The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial

Abstract

Aims/hypothesis The aim of this parallel-group, double-blinded (study personnel and participants), randomised clinical trial was to assess the interaction between metformin and exercise training on postprandial glucose in glucose-intolerant individuals. Methods Glucose-intolerant (2 h OGTT glucose of 7.8-11.0 mmol/l and/or HbA 1c of 39-47 mmol/mol [5.7-6.5%] or glucoselowering-medication naive type 2 diabetes), overweight/obese (BMI 25-42 kg/m 2 ) individuals were randomly allocated to a placebo study group (PLA, n = 15) or a metformin study group (MET, n = 14), and underwent 3 experimental days: BASELINE (before randomisation), MEDICATION (after 3 weeks of metformin [2 g/day] or placebo treatment) and TRAINING (after 12 weeks of exercise training in combination with metformin/placebo treatment). Training consisted of supervised bicycle interval sessions with a mean intensity of 64% of Watt max for 45 min, 4 times/week. The primary outcome was postprandial glucose (mean glucose concentration) during a mixed meal tolerance test (MMTT), which was assessed on each experimental day. For within-group differences, a group × time interaction was assessed using two-way repeated measures ANOVA. Between-group changes of the outcomes at different timepoints were compared using unpaired two-tailed Student's t tests.Results Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group (ΔPLA: −0.7 [95% CI −1.4, 0.0] mmol/l, p = 0.05 and ΔMET: −0.7 [−1.5, −0.0] mmol/l, p = 0.03), with no between-group difference (p = 0.92). In PLA, the entire reduction was seen from MEDICATION to TRAINING (−0.8 [−1.3, −0.1] mmol/l, p = 0.01). Conversely, in MET, the entire reduction was observed from BASELINE to MEDICATION (−0.9 [−1.6, −0.2] mmol/l, p = 0.01). The reductions in mean glucose concentration during the MMTT from BASELINE to TRAINING were dependent on differential time effects: in the PLA group, a decrease was observed at timepoint (t) = 120 min (p = 0.009), whereas in the MET group, a reduction occurred at t = 30 min (p < 0.001). V̇O 2peak increased 15% (4.6 [3.3, 5.9] ml kg −1 min −1 , p < 0.0001) from MEDICATION to TRAINING and body weight decreased (−4.0 [−5.2, −2.7] kg, p < 0.0001) from BASELINE to TRAINING, with no between-group differences (p = 0.7 and p = 0.5, respectively). Conclusions/interpretation Metformin plus exercise training was not superior to exercise training alone in improving postprandial glucose. The differential time effects during the MMTT suggest an interaction between the two modalities.

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

“…The screening day included a medical examination, recording of medical history, a blood chemistry screen, an ECG and a cardiorespiratory fitness (VO 2 peak) test on a cycle ergometer (Monark 739E, Varberg, Sweden) using indirect calorimetry (Cosmed Quark, Rome, Italy). The VO 2 peak test started with a 5-min warm up at 80 Watt (W), after which the load was gradually increased by 20 W every minute until at least one of the following criteria was met: plateau of HR and VO 2 with incremental workloads, respiratory exchange ratio > 1.1, or volitional exhaustion, as previously described (12). Written informed consent was obtained from all participants.…”

Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus

“…52,53,71 Similarly, as previously described, metformin shares AMPK as a common target for glucose regulation, but the combination of these two modalities seems to be unclear and potentially conflicting (Table 1). [14][15][16][17][18][19][20][21][22][23][24][25][26][27] in which participants continued their habitual dose; ↔, there was no difference between combined treatments and exercise alone;…”

“…However, although this notion seems plausible, research on this topic is still unclear, with inconclusive and mixed results. [14][15][16][17][18][19][20][21][22][23][24][25][26][27]…”

“…While exercise and metformin are the most prescribed modalities to manage T2DM due to the similar effects on glucose control; in recent years some studies showed the potential negation of the positive effects that these modalities can have if implemented together. [14][15][16][17][18][19][20][21][22][23][24][25][26][27] Because the research in this area is scarce and results are inconsistent, a comprehensive review of the studies is needed to further elucidate the impact of the combination of exercise and metformin on the management of metabolic pathophysiology of T2DM. Additionally, discussion about the effects of exercise and metformin cannot only focus on the management of T2DM but must be extended further to describe the interactions of two modalities.…”

Association between metformin and physical activity with glucose control in adults with type 2 diabetes

“…The combined association between metformin and regular physical activity on glycaemic control in type 2 diabetes has been studied in a few smaller studies 11–15 and some suggest that there may be acute effects of exercise on glucose, 11,13 but it is unclear whether these differences translate into meaningful chronic differences in glucose or glucose control. Some of these studies suggest that beneficial effects of exercise on glucose metabolism and insulin sensitivity may be attenuated in those taking metformin 11,13,15,16 . Thus, the objective of the current study is to examine the combined association between metformin and regular physical activity on glycaemic control in adults with type 2 diabetes.…”