Association Between Glucagon-Like Peptide-1 Receptor Agonists and Clinical Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obesity

Background: Chronic obstructive pulmonary disease (COPD) frequently coexists with obesity, creating a vulnerable phenotype associated with increased exacerbations and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated benefits in weight management and cardiovascular protection, but their effects in patients with COPD and obesity remain unclear. Methods: We conducted a retrospective cohort study using the TriNetX global research network. We identified adult patients with coexisting COPD and obesity who initiated GLP-1RA or other weight-loss medications. We performed 1:1 propensity-score matching to balance baseline characteristics between the study groups. The primary outcome was all-cause mortality. Secondary outcomes included COPD exacerbations, acute respiratory failure, pneumonia, and major adverse cardiovascular events (MACE). Results: After propensity score matching, the study included 10,487 patients in each group. During follow-up, all-cause mortality occurred in 237 patients (0.8 per 100 person-years) in the GLP-1RA group compared with 519 patients (2.2 per 100 person-years) in the control group (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.37 to 0.50). GLP-1RA use was also associated with reduced risk of COPD exacerbations (HR, 0.79; 95% CI, 0.71 to 0.88), acute respiratory failure (HR, 0.55; 95% CI, 0.49 to 0.62), pneumonia (HR, 0.72; 95% CI, 0.64 to 0.81), and MACE (HR, 0.71; 95% CI, 0.64 to 0.79). Results remained consistent across multiple sensitivity analyses and subgroup analyses. Conclusion: Among patients with coexisting COPD and obesity, GLP-1RA use was associated with lower risks of mortality and adverse respiratory and cardiovascular outcomes compared with other weight loss medication. However, given the observational nature of this study, these findings should be interpreted with caution, as residual confounding cannot be excluded. Randomized controlled trials are warranted to establish causality and confirm these findings.