Abstract Background Obesity contributes to worse symptoms and exacerbations in chronic obstructive pulmonary disease (COPD). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve weight and metabolic profiles and have emerging pulmonary benefits. However, their real-world impact on respiratory outcomes in patients with COPD and obesity is not well established. Research Question Among obese adults with COPD, is GLP-1 RA use associated with reduced risk of COPD exacerbations, acute respiratory failure, and all-cause mortality compared with those not receiving GLP-1 therapy? Methods We conducted a retrospective, propensity-matched cohort study using the TriNetX U.S. Collaborative Network. Adults aged ≥40 years with COPD (ICD-10 J44) and BMI ≥30 kg/m² were included. The exposed cohort comprised patients prescribed GLP-1 RAs (lixisenatide, albiglutide, dulaglutide, liraglutide, semaglutide, or exenatide), while comparators had no exposure. The index event was the first date meeting inclusion criteria. Outcomes were analyzed beginning 180 days after index to minimize reverse causation, excluding those with prior events. Propensity score matching (1:1) balanced demographics, comorbidities, laboratory data, and medication use, yielding 2,795 patients per group. Primary outcomes included the risk (≥1 event within window) of COPD exacerbation, acute respiratory hypoxic and/or hypercapnic failure leading to hospitalization, and all-cause mortality. Risk difference (RD), risk ratio (RR), and odds ratio (OR) were calculated; Kaplan-Meier and log-rank testing assessed time-to-event. Results After matching, baseline characteristics were well balanced. GLP-1 RA use was associated with significantly lower risk across all outcomes:COPD Exacerbation (J44.1): 18.2% (No GLP-1) vs 11.2% (GLP-1); RD 7.0%, RR 1.63 (95% CI 1.36-1.94); p = 0.042.Acute Hypoxic and/or Hypercapnic Respiratory Failure (J96.x): 19.2% vs 11.5%; RD 7.7%, RR 1.67 (1.42-1.96).All-Cause Mortality: 14.6% vs 7.6%; RD 7.0%, RR 1.92 (1.64-2.25); p = 0.010. Kaplan-Meier survival analysis demonstrated significantly improved survival in the GLP-1 group for mortality and COPD exacerbation outcomes. Conclusions In obese adults with COPD, GLP-1 RA therapy was associated with clinically and statistically significant reductions in COPD exacerbations, acute respiratory failure, and all-cause mortality. These findings suggest that GLP-1 RAs may offer dual metabolic and pulmonary benefits and warrant evaluation as adjunctive therapy in future prospective trials. This abstract is funded by: None
Lohana et al. (Fri,) studied this question.