Empagliflozin's Ameliorating Effect on Plasma Triglycerides: Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease

J Atheroscler Thromb. 2020 Jul 1;27(7):644-656. doi: 10.5551/jat.50807. Epub 2019 Oct 18.


Aim: So far, the mechanisms behind the cardiovascular benefits of sodium/glucose cotransporter 2 (SGLT2) inhibitors have not been fully clarified.

Methods: In order to evaluate the effects of SGLT2 inhibitors on systemic hemodynamics, glucose metabolism, lipid profile, and endothelial function, 50 diabetic patients with established coronary artery disease (CAD) were included in this analysis and were given empagliflozin 10 mg/d. Cookie meal testing (carbohydrates: 75 g, fats: 28.5 g), endothelial function testing using flow-mediated dilatation (FMD), and body composition evaluation were performed before and after six months of treatment. Changes in %FMD between the treatment periods and its association with metabolic biomarkers were evaluated.

Results: After six months of treatment, the body weight and body fat percentage decreased significantly, while the body muscle percentage increased significantly. The hemoglobin A1c level and fasting and postprandial plasma glucose levels were significantly decreased with treatment. Postprandial insulin secretion was also significantly suppressed and the insulin resistance index was significantly decreased. Furthermore, the fasting and postprandial triglyceride (TG) levels decreased significantly, while total ketone bodies increased significantly after the six-month treatment. While the plasma brain natriuretic peptide level was not changed, the C-reactive protein level was decreased and FMD was significantly improved after the six-month treatment. Multiple regression analysis showed that the strongest predictive factor of FMD improvement is change in the plasma TG levels.

Conclusion: SGLT2 inhibitors improve multiple metabolic parameters. Of these, a reduction in plasma TGs was strongly associated with endothelial function recovery in diabetic patients with CAD, and this reduction may be related to the cardiovascular benefits of SGLT2 inhibitors.

Keywords: Diabetes mellitus; Endothelial function; Flow-mediated dilatation; Sodium/glucose transporter 2 inhibitors; Triglycerides.