAP therapy. Participants were randomised 1:1 to receive a once-weekly maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo. This prespecified analysis evaluated changes in key cardiometabolic risk measures.¹
Results
Compared with placebo, tirzepatide treatment led to significant improvements across most cardiometabolic markers. At week 48, the estimated treatment difference (ETD) for systolic blood pressure was –7.9 mmHg in Study 1 (p<0.001) and –4.3 mmHg in Study 2 (p=0.007). Diastolic blood pressure reduction was significant only in Study 1 (ETD: –3.2 mmHg; p=0.005).
At week 52, tirzepatide significantly reduced high-sensitivity C-reactive protein (hsCRP) in both Study 1 (ETD: –28.9%; p=0.003) and Study 2 (ETD: –45.1%; p<0.001). Significant improvements were also seen in lipid profiles, including increases in HDL-cholesterol and reductions in non-HDL-cholesterol and triglycerides in both studies (all p<0.001). Furthermore, tirzepatide led to substantial reductions in fasting insulin and homeostatic model assessment for insulin resistance (HOMA-IR) in both cohorts (all p<0.001).
A mediation analysis of the pooled data found that improvements in OSA metrics (apnoea–hypopnoea index and hypoxic burden) had a significant independent mediating effect on the reductions seen in hsCRP, HOMA-IR, and triglycerides.¹
In Practice
These results highlight that tirzepatide offers cardiometabolic benefits beyond weight loss alone in patients with OSA and obesity. The mediation analysis suggests a dual mechanism, where improvements in sleep-disordered breathing contribute independently to better metabolic and inflammatory profiles. According to the study investigators, "treating both sleep-disordered breathing and obesity is likely required to optimize the treatment effect on cardiometabolic benefits for patients with moderate-to-severe OSA and obesity."¹
Next Steps
The authors concluded that further research is needed to determine which specific patient populations with OSA are most likely to benefit from different therapeutic strategies.
This study was funded by Eli Lilly and Company.
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References
1. Malhotra A, Grunstein R, Azarbarzin A, et al. Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial. Nat Med (2026). https://doi.org/10.1038/s41591-025-04071-1
2. Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024;391:1193–1205. https://doi.org/10.1056/NEJMoa2404881