Metformin adherence and the risk of cardiovascular disease: a population-based cohort study

Shun-Fan Yu; Chien-Tai Hong; Wan-Ting Chen; Lung Chan; Li-Nien Chien

doi:10.1177/20406223231163115

Metformin adherence and the risk of cardiovascular disease: a population-based cohort study

Ther Adv Chronic Dis. 2023 Apr 4:14:20406223231163115. doi: 10.1177/20406223231163115. eCollection 2023.

Authors

Shun-Fan Yu¹, Chien-Tai Hong^{1

2

3}, Wan-Ting Chen⁴, Lung Chan^{5

2

3}, Li-Nien Chien^{6

7

8}

Affiliations

¹ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City.
² Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City.
³ Taipei Neuroscience Institute, Taipei Medical University, Taipei City.
⁴ Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, 291, Zhongzheng Rd, Zhonghe District, New Taipei City 23561.
⁶ Institute of Health and Welfare Policy, College of Medicine, National Yang-Ming Chiao Tung University, Taipei City. No.155, Sec. 2, Linong st., Beitou District, Taipei City 11221, Taiwan, R.O.C.
⁷ Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei City.
⁸ School of Health Care Administration, College of Management, Taipei Medical University, Taipei City.

Abstract

Background: Metformin is a potent antiglycemic agent, but its importance has receded owing to the launch of novel antidiabetic medications. The benefit of metformin includes not only blood sugar control but also anti-inflammation, autophagy activation, and neuroprotection. This study investigated the risk of cardiovascular disease (CVD) in people with type II diabetes mellitus (T2DM) who adhered to metformin after adding on a second-line antiglycemic agent.

Objectives: The purpose of this study was to investigate the benefits of metformin in CVD prevention in patients with T2DM.

Design: We designed the study by comparing the incident rate of CVD events in patients with T2DM who received metformin continually and who ceased metformin during 2002-2014.

Methods: Medical information was obtained from the National Health Insurance Research Database, and patients with T2DM receiving second-line antiglycemic agents were categorized into metformin-adherent and nonadherent groups according to prescription claims. The study outcomes were the incidence of CVD hospitalization, including stroke (ischemic and hemorrhagic) and myocardial infarction (MI).

Results: A total of 31,384 patients with T2DM constituted the metformin-adherent group and were 1:1 matched to nonadherent patients. Metformin adherence was associated with a lower risk of hospitalization due to stroke [adjusted hazard ratio (aHR) = 0.51, 95% confidence interval (CI): 0.43-0.59, p < 0.001] and MI (aHR = 0.47, 95% CI: 0.43-0.53, p < 0.001). The risk reduction persisted in both ischemic and hemorrhagic strokes. Our subgroup analysis revealed that the protective effect on stroke and MI hospitalization persisted in metformin-adherent patients, both sexes, patients aged ⩽65 or >65 years, and patients with or without concurrent insulin treatment.

Conclusions: This study revealed that metformin adherence in patients with T2DM who required a first-line treatment may reduce the risk of subsequent CVD. Despite the availability of numerous novel antiglycemic agents, metformin adherence by patients who require a combination of antiglycemic agents provides an additional benefit of CVD protection.

Keywords: cardiovascular disease; diabetes; metformin; myocardial infarction; stroke.