The Interaction Between Metformin and Physical Training

Summary

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 5' adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle and liver, and the activation of AMPK results in many different metabolic effects, including improvements in glycemic control. Because of this similarity in mechanism of action, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. Thus, the aim of this study is to assess the effects of training with and without concomitant metformin treatment, in order to investigate whether an interaction between the two occur. Subjects with impaired glucose tolerance will all undergo 12 weeks of training but will be randomized (1:1) to concomitant metformin/placebo treatment in a double-blinded way. Experimental days will be performed before randomisation (before initiation of metformin/placebo treatment), before initiation of the training period and after the training period.

Timeline

Start

2017-10-20

Primary completion

2018-10-01

Completion

2018-10-01

Outcome

Missed primary endpoint

paper Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group (∆PLA: -0.7 [95% CI -1.4, 0.0] mmol/l, p = 0.05 and ∆MET: -0.7 [-1.5, -0.0] mmol/l, p = 0.03), with no between-group difference (p = 0.92). PMID 32979074 ↗

paper Metformin plus exercise training was not superior to exercise training alone in improving postprandial glucose. PMID 32979074 ↗

Publications

• 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.
• Pilmark NS, Lyngbaek M, Oberholzer L, Elkjaer I, Petersen-Bonding C, Kofoed K, Siebenmann C, Kellenberger K, van Hall G, Abildgaard J, Ellingsgaard H, Lauridsen C, Ried-Larsen M, Pedersen BK, Hansen KB, Karstoft K. The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial. Diabetologia. 2021 Feb;64(2):397-409. doi: 10.1007/s00125-020-05282-6. Epub 2020 Sep 26.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Metformin	Small molecule	1000 mg	—

Indications