Therapeutic Effects of Empagliflozin in Diabetic Patients After Acute Myocardial Infarction: Systematic Review and Meta-Analysis With Trial Sequential Analysis

Introduction: Empagliflozin is a new sodium-glucose transporter protein 2 (SGLT2) inhibitor. In addition to its anti-hyperglycemic effect, recent studies suggested that it may improve cardiac outcomes in diabetic patients with acute myocardial infarction. This systematic review and meta-analysis aims to test this hypothesis. Methods: We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science. We included studies comparing empagliflozin versus placebo in diabetic patients with acute myocardial infarction. Our outcomes were the changes in plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), left ventricular ejection fraction% (LVEF%), and hemoglobin A1c (HbA1c) levels. We performed Trial Sequential Analysis (TSA), and we used mean difference (MD) and 95% confidence interval (CI) as our effect size with a random effects model. Results: Five studies (one cohort study and four randomized controlled trials), compromising 751 patients, were included. Empagliflozin significantly increased LVEF compared to placebo (MD = 1.80, 95% CI [0.50, 3.10], P =0.007), however, the TSA curve did not cross the conventional boundary for statistical significance, indicating that the available evidence did not reach the predetermined threshold. On the other hand, we observed no significant difference between the two groups in terms of NT-pro-BNP and HbA1c (MD = -136.59, 95% CI [-293.43, 20.25], P =0.09; MD= -0.72, 95% CI [-1.73, 0.29], P =0.16, respectively). Conclusions: Our meta-analysis reveals that among diabetic patients with acute myocardial infarction, empagliflozin failed to improve cardiac parameters such as LVEF and NT-pro-BNP without providing additional benefits in reducing HbA1c levels. Therefore further large-scale RCTs are warranted to ascertain our findings.