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

Abstract

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 C 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 (D2 h postprandial FMD) was negatively correlated with D2 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 andindependent mechanisms might contribute to improved endothelial function.Trial Registration: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000046311).

Actual Meal of Low Carbohydrate Diet (LCD) for Diabetic Patient Treated by Effective Imeglimin (Twymeeg)

“…Based on this data, the add-on treatment of Twymeeg appears to be beneficial for achieving a satisfactory level of clinical practice [21]. Imeglimin may have crucial functions involving the mitochondrial mechanism for glucose and related processes [22]. Consequently, future research is expected to clarify several metabolic pathways related to imeglimin.…”

Novel Therapeutics for Type 2 Diabetes Mellitus—A Look at the Past Decade and a Glimpse into the Future

“…The underlying mechanisms can be attributable to improved nitric oxide synthesis, reduced oxidative stress specifically produced by reverse electron transport in the mitochondria, and the minimized hyperglycemia-induced apoptosis of endothelial cells [195]. An improvement in endothelial function due to imeglimin has been demonstrated by an improvement in postprandial FMD in humans [196]. Regarding cardiac function, dysfunctional unfolded protein response has been postulated to lead to heart failure with a preserved ejection fraction.…”

Letter to the Editor: Can Imeglimin Improve the Systolic Time Intervals in Diabetes Mellitus?

“…We read with great interest the article by Uchida et al regarding the effect of imeglimin on endothelial function [ 1 ]. The authors have demonstrated for the first time that 3 months of imeglimin treatment in patients with type 2 diabetes mellitus improved flow-mediated vasodilation.…”