Metformin and Vascular Function in Prediabetes

Prediabetes affects approximately 98 million people in the United States and significantly elevates the risk of cardiovascular disease (CVD) and progression to type-2 diabetes. Endothelial dysfunction, characterized by reduced nitric oxide bioavailability, is a key subclinical risk factor contributing to the increased CVD risk in prediabetes. Additionally, endothelial dysfunction exacerbates insulin resistance and hyperglycemia, further elevating the likelihood of progression to overt diabetes. Thus, targeting endothelial dysfunction in prediabetes presents a strategic opportunity to mitigate the risks of both CVD and overt diabetes.

Hyperglycemia-induced reactive oxygen species (ROS) generation reduces nitric oxide bioavailability, driving endothelial dysfunction in prediabetes. Therefore, interventions that lower hyperglycemia could decrease ROS production, enhance nitric oxide bioavailability, and improve endothelial function in prediabetes. Metformin, a first-line anti-diabetic agent, lowers hyperglycemia by reducing hepatic glucose output and enhancing insulin-mediated glucose uptake. Despite its established vascular benefits in diabetes, the effects of metformin on endothelial function in prediabetes remain unexplored.

This study will enroll 30 individuals in a randomized, double-blind, placebo-controlled clinical trial utilizing innovative methodologies to elucidate the vascular benefits of metformin in prediabetes. Specifically, the investigators will assess 1) large conduit artery endothelial function, and 2) cutaneous microvascular endothelial function in prediabetes. By investigating these mechanisms, the investigators aim to provide critical insights into metformin's potential to reduce CVD risk and prevent the progression to diabetes in individuals with prediabetes.