Effectiveness of GLP-1 receptor agonists to prevent obstructive sleep apnea in patients with type 2 diabetes: active comparator, new user cohort study.

Abstract

Obstructive sleep apnea (OSA) is highly prevalent in type 2 diabetes (T2D), sharing metabolic risk factors, notably obesity, and increased cardiovascular outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce OSA severity in clinical trials but their role in preventing incident OSA in T2D remains unclear. To assess whether GLP-1RA use is associated with a reduced risk of incident OSA compared with dipeptidyl peptidase-4 inhibitors (DPP-4i), a weight-neutral comparator, in patients with T2D. We conducted a population-based cohort study using the UK CPRD (2007-2023) database with an active-comparator, new-user design. Adults with T2D and BMI ≥30 kg/m² initiating a GLP-1RA or DPP-4i were included, excluding individuals with prior sleep apnea. Propensity scores with fine-stratification weighting were used within BMI strata. The primary outcome was incident clinical diagnosis of OSA. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using an as-treated approach, with up to 3 years of follow-up. The cohort included 47,315 GLP-1RAs and 159,066 DPP-4i initiators with baseline characteristics well balanced after weighting. During follow-up, 612 and 1,197 incident OSA cases occurred among GLP-1RAs and DPP-4i users, yielding incidence rates of 5.8 and 5.4 per 1000 person-years, respectively. The HR of incident OSA with GLP-1RA use compared with DPP-4i use was 1.07 (95% CI 0.93-1.23). Results were consistent across BMI strata, sex, drug type, and multiple sensitivity analyses. In routine clinical care, GLP-1RAs were not associated with a decreased incidence of OSA in patients with T2D and no history of OSA, when compared with DPP-4i.