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Comment
. 2025 Apr 1;185(4):399-410.
doi: 10.1001/jamainternmed.2024.7811.

Glucose-Lowering Medications and Risk of Chronic Obstructive Pulmonary Disease Exacerbations in Patients With Type 2 Diabetes

Avik Ray  1 , Julie M Paik  1   2   3 , Deborah J Wexler  4 , Sushama K Sreedhara  1 , Katsiaryna Bykov  1 , William B Feldman  1   5 , Elisabetta Patorno  1
Affiliations
Comment

Glucose-Lowering Medications and Risk of Chronic Obstructive Pulmonary Disease Exacerbations in Patients With Type 2 Diabetes

Avik Ray et al. JAMA Intern Med. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wexler reported service on the data monitoring committee for Novo Nordisk outside the submitted work. Dr Bykov reported grants from the National Institutes of Health during the conduct of the study. Dr Feldman reported grants from the National Institutes of Health during the conduct of the study as well as personal fees from Alosa Health and service as an expert witness in litigation against inhaler manufacturers outside the submitted work. Dr Patorno reported grants from the National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, US Food and Drug Administration, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

Comment on

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