Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study

Abstract

Background : Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcome and death from any cause. While treatment with sulfonylurea reduces microvascular complications in diabetes, it increases cardiovascular hospitalization or mortality in combination with metformin. In the present study, we assessed the effects of empagliflozin and glimepiride, a commonly prescribed sulfonylurea, on endothelial function using flow–mediated dilation (FMD) to estimate arteriosclerosis and cardiovascular events in patients with type 2 diabetes. Methods : In this prospective, open-label, randomized, parallel-group study, 58 patients with type 2 diabetes received metformin and glargine before bedtime for 12 weeks. This was followed by additional treatment with either 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), measured prior to and after 12 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. Results : Analysis of the empagliflozin group ( n = 30) and glimepiride group ( n = 28) showed no significant differences in DFMDs (empagliflozin, −0.19 ± 2.34%; glimepiride, −0.37 ± 2.77%; P = 0.79). Similarly, changes in glycated hemoglobin (HbA1c) were similar between the two groups. However, significant difference in body weight changes were observed between the two groups (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). In addition, an analysis of the body composition revealed that body fluid volume significantly decreased after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, –0.33 ± 0.72 L; P = 0.03). Conclusions : Empagliflozin did not improve endothelial function when compared to glimepiride in patients with type 2 diabetes but decreased their body fluid volume. This suggested that the coronary protective effect of empagliflozin is not derived by protection of the endothelial function but rather from reduction in the risk of heart failure. Trial Registration : This trial was registered on September 13, 2016; UMIN000024001 . Keywords: Empagliflozin, Endothelial function, Glimepiride, Diabetes, Flow–mediated dilation