Association of novel antihyperglycemic drugs versus metformin with decrease in asthma exacerbations

Yuya Kimura; Taisuke Jo; Norihiko Inoue; Maho Suzukawa; Yohei Hashimoto; Ryosuke Kumazawa; Miho Ishimaru; Hiroki Matsui; Akira Yokoyama; Goh Tanaka; Yusuke Sasabuchi; Hideo Yasunaga

doi:10.1016/j.jaip.2024.05.002

Association of novel antihyperglycemic drugs versus metformin with decrease in asthma exacerbations

J Allergy Clin Immunol Pract. 2024 May 9:S2213-2198(24)00467-7. doi: 10.1016/j.jaip.2024.05.002. Online ahead of print.

Authors

Yuya Kimura¹, Taisuke Jo², Norihiko Inoue³, Maho Suzukawa⁴, Yohei Hashimoto⁵, Ryosuke Kumazawa⁶, Miho Ishimaru⁷, Hiroki Matsui⁸, Akira Yokoyama⁹, Goh Tanaka¹⁰, Yusuke Sasabuchi¹¹, Hideo Yasunaga¹²

Affiliations

¹ Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan; Clinical Research Center, National Hospital Organization Tokyo Hospital, Tokyo, Japan. Electronic address: yuk.close.to.wrd.34@gmail.com.
² Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: jo.taisuke@gmail.com.
³ Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan; Department of Clinical Data Management and Research, Clinical Research Center, National Hospital Organization Headquarters, Tokyo, Japan. Electronic address: noricom.tmdu@gmail.com.
⁴ Clinical Research Center, National Hospital Organization Tokyo Hospital, Tokyo, Japan. Electronic address: fueta-tky@outlook.jp.
⁵ Save Sight Institute, The University of Sydney, Sydney, Australia. Electronic address: yohashimoto1223@gmail.com.
⁶ Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: rkumazawa84@gmail.com.
⁷ Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan; Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: ishimaru.ohp@tmd.ac.jp.
⁸ Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: ptmatsui-tky@g.ecc.u-tokyo.ac.j.
⁹ Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: che.vartan@gmail.com.
¹⁰ Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: gtanaka.tky@gmail.com.
¹¹ Department of Real-world Evidence, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: rhapsody77777@gmail.com.
¹² Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: yasunagah@m.u-tokyo.ac.jp.

PMID: 38734374
DOI: 10.1016/j.jaip.2024.05.002

Abstract

Background: Similar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism.

Objective: To investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes.

Methods: Using a Japanese national administrative database, we constructed three active comparators-new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids.

Results: DPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs. 17.4 per 100 person-years; hazard ratio 1.09, 1.05 to 1.14; GLP-1 RAs: 24.9 vs. 19.0 per 100 person-years; 1.14, 1.01 to 1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs. 18.1 per 100 person-years; hazard ratio 1.00, 0.97 to 1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs. 56.6 per 100 person-years; rate ratio 0.95, 0.91 to 0.99).

Conclusions: While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

Keywords: Asthma; Dipeptidyl peptidase-4 inhibitors; Glucagon-like peptidase 1 receptor agonists; Metformin; National administrative database; Sodium glucose co-transporter-2 inhibitors; Type 2 diabetes.