Associations Between Glucagon-like Peptide-1 Receptor Agonists and Respiratory Outcomes in Chronic Obstructive pulmonary disease and Diabetes.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently complicated by acute respiratory failure, pneumonia, exacerbations, and premature mortality, particularly in patients with comorbid type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) possess anti-inflammatory and metabolic properties that may confer protective effects against COPD-related respiratory complications, but comparative evidence remains limited. METHODS: We conducted a retrospective cohort study using data from the TriNetX global federated health research network. Adults aged 40 years or older with both COPD and T2D who newly initiated GLP-1RAs, dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), or metformin between January 1, 2017, and May 31, 2025, were identified. An active-comparator, new-user design with 1:1 propensity score matching was applied. The primary outcome was incident acute respiratory failure. Secondary outcomes included all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia, assessed over one year of follow-up. RESULTS: After propensity score matching, GLP-1RA use was associated with significantly lower risk of acute respiratory failure compared with DPP-4is (HR, 0.77; 95% CI, 0.73-0.81), SUs (HR, 0.80; 95% CI, 0.76-0.84), and metformin (HR, 0.91; 95% CI, 0.85-0.98). GLP-1RA use was also consistently associated with reduced risks of all-cause mortality, all-cause hospitalization, acute exacerbation of COPD, and pneumonia across all three comparator groups. Subgroup analyses demonstrated consistent protective trends across sex, age, exacerbation history, and inhaled bronchodilator regimen. CONCLUSIONS: In patients with COPD and T2D, initiation of GLP-1RAs was associated with significantly lower risks of acute respiratory failure, pneumonia, acute exacerbation, hospitalization, and all-cause mortality compared with DPP-4is, SUs, and metformin. These findings suggest that GLP-1RA therapy may offer meaningful respiratory and survival benefits in this high-risk population.