Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise

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.

The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet

“…There is inter-individual variability in the metabolic responses to physical training [ 76 ]. Different factors, such as genetic and epigenetic features, nutrition, concomitant treatments, may explain this heterogeneity [ 77 , 78 ]. Gut microbiota composition also may be a potential factor to explain the training response variability [ 79 ].…”

Metabolomic Profile of Skeletal Muscle and Its Change Under a Mixed-Mode Exercise Intervention in Progressively Dysglycemic Subjects

“…All subjects were treated with metformin. Studies have shown that metformin may blunt effects of exercise training on insulin sensitivity improvements and contribute to inter-individual variability for glycemic responses to exercise ( 55 , 56 ). Moreover, metformin abrogates the exercise‐mediated increase in skeletal muscle mitochondrial respiration ( 57 ).…”

AMPK Activity: A Primary Target for Diabetes Prevention with Therapeutic Phytochemicals

“…Interestingly, exercise can increase glucose uptake independent of PI3 kinase activity [10][11][12]. The second pathway involves an insulin-independent signaling system, which is thought to have greater translational relevance for diabetes management [13,14]. When muscles repeat contractions and relaxation during exercise, improvements in insulin sensitivity and glucose tolerance are stimulated [15,16].…”