Association of GLP-1 Receptor Agonists with Chronic Obstructive Pulmonary Disease Exacerbations among Patients with Type 2 Diabetes

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) have worse clinical outcomes compared with patients without metabolic dysregulation. GLP-1 (glucagon-like peptide 1) receptor agonists (GLP-1RAs) reduce asthma exacerbation risk and improve FVC in patients with COPD. Objectives: To determine whether GLP-1RA use is associated with reduced COPD exacerbation rates, and severe and moderate exacerbation risk, compared with other T2D therapies. Methods: A retrospective, observational, electronic health records-based study was conducted using an active comparator, new-user design of 1,642 patients with COPD in a U.S. health system from 2012 to 2022. The COPD cohort was identified using a previously validated machine learning algorithm that includes a natural language processing tool. Exposures were defined as prescriptions for GLP-1RAs (reference group), DPP-4 (dipeptidyl peptidase 4) inhibitors (DPP-4is), SGLT2 (sodium-glucose cotransporter 2) inhibitors, or sulfonylureas. Measurements and Main Results: Unadjusted COPD exacerbation counts were lower in GLP-1RA users. Adjusted exacerbation rates were significantly higher in DPP-4i (incidence rate ratio, 1.48 [95% confidence interval, 1.08-2.04]; P = 0.02) and sulfonylurea (incidence rate ratio, 2.09 [95% confidence interval, 1.62-2.69]; P, 0.0001) users compared with GLP-1RA users. GLP-1RA use was also associated with significantly reduced risk of severe exacerbations compared with DPP-4i and sulfonylurea use, and of moderate exacerbations compared with sulfonylurea use. After adjustment for clinical covariates, moderate exacerbation risk was also lower in GLP-1RA users compared with DPP-4i users. No statistically significant difference in exacerbation outcomes was seen between GLP-1RA and SGLT2 inhibitor users. Conclusions: Prospective studies of COPD exacerbations in patients with comorbid T2D are warranted. Additional research may elucidate the mechanisms underlying these observed associations with T2D medications.