Effects of SGLT2 Inhibitor on Ischemic Events Stemming From Atherosclerotic Coronary Diseases: A Systematic Review and Meta-analysis With Trial Sequential Analysis of Randomized Controlled Trials

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular complications of type-2 diabetes mellitus. However, the beneficial effects of SGLT2 inhibition are mainly associated with decline in hospitalization and death of heart failure. This systematic review will focus on the effect of SGLT2 inhibitors on ischemic events stemming from atherosclerotic coronary diseases, including angina pectoris, angina unstable, and myocardial infarction. We searched PubMed, Scopus, Embase, and Web of Science for relevant publications before October 2020. Twenty-two clinical trials consisting of 56,064 participants were included in the analysis. Cardiovascular effects following treatment with SGLT2 inhibitors were observed for angina pectoris, angina unstable, and myocardial infarction. A random-effects model was chosen, and after analysis of the P values and I2 statistic indices, we concluded that SGLT2 inhibitor treatment did not result in any significant differences in the incidence rate of angina pectoris [relative risk (RR), 0.98; 95% confidence interval (CI), 0.83-1.14; P = 0.92], angina unstable (RR, 0.95; 95% CI, 0.84-1.07; P = 0.84), or myocardial infarction (RR, 0.94; 95% CI, 0.79-1.11; P = 0.98) between the experimental and control groups with firm evidence from sensitivity and trial sequential analyses. This meta-analysis provides evidence that SGLT2 inhibitors have no significant effects on ischemic events stemming from atherosclerotic coronary diseases in patients with type-2 diabetes mellitus.