Abstract

Metformin and exercise independently improve glycemic control. Metformin traditionally is considered to reduce hepatic glucose production, while exercise training is thought to stimulate skeletal muscle glucose disposal. Collectively, combining treatments would lead to the anticipation for additive glucose regulatory effects. Herein, we discuss recent literature suggesting that metformin may inhibit, enhance or have no effect on exercise mediated benefits toward glucose regulation, with particular emphasis on insulin sensitivity. Importantly, we address issues surrounding the impact of metformin on exercise induced glycemic benefit across multiple insulin sensitive tissues (e.g., skeletal muscle, liver, adipose, vasculature, and the brain) in effort to illuminate potential sources of inter-individual glycemic variation. Therefore, the review identifies gaps in knowledge that require attention in order to optimize medical approaches that improve care of people with elevated blood glucose levels and are at risk of cardiovascular disease.

Highlights

  • 34.2 million individuals in the U.S have type 2 diabetes, and ∼88 million men and women have prediabetes [1]

  • The collective literature suggests that, if anything, metformin attenuates the effects of exercise at improving insulin sensitivity at the level of skeletal muscle

  • Systemic studies determining the benefit of different exercise doses as well as risk factors of people co-prescribed metformin would enable individualized treatments that favor glycemic control

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Summary

Introduction

34.2 million individuals in the U.S have type 2 diabetes, and ∼88 million men and women have prediabetes [1]. We have shown that changes in circulating FFAs following moderate intensity training are directly related to improved peripheral insulin sensitivity [32] and short-term interval or continuous exercise increases adipose insulin sensitivity in adults with prediabetes [19].

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