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

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@article{ed77976d2a2f4ddc871ab898c9313e01,
title = "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: 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.",
keywords = "Adaptation, Physiological, Exercise/physiology, Glucose/pharmacology, Humans, Male, Metformin/pharmacology, Muscle, Skeletal/physiology",
author = "Pilmark, {Nanna Skytt} and Laura Oberholzer and Halling, {Jens Frey} and Kristensen, {Jonas M} and B{\o}nding, {Christina Pedersen} and Ida Elkj{\ae}r and Mark Lyngb{\ae}k and Grit Elster and Christoph Siebenmann and Holm, {Niels Frederich} and Birk, {Jesper Bratz Bratz} and Larsen, {Emil List} and Anne-Kristine Meinild-Lundby and Wojtaszewski, {J F} and Henriette Pilegaard and Henrik Poulsen and Pedersen, {Bente Klarlund} and Hansen, {Katrine Bagge} and Kristian Karstoft",
year = "2022",
month = mar,
doi = "10.1139/apnm-2021-0194",
language = "English",
volume = "47",
pages = "309--320",
journal = "Applied Physiology, Nutrition and Metabolism",
issn = "1715-5312",
publisher = "N R C Research Press",
number = "3",

}

RIS

TY - JOUR

T1 - Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans

T2 - secondary analyses of 2 randomized, clinical trials

AU - Pilmark, Nanna Skytt

AU - Oberholzer, Laura

AU - Halling, Jens Frey

AU - Kristensen, Jonas M

AU - Bønding, Christina Pedersen

AU - Elkjær, Ida

AU - Lyngbæk, Mark

AU - Elster, Grit

AU - Siebenmann, Christoph

AU - Holm, Niels Frederich

AU - Birk, Jesper Bratz Bratz

AU - Larsen, Emil List

AU - Meinild-Lundby, Anne-Kristine

AU - Wojtaszewski, J F

AU - Pilegaard, Henriette

AU - Poulsen, Henrik

AU - Pedersen, Bente Klarlund

AU - Hansen, Katrine Bagge

AU - Karstoft, Kristian

PY - 2022/3

Y1 - 2022/3

N2 - 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: 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.

AB - 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: 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.

KW - Adaptation, Physiological

KW - Exercise/physiology

KW - Glucose/pharmacology

KW - Humans

KW - Male

KW - Metformin/pharmacology

KW - Muscle, Skeletal/physiology

UR - http://www.scopus.com/inward/record.url?scp=85125882448&partnerID=8YFLogxK

U2 - 10.1139/apnm-2021-0194

DO - 10.1139/apnm-2021-0194

M3 - Journal article

C2 - 34784247

VL - 47

SP - 309

EP - 320

JO - Applied Physiology, Nutrition and Metabolism

JF - Applied Physiology, Nutrition and Metabolism

SN - 1715-5312

IS - 3

ER -

ID: 69626318