The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial

ABSTRACT

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity.   Ninety individuals with overweight/obesity (BMI>25 m²/kg) and HbA₁c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA₁c-defined prediabetes.

KEYWORDS:

• Metformin
• exercise
• physical activity
• sedentary behaviour
• rate of perceived exertion

Acknowledgments

We are grateful to the study participants for their cooperation and willingness to participate. The laboratory technicians Hanne Vishof, Lars Sander Koch, Sara Sidenius and Camilla Søs Nielsen at SDCC are thanked for their great dedication, skilled assistance and coordination. Hanan Amadid, Kim Clemmensen, Christian S. Hansen, Narges Safai, Nicklas J. Johansen and Johan I. B. Egholk at SDCC, are thanked for their assistance in conducting the study.

Disclosure statement

L.B., K.B.H., F.P., M.E.J. and K.F. are former or current employees by Steno Diabetes Center Copenhagen, a research hospital working in the Danish National Health Service. Until 31 December 2016, Steno Diabetes Center was owned by Novo Nordisk A/S and received part of its core funding from unrestricted grants from the Novo Nordisk Foundation and Novo Nordisk A/S. M.E.J and K.F. own shares in Novo Nordisk A/S. K.F. has received research support from AstraZeneca and Unilever. M.R.-L. has received personal lecture fees from Novo Nordisk A/S. F.P. has received research grants from AstraZeneca, Novo Nordisk, Novartis and lecture fees from MSD, AstraZeneca, Bayer, Novo Nordisk, Novartis, Eli Lilly and Boehringer Ingelheim and has served as a consultant for AstraZeneca, Bayer, Novo Nordisk, Amgen and MSD. M.E.J. has received research grants from Amgen, Sanofi Aventis, Boehringer Ingelheim, Novo Nordisk and AstraZeneca. K.K., L.B., N.S.P., K.B.H. and M.B.B. have nothing to declare.

Author contributions

K.F., F.P. and M.E.J. conceived the idea and designed the PRE-D Trial, while K.K., M.R.-L., N.S.P, K.B.H., M.E.J. and K.F. conceived the idea of the current sub-study. K.F. is sponsor and M.E.J. is principal investigator of the PRE-D study. L.B., M.E.J., M.B.B. and K.F. were involved in the conduct of the trial and data collection. M.R.-L. performed the accelerometer analyses. M.R.-L., M.B.B. and K.K. performed the statistical analyses. K.K. drafted the manuscript. All authors critically interpreted the results, revised the manuscript for important intellectual content, and have read and approved the final version of the manuscript. The corresponding author (K.K.) had full access to all the data and had final responsibility for the decision to submit for publication.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Supplementary material

Supplemental data for this article can be accessed online https://doi.org/10.1080/02640414.2023.2291737

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, and University of Copenhagen.