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

Background: Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes and death from any cause. Alternatively, treatment with sulfonylurea reduces microvascular complications in diabetes but appears to increase cardiovascular hospitalization or mortality in combination with metformin. Therefore, in the present study, we assessed the effects of empagliflozin and glimepiride, a 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 comparison, 58 patients with type 2 diabetes were administered metformin and glargine before bedtime for 12 weeks, followed by the random addition of 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), which was measured prior to and following 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). Likewise, glycated hemoglobin (HbA1c) changes were similar between the two groups. Body weight changes significantly differed (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). However, analysis of the body composition revealed that body fluid volume significantly decreased only 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 compared with 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 protecting endothelial function but rather from reducing the risk of heart failure.