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

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.

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.

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.

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.