Glucose-Lowering Medications and Risk of Chronic Obstructive Pulmonary Disease Exacerbations in Patients With Type 2 Diabetes
Authors: Avik Ray, Julie M. Paik, Deborah J. Wexler, Sushama K. Sreedhara, Katsiaryna Bykov, William B. Feldman, Elisabetta Patorno
Journal: JAMA Internal Medicine (2025)

Importance Recent studies have suggested that sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) may benefit patients with chronic obstructive pulmonary disease (COPD). However, clinical evidence is lacking on their comparative association with COPD exacerbations in US patients with type 2 diabetes (T2D). Objective To compare the risk of moderate or severe COPD exacerbations among SGLT-2is, GLP-1RAs, and DPP-4is. Design, Setting, and Participants This comparative effectiveness research study used data from three 1:1 propensity score–matched cohort studies that emulated 3 target trials comparing patients 40 years or older with T2D and active COPD who initiated treatment with SGLT-2is vs DPP-4is, GLP-1RAs vs DPP-4is, and SGLT-2is vs GLP-1RAs. Data were from 3 US insurance claims databases: the Optum deidentified Clinformatics Data Mart Database (2013-2023), IBM Health MarketScan (2013-2021), and Medicare fee for service (2013-2020). The data analysis was conducted from January to June 2024. Exposures Initiation of SGLT-2i or DPP-4i, GLP-1RA or DPP-4i, and SGLT-2i or GLP-1RA for the 3 target trials, respectively. Main Outcomes and Measures First occurrence of a moderate or severe COPD exacerbation, defined as a filled prescription for oral glucocorticoids in association with an outpatient COPD visit or hospitalization for COPD. Incidence rates, incidence rate differences (IRDs), and hazard ratios (HRs) with 95% CIs were calculated. Results There were 27 991, 32 107, and 36 218 pairs in the SGLT-2i vs DPP-4i, GLP-1RA vs DPP-4i, and SGLT-2i vs GLP-1RA propensity score–matched cohorts, respectively (mean [SD] age, 70.8 [8.6] and 70.7 [8.8], 70.4 [8.5] and 70.4 [8.2], and 69.8 [8.7] years, respectively; 13 767 [49.2%] and 13 847 [49.5%], 17 622 [54.9%] and 17 620 [54.9%], and 18 807 [51.9%] and 18 854 [52.1%] female individuals, respectively). During a median follow-up of 145 (IQR, 61-355) days of treatment, the risk of moderate or severe COPD exacerbation was lower among those treated with SGLT-2is vs DPP-4is (9.26 vs 11.4 per 100 person-years [PYs]; HR, 0.81; 95% CI, 0.76-0.86; IRD/100 PYs, −2.20; 95% CI, −2.83 to −1.58) and among those treated with GLP-1RAs vs DPP-4is (9.89 vs 11.49 per 100 PYs; HR, 0.86; 95% CI, 0.81-0.91; IRD/100 PYs, −1.60; 95% CI, −2.18 to −1.02), with minimal differences among those treated with SGLT-2is vs GLP-1RAs (9.47 vs 10.00 per 100 PYs; HR, 0.94; 95% CI, 0.89-1.00; IRD/100 PYs, −0.55; 95% CI, −1.09 to −0.01). Results were consistent across sensitivity and subgroup analyses. Conclusions and Relevance The results of this comparative effectiveness research study suggest that SGLT-2is and GLP-1RAs were associated with a reduced risk of moderate or severe COPD exacerbations compared with DPP-4i in adults with T2D and active COPD. This may inform prescribing of glucose-lowering medications among patients with T2D and active COPD.