Glucagon-like peptide-1 (GLP-1) receptor agonists appear to reduce mortality in people with type 2 diabetes (T2DM). A new study of nearly 1.8 million patients reports that people with both type 2 diabetes and obstructive sleep apnea (OSA) derive greater survival benefit from GLP-1 receptor agonist therapy than those who have T2DM but not OSA.
This finding suggests that OSA status may enhance the mortality benefit of GLP-1 receptor agonist therapy by acting as an effect modifier in the association between GLP-1 receptor agonist prescription and death.
Type 2 diabetes (T2DM) is a chronic metabolic condition that can lead to cardiovascular complications and increased mortality risk. GLP-1 receptor agonists such as semaglutide, tirzepatide, and dulaglutide reduce cardiovascular and all-cause mortality in people with T2DM, but their effects in those who also have OSA are unclear.
Real-World Study Data
The researchers built on the results of the SURMOUNT-OSA1 trial, which showed tirzepatide’s efficacy in improving OSA in non-diabetic patients. They examined whether OSA affects the mortality benefit associated with GLP-1RA use in people with T2DM in a large, real-world population.
The investigators identified 1,799,261 patients with T2DM who were prescribed metformin, and it determined all-cause mortality within 1year of metformin, with or without a GLP-1 receptor agonist prescription. Propensity score matching, adjusted for demographics and comorbidities, and Cochran-Mantel-Haenszel testing were used to assess effect modification by OSA status.
The study analyzed four groups: 1,083,492 patients (60.2%) had neither OSA diagnosis nor GLP-1 receptor agonist prescription; 361,49 (20.1%) were prescribed a GLP-1 receptor agonist without an OSA diagnosis; 207,947(11.6%) were diagnosed with OSA but did not have a GLP-1 receptor agonist prescription; and 146,330 (8.1%) were diagnosed with OSA and prescribed a GLP-1 receptor agonist.
Semaglutide was the most prescribed GLP-1 receptor agonist, followed by dulaglutide and tirzepatide.
One-year mortality in patients with type 2 diabetes who received GLP-1RAs prescriptions was substantially lower than in those who were not prescribed GLP-1RAs, with a disproportionate benefit found in those who were also diagnosed with OSA.
Following propensity score matching, with standardized mean differences (P<0.001), the relative risk of mortality for OSA patients compared with non-OSA patients was 1.2, indicating that OSA conferred a 20% greater mortality benefit. The Cochran-Mantel-Haenszel statistic was significant (P<0.001).
The 20% greater relative mortality decrease in patients with OSA support considering OSA status when prescribing GLP-1 receptor agonists, the researchers note. They also advise future research to examine the relationship between OSA and T2DM diagnosis, as well as the long-term outcomes of GLP-1 receptor agonist therapy.
Reference
Fowler C, Bliwise D, Collop 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. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
