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Pilmark NS, Oberholzer L, Halling JF, et al. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials. Appl Physiol Nutr Metab. 2021;doi: 10.1139/apnm-2021-0194.
Pilmark, N. S., Oberholzer, L., Halling, J. F., Kristensen, J. M., Bønding, C. P., Elkjær, I., Lyngbæk, M., Elster, G., Siebenmann, C., Holm, N. F., Birk, J. B. B., Larsen, E. L., Meinild-Lundby, A. K., Wojtaszewski, J. F., Pilegaard, H., Poulsen, H., Pedersen, B. K., Hansen, K. B., & Karstoft, K. (2021). Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, . https://doi.org/10.1139/apnm-2021-0194
Pilmark, Nanna Skytt, et al. "Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials." Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme vol. (2021). doi: https://doi.org/10.1139/apnm-2021-0194
Pilmark NS, Oberholzer L, Halling JF, Kristensen JM, Bønding CP, Elkjær I, Lyngbæk M, Elster G, Siebenmann C, Holm NF, Birk JBB, Larsen EL, Meinild-Lundby AK, Wojtaszewski JF, Pilegaard H, Poulsen H, Pedersen BK, Hansen KB, Karstoft K. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials. Appl Physiol Nutr Metab. 2021 Nov 16; doi: 10.1139/apnm-2021-0194. Epub 2021 Nov 16. PMID: 34784247.
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Appl Physiol Nutr Metab. 2021 Nov 16; doi: 10.1139/apnm-2021-0194. Epub 2021 Nov 16.

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

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme

Nanna Skytt Pilmark, Laura Oberholzer, Jens Frey Halling, Jonas M Kristensen, Christina Pedersen Bønding, Ida Elkjær, Mark Lyngbæk, Grit Elster, Christoph Siebenmann, Niels Frederich Holm, Jesper Bratz Bratz Birk, Emil List Larsen, Anne-Kristine Meinild-Lundby, J F Wojtaszewski, Henriette Pilegaard, Henrik Poulsen, Bente Klarlund Pedersen, Katrine Bagge Hansen, Kristian Karstoft

Affiliations

  1. Rigshospitalet, 53146, Centre for Physical Activity Research (CFAS), Copenhagen, Denmark; [email protected].
  2. Center for Physical Activity Research, University Hospital of Copenhagen, Blegdamsvej 9, Copenhagen, Denmark, 2100; [email protected].
  3. university of copenhagen, department of biology, , copenhagen, Denmark; [email protected].
  4. University of Copenhagen, Denmark, Department of Nutrition, Exercise and Sports,, copenhagen, Denmark; [email protected].
  5. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  6. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  7. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  8. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  9. Institute of Mountain Emergency Medicine,, EURAC Research, Bolzano, Italy, bolzano, Italy; [email protected].
  10. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  11. University of Copenhagen, Denmark, Department of Nutrition, Exercise and Sports,, copenhagen, Denmark; [email protected].
  12. Copenhagen University Hospital, 53146, Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Kobenhavn, Denmark; [email protected].
  13. Center for Physical Activity Research, University Hospital of Copenhagen, Copenhagen, Denmark; [email protected].
  14. University of Copenhagen, Denmark, Department of Nutrition, Exercise and Sports,, copenhagen, Denmark; [email protected].
  15. university of copenhagen, department of biology, , copenhagen, Denmark; [email protected].
  16. Copenhagen University Hospital, 53146, Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Kobenhavn, Denmark; [email protected].
  17. Rigshospitalet, 53146, Centre of Inflammation and Metabolism / Centre for Physical Activity Research (CIM/CFAS), København, Denmark; [email protected].
  18. Steno Diabetes Center Copenhagen, 53138, Steno Diabetes Center Copenhagen, Gentofte, Denmark, Gentofte, Denmark; [email protected].
  19. Rigshospitalet, 53146, Centre for Physical Activity Research (CFAS), Blegdamsvej 9, Copenhagen, Denmark, 2100.
  20. Bispebjerg Hospital, 53166, Department of Clinical Pharmacology, Copenhagen, Denmark, 2400; [email protected].

PMID: 34784247 DOI: 10.1139/apnm-2021-0194

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.

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