Abstract Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently demonstrated efficacy in reducing apnea-hypopnea index in obesity-associated sleep apnea and exert systemic anti-inflammatory and cardiometabolic benefits. Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, frequent exacerbations, and high cardiovascular burden, which are further amplified in patients with concomitant obstructive sleep apnea (OSA). Given these intersecting pathophysiologic pathways, we evaluated whether GLP-1 RA use is associated with improved respiratory and cardiovascular outcomes in patients with COPD and OSA receiving continuous positive airway pressure (CPAP) therapy. Methods Using the TriNetX Research Network (queried February 22, 2025), we identified adults (≥18 years) with COPD (ICD-10 J44*) and OSA documented between January 1, 2020, and January 1, 2024, with evidence of CPAP use. Patients prescribed a GLP-1 RA with verified medication adherence were compared with those not receiving a GLP-1 RA. Propensity score matching (1:1) was performed using 48 demographic and clinical covariates, including age, sex, race, BMI, smoking status, comorbidities, and concomitant cardiometabolic medications, to balance baseline differences. Primary outcomes were COPD exacerbations, glucocorticoid use, and all-cause mortality at 12 months. Secondary outcomes included cardiovascular events, heart failure exacerbations, and intensive care unit (ICU) admissions. Results Before matching, GLP-1 RA users exhibited greater cardiometabolic comorbidity burdens, including diabetes (90.1% vs. 50.8%), hypertension (88.5% vs. 73.2%), and obesity (16.6% vs. 3.6%), with higher mean BMI (41.2 ± 9.1 vs. 35.8 ± 9.3 kg/m²; p 0.001). After matching, 8,935 patients remained in each cohort with well-balanced baseline features. At one year, GLP-1 RA users demonstrated significantly lower rates of COPD exacerbations (24.3% vs. 30.8%; OR 0.71, 95% CI 0.67-0.76), systemic glucocorticoid use (48.5% vs. 53.4%; OR 0.82, 95% CI 0.77-0.86), and all-cause mortality (7.8% vs. 16.9%; OR 0.42, 95% CI 0.38-0.46; p 0.01). Cardiovascular outcomes also favored the GLP-1 cohort, with fewer heart failure exacerbations (20.6% vs. 27.7%; OR 0.67, 95% CI 0.63-0.72) and acute coronary events (6.1% vs. 7.3%; OR 0.82, 95% CI 0.73-0.93). ICU admission rates were markedly lower (16.5% vs. 25.5%; OR 0.57, 95% CI 0.53-0.62). Discussion In this large, real-world cohort of patients with COPD and OSA on CPAP therapy, GLP-1 RA use was associated with fewer respiratory exacerbations, improved cardiovascular outcomes, reduced healthcare utilization, and significantly lower mortality. These findings support the potential multidimensional benefits of GLP-1 RAs in the COPD-OSA overlap population and warrant prospective randomized evaluation to confirm causality and elucidate underlying mechanisms. This abstract is funded by: none
Gupta et al. (2026) studied this question.