Empagliflozin Ameliorating Effect of on Plasma Triglyceride: An Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease

Abstract

Introduction: The mechanisms behind the cardiovascular benefits of Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have not been fully clarified. We aimed to identify potential mechanisms underlying the favorable effects of SGLT2 inhibitors on cardiovascular events. Methods: The 50 diabetic patients with established Coronary Artery Disease (CAD) included in this study analysis were administered 10 mg/day of empagliflozin. Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g), endothelial function testing using Flow-Mediated Dilatation (FMD), and body composition evaluation were performed before and after 6 months treatments. Evaluation of changes in % FMD between treatment periods, and its association with metabolic biomarkers were evaluated. Results: After the 6 month treatment, body weight and body fat percentage decreased significantly, while body muscle percentage increased significantly. HbA1C level and fasting and postprandial plasma glucose levels were significantly decreased by treatment. Postprandial insulin secretion was also significantly suppressed and insulin resistance index was significantly decreased. Furthermore, fasting and postprandial triglyceride levels decreased significantly while total ketone body increased significantly after the 6 months treatment. While plasma brain natriuretic peptide level was not changed, C-reactive protein was decreased, and FMD was significantly improved after the 6 months treatment. Multiple regression analysis showed the strongest predictive factor of FMD improvement to be change in fasting and postprandial plasma triglyceride levels. Conclusion: SGLT2 inhibitors improved multiple metabolic parameters. Of these, reduction in plasma triglyceride was strongly associated with endothelial function recovery in diabetic patients with CAD, and this reduction may be related to the cardiovascular benefit of SGLT2 inhibitors.