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

Overview

Journal JAMA Intern Med

Publisher American Medical Association

Date 2025 Feb 10

PMID 39928303

Authors

Avik Ray

Julie M Paik

Deborah J Wexler

Sushama K Sreedhara

Katsiaryna Bykov

William B Feldman

Elisabetta Patorno

Affiliations

Soon will be listed here.

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.

References

Teltsch D, Farsani S, Swain R, Kaspers S, Huse S, Cristaldi C . Development and validation of algorithms to identify newly diagnosed type 1 and type 2 diabetes in pediatric population using electronic medical records and claims data. Pharmacoepidemiol Drug Saf. 2019; 28(2):234-243. DOI: 10.1002/pds.4728. View

Frieling K, Monte S, Jacobs D, Albanese N . Weight loss differences seen between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for treatment of type 2 diabetes. J Am Pharm Assoc (2003). 2021; 61(6):772-777. DOI: 10.1016/j.japh.2021.06.015. View

Polonsky W, Henry R . Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors. Patient Prefer Adherence. 2016; 10:1299-307. PMC: 4966497. DOI: 10.2147/PPA.S106821. View

Hernan M, Sauer B, Hernandez-Diaz S, Platt R, Shrier I . Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016; 79:70-75. PMC: 5124536. DOI: 10.1016/j.jclinepi.2016.04.014. View

Qiu M, Ding L, Zhan Z, Liu S . Use of SGLT2 inhibitors and occurrence of noninfectious respiratory disorders: a meta-analysis of large randomized trials of SGLT2 inhibitors. Endocrine. 2021; 73(1):31-36. DOI: 10.1007/s12020-021-02644-x. View

Albogami Y, Cusi K, Daniels M, Wei Y, Winterstein A . Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes. Diabetes Care. 2021; 44(6):1344-1352. PMC: 8247488. DOI: 10.2337/dc20-1794. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

Pradhan R, Lu S, Yin H, Yu O, Ernst P, Suissa S . Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study. BMJ. 2022; 379:e071380. PMC: 9623550. DOI: 10.1136/bmj-2022-071380. View

. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2023; 47(Suppl 1):S158-S178. PMC: 10725810. DOI: 10.2337/dc24-S009. View

10.

Ho T, Huang C, Ruan S, Tsai Y, Lai F, Yu C . Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality. PLoS One. 2017; 12(4):e0175794. PMC: 5391945. DOI: 10.1371/journal.pone.0175794. View

11.

Austin P . Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009; 28(25):3083-107. PMC: 3472075. DOI: 10.1002/sim.3697. View

12.

Hernan M, Hernandez-Diaz S . Beyond the intention-to-treat in comparative effectiveness research. Clin Trials. 2011; 9(1):48-55. PMC: 3731071. DOI: 10.1177/1740774511420743. View

13.

Ripollone J, Huybrechts K, Rothman K, Ferguson R, Franklin J . Implications of the Propensity Score Matching Paradox in Pharmacoepidemiology. Am J Epidemiol. 2018; 187(9):1951-1961. PMC: 6118075. DOI: 10.1093/aje/kwy078. View

14.

Wedzicha J, Banerji D, Chapman K, Vestbo J, Roche N, Ayers R . Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016; 374(23):2222-34. DOI: 10.1056/NEJMoa1516385. View

15.

Lipson D, Barnhart F, Brealey N, Brooks J, Criner G, Day N . Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018; 378(18):1671-1680. DOI: 10.1056/NEJMoa1713901. View

16.

Ahlbom A . Modern Epidemiology, 4th edition. TL Lash, TJ VanderWeele, S Haneuse, KJ Rothman. Wolters Kluwer, 2021. Eur J Epidemiol. 2021; 36(8):767-768. PMC: 8416883. DOI: 10.1007/s10654-021-00778-w. View

17.

Jacob C, Haas J, Bechtel B, Kardos P, Braun S . Assessing asthma severity based on claims data: a systematic review. Eur J Health Econ. 2016; 18(2):227-241. PMC: 5313583. DOI: 10.1007/s10198-016-0769-2. View

18.

Chen G, Lin Q, Zhuo D, Cui J . Elevated Blood Glucose is Associated with Severe Exacerbation of Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2022; 17:2453-2459. PMC: 9533778. DOI: 10.2147/COPD.S378259. View

19.

Rabe K, Celli B, Wechsler M, Abdulai R, Luo X, Boomsma M . Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Lancet Respir Med. 2021; 9(11):1288-1298. DOI: 10.1016/S2213-2600(21)00167-3. View

20.

Suissa S, DellAniello S, Ernst P . Comparative effectiveness of LABA-ICS versus LAMA as initial treatment in COPD targeted by blood eosinophils: a population-based cohort study. Lancet Respir Med. 2018; 6(11):855-862. DOI: 10.1016/S2213-2600(18)30368-0. View