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

BACKGROUND AND AIMS: To assess the interaction between metformin and exercise training on postprandial glucose in individuals with impaired glucose tolerance. MATERIAL AND METHODS: Glucose-intolerant individuals (2-hour oral glucose tolerance test glucose of 7.8-11.0 mmol/l and/or HbA1c of 5.7-6.5% (39-47 mmol/mol) or glucose-lowering-medication naive type 2 diabetes) were randomly allocated to placebo (PLA, n=15) or metformin (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 MET/PLA treatment. Training consisted of supervised bicycle interval sessions at average 64% of Wattmax for 45 minutes, 4 times/week. Postprandial glucose (mean glucose concentration) during a mixed meal tolerance test (MMTT) was assessed on each experimental day. For within-group differences, a group x time interaction was assessed using 2-way repeated measures analysis of variance. Between-group changes of the outcomes at different time points were compared using unpaired two-tailed Students t-tests. RESULTS: Postprandial glucose improved from BASELINE to TRAINING in both PLA and MET (∆PLA: -0.7[-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). 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 concentrations during the MMTT from BASELINE to TRAINING were dependent on differential time effects: In PLA, a decrease was observed at t=120 min (P=0.009), whereas in MET, a reduction occurred at t=30 minutes (P<0.001). VO2peak increased 15% (4.6 [3.3;5.9] ml/kg/min 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). CONCLUSION: 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.