Improving the Effects of Imeglimin on Endothelial Function: A Prospective, Single-Center, Observational Study

INTRODUCTION: Endothelial dysfunction is a risk factor for cardiovascular disease in patients with diabetes. We hypothesized that imeglimin, a novel oral hypoglycemic agent, would improve endothelial function. METHODS: In this study, imeglimin was administered to patients with type 2 diabetes and HbA1c ≥ 6.5% who were not receiving insulin therapy. A meal tolerance test (592 kcal, glucose 75.0 g, fat 28.5 g) was performed before and 3 months after administration, and endothelial function, blood glucose, insulin, glucagon, and triglycerides were evaluated. Endothelial function was assessed by flow-mediated dilation (FMD). RESULTS: Twelve patients (50% male) with a median age of 55.5 years old (interquartile range [IQR] 51.3-66.0) were enrolled. Fasting FMD did not differ before or 3 months after imeglimin administration (from 6.1 [3.9-8.5] to 6.6 [3.9-9.0], p = 0.092), but 2 h postprandial FMD was significantly improved 3 months after imeglimin administration (from 2.3 [1.9-3.4] to 2.9 [2.4-4.7], p = 0.013). In terms of the glucose profile, imeglimin administration significantly improved HbA1c (from 7.2 ± 0.6% to 6.9 ± 0.6%, p = 0.007), fasting glucose (from 138 ± 19 mg/dL to 128 ± 20 mg/dL, p = 0.020), and 2 h postprandial glucose (from 251 ± 47 mg/dL to 215 ± 68 mg/dL, p = 0.035). The change in 2 h postprandial FMD between before and 3 months after imeglimin administration (Δ2 h postprandial FMD) was negatively correlated with Δ2 h postprandial glucose (r = - 0.653, p = 0.021) in a univariate correlation coefficient analysis. Both patients with and without decreased postprandial glucose 3 months after imeglimin administration had improved postprandial FMD. CONCLUSION: In this small study, imeglimin administration improved 2 h postprandial FMD. Both glycemic control-dependent and -independent mechanisms might contribute to improved endothelial function. TRIAL REGISTRATION: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000046311).