The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial

Abstract

IntroductionIn general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity.MethodsHealthy males were eligible for this crossover, counterbalanced study with two treatment periods: MET and placebo (PLA), each lasting 17 days. Treatment dose was gradually increased and reached 2 g/day on treatment day 9, and continued at that level for the rest of the treatment period. The two periods were performed in randomized order. Two experimental days (A+B) were conducted on Day 15 (A) and Day 17 (B) of each period, respectively. Day A consisted of an exercise bout with self-selected exercise intensity (equal to RPE = 14–15 on the Borg Scale). Day B consisted of an exercise bout with fixed intensity (70% of VO2peak). Oxygen consumption rate was assessed continuously during both exercise bouts.ResultsFifteen males (age 23.7 ± 0.6 years, BMI 22.3 ± 2.0, VO2peak 3.5 ± 0.6 L/min) were included in the study. On Day B, RPE was higher in MET compared to PLA (14.8 ± 0.4 vs. 14.0 ± 0.3, P = 0.045). On Day A, no difference in self-selected exercise intensity measured by oxygen consumption rate (PLA 2.33 ± 0.09 L O2/min, MET 2.42 ± 0.10 L O2/min, P = 0.09) was seen between treatment periods.ConclusionsSelf-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.

The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance

“…Despite elevating circulating GDF15, metformin did not influence running distance over 24 hours in WT or in GFRAL KO mice (Figure 1C). This finding contrasts reports suggesting that metformin enhances the perception of exertion during exercise (Das et al, 2018; Kristensen et al, 2019; Pilmark et al, 2021c). We did not observe decreased chow intake in metformin-treated mice (Figure 1D), suggesting that exercise might mask the effects of metformin to lower appetite.…”

The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance

“…Despite elevating circulating GDF15, metformin did not influence running distance over 24 h in WT or in GFRAL KO mice (Figure 1C). This finding contrasts reports suggesting that metformin enhances the perception of exertion during exercise (Das et al, 2018;Kristensen et al, 2019;Pilmark et al, 2021b). We did not observe decreased chow intake in metformin-treated mice (Figure 1D), suggesting that exercise might mask the effects of metformin to lower appetite.…”

The Hormetic Effect of Metformin: “Less Is More”?

“…However, biopsies of skeletal muscle from T2DM patients treated with MTF did not show suppressed Complex I activity [32]. Furthermore, the self-selected exercise intensity was not reduced by MTF in healthy males, even though MTF increased the rate of perceived exertion during an exercise bout with fixed intensity [168]. Moreover, MTF administration seems to activate a mechanism directly related to the hormetic response through the redox state modulation [169].…”