Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of 2 randomized, clinical trials

Abstract

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut.
 Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260).
 Novelty bullets
 • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle
 • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle
 • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle

Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes

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Recent advances in understanding the mechanisms in skeletal muscle of interaction between exercise and frontline antihyperglycemic drugs

“…Aerobic training increased absolute V O 2 peak by ~10% regardless of placebo or metformin (2000 mg daily) (Pilmark et al., 2021). Follow‐up studies indicated metformin treatment in adults with glucose intolerance did not hinder increases in citrate synthase activity or AMPK activity after acute exercise or 12 weeks of aerobic training (Pilmark et al., 2022). Training did not change mitochondrial respiration in either group, so it is not clear if metformin restricted complex I adaptations.…”

A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: ingenious involvement of gut microbiota and its metabolites

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