The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation

The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation

The Effects of Metformin on Self-selected Exercise Intensity, Physical Fitness and Exercise-induced AMPK-activation

The purpose of this study is to evaluate the potential interaction between metformin and exercise in order to optimize clinical guidelines for treatment of T2D.

Physical activity is a first line treatment for patients with type 2 diabetes (T2D ), however, the vast majority of patients with T2D do not achieve satisfying glycemic control with physical activity alone, which is why pharmacological treatment with metformin is most often initiated. It is known that metformin and exercise both activates AMPK, which results in many different metabolic effects. Because of this similarity, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. With this study the investigators aim to look at the individual and combined effects of metformin and exercise in order to investigate whether an interaction occur. An Interaction will have tremendous clinical importance for patients with T2D given current guidelines where the vast majority of these patients are recommended both exercise and metformin treatment. The investigators hypothesize that metformin treatment reduces self-selected exercise intensity, which may be explained via decreased mitochondrial complex 1 function, increased blood lactate levels, heart rate and RPE during exercise. Furthermore exercise-induced AMPK-activation is reduced with metformin treatment.

Mean rate of perceived exertion (Borg scale) during a 45 min ergometer cycling bout with fixed intensity

change in exercise induced AMPK-activation after compared to before a 45 min ergometer cycling bout with self-selected intensity

Mitochondrial Complex I respiration in skeletal muscle tissue after 17 days of metformin/placebo treatment

Inclusion Criteria: male HbA1c < 39 mmol/l BMI < 25 structured physical activity < = 150 min/week apparently healthy Exclusion Criteria: smoking daily pharmaceutical treatment contraindication to increased levels of physical activity ALAT/ASAT elevated 3 times above upper normal values renal insufficiency (eGFR < 60 ml/min) prior history of lactic acidosis

Pilmark NS, Oberholzer L, Halling JF, Kristensen JM, Bonding CP, Elkjaer I, Lyngbaek M, Elster G, Siebenmann C, Holm NFR, Birk JB, Larsen EL, Lundby AM, Wojtaszewski J, Pilegaard H, Poulsen HE, Pedersen BK, Hansen KB, Karstoft K. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of 2 randomized, clinical trials. Appl Physiol Nutr Metab. 2022 Mar;47(3):309-320. doi: 10.1139/apnm-2021-0194. Epub 2021 Nov 16.