Sleep Apnea Significantly Impacts Mortality Benefit of GLP-1s

Patients with type 2 diabetes (T2D) and comorbid obstructive sleep apnea (OSA) experience a 20% greater mortality benefit at 1 year when prescribed a GLP-1 receptor agonist compared to patients without OSA who are also prescribed the drug class.

The new findings, presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago, IL, this week, suggest the increasingly common OSA diagnosis may be an effect modifier in the link between mortality benefit and GLP-1 receptor agonists. Investigators led by Cosmo Fowler, MD, hypothesized that an OSA diagnosis may help to identify patients with T2D who will derive better mortality benefit from the drug class.

Fowler and colleagues conducted a meta-analysis of nationally-spanning claims and electronic health record (EHR) data to compare the impact of OSA diagnoses on mortality outcomes in patients with T2D prescribed any combination of metformin and/or GLP-1 receptor agonists.

“While SURMOUNT-OSA showed significant improvement in non-diabetes-associated OSA following [GLP-1 receptor agonist] tirzepatide administration and the mortality benefit of GLP-1 receptor agonists is well-established in patients with T2D, whether OSA modifies outcomes in T2D patients receiving GLP-1 receptor agonists is unknown," investigators wrote.

What was established in SURMOUNT-OSA?

The phase 3 SURMOUNT-OSA trial assessed the efficacy and safety of 10 or 15 mg tirzepatide (Zepbound) in patients with OSA over 52 weeks. Investigators — led by Atul Malhotra, a board-certified pulmonologist and University of California, San Diego sleep medicine specialist — found patients receiving tirzepatide achieved a mean ≤20% weight loss and ≥25 fewer breathing interruptions per hour slept (P <.001).

Malhotra and colleagues also found tirzepatide was associated with significantly improved apnea-hypopnea index (AHI) scores, as well as improved blood pressure and C-reactive protein levels, among other secondary outcomes.

In an interview with HCPLive, Malhotra noted that while continuous positive airway pressure (CPAP) remains the first-line therapy for sleep apnea, the clinical and specifically bariatric effect of tirzepatide makes it a “reasonable option” for patients who cannot or will not use a CPAP machine for their OSA.

“The data suggest if you can treat either obesity or sleep apnea or both, it's better [to] treat both, rather than either condition alone,” Malhotra said.

What is the effect of OSA on T2D-related mortality?

OSA is highly prevalent and potentially detrimental to patients with T2D. In fact, most patients with T2D are also diagnosed with comorbid OSA, which significantly increases cardiovascular event and related mortality risks.

A 2024 retrospective cohort analysis reported that a diagnosis of both T2D and OSA increased the likelihood of all-cause mortality by 52% versus lone OSA (hazard ratio [HR], 1.52; 95% CI, 1.48 – 1.57).

How do patients with OSA and T2D benefit from GLP-1 receptor agonists?

Fowler and colleagues analyzed approximately 1.8 million patients in the US with T2D who were prescribed metformin between October 2015 and April 2025. Their 4 cohorts included:

• 1,083,492 (60.2%) patients with neither OSA nor a GLP-1 prescription
• 361,492 (20.1%) patients without OSA, but a GLP-1 prescription
• 207,947 (11.6%) patients with OSA, but no GLP-1 prescription
• 146,330 (8.1%) patients with OSA and a GLP-1 prescription

The most prescribed GLP-1 receptor agonist was semaglutide, followed by dulaglutide then tirzepatide.

After propensity score-matching for demographic and clinically relevant comorbidity data, the investigators found that patients without OSA but with a GLP-1 prescription achieved a doubly improved one-year all-cause mortality benefit compared with non-OSA patients who did not receive a GLP-1 prescription (relative risk [RR], 2.04; 95% CI, 1.95 – 2.13; P <.001).

Among patients with OSA, the one-year mortality benefit between those who did and did not receive a GLP-1 prescription was even greater (RR, 2.45; 95% CI, 2.29 – 2.61; P <.001). The ratio of relative risks for mortality between the non-OSA and OSA cohorts was 1.2 — indicating a 20% greater mortality benefit with GLP-1 receptor agonists for patients with T2D and OSA (P < .001).

What do these findings mean for practice?

Fowler said in a press release accompanying the new data at CHEST 2025 that their findings suggest that “OSA status may act as an effect modifier on the association between GLP-1 receptor agonist prescription and mortality.”

The 20% greater impact on relative mortality reduction among patients with both T2D and OSA encourages clinicians to consider their patients’ sleep apnea status when deciding whether to prescribe GLP-1. That said, future analyses may need to better elucidate the relationship between OSA, T2D, and long-term outcomes with GLP-1 receptor agonists.

References

1. Fowler C, Bliwise D, Collap NA. Enhanced Survival Benefit for GLP-1 Receptor Agonist Prescription in Patients with Coexisting Type 2 Diabetes and Sleep Apnea: A Real-World Analysis Of 1.8 Million Patients. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.
2. Malhotra A, Derman C. Tirzepatide’s Impact on OSA, With Atul Malhotra, MD. HCPLive. Published September 29, 2025. https://www.hcplive.com/view/tirzepatide-impact-on-osa-atul-malhotra-md
3. Malik JA, Masoodi SR, Shoib S. Obstructive sleep apnea in Type 2 diabetes and impact of continuous positive airway pressure therapy on glycemic control. Indian J Endocrinol Metab. 2017;21(1):106-112. doi:10.4103/2230-8210.196005
4. Riley DR, Henney A, Anson M, et al. The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes. Diabetes Obes Metab. 2025;27(2):663-674. doi:10.1111/dom.16059