Association between glucagon-like peptide-1 receptor agonist therapy and respiratory illness in patients with type 2 diabetes: a retrospective observational cohort study

Studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide lung benefits beyond glycemic control, including reduced risks of lung malignancy, pulmonary infection and chronic obstructive pulmonary disease exacerbations. A retrospective cohort study with a new-user and active-comparator design was conducted using the TriNetX US Network. Adults (≥ 18 years) with Type 2 diabetes mellitus (T2DM) ( n = 3,389,059) from January 1, 2005, to December 31, 2020, were identified. Two cohorts of new GLP-1 RA ( n = 201,153) and new dipeptidyl peptidase-4 inhibitor (DPP4i) ( n = 323,114) users were created. Propensity score matching was used to create comparable cohorts. The primary outcome was lung cancer, while other pulmonary conditions were secondary outcomes over a 10-year follow-up. Through 1:1 propensity score matching, two balanced cohorts of GLP-1 RA and DPP4i ( n = 158,224) users were created. GLP-1 RA users had a significantly lower risk of lung cancer than did DPP4i users (hazard ratios [HR] 0.86; 95% confidence interval [CI] 0.80–0.94). Reduced risk of influenza and pneumonia (HR 0.94; 95% CI 0.92–0.96) and pulmonary fibrosis (HR 0.92; 95% CI 0.87–0.98) were also noted in GLP-1 RA users. Our findings indicate that GLP-1 RAs may lower the risks of lung cancer, pulmonary fibrosis, and respiratory infections, meriting further prospective study.