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

Abstract

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