TY - JOUR

T1 - The interaction between metformin and physical activity on postprandial glucose and glucose kinetics

T2 - a randomised, clinical trial

AU - Pilmark, Nanna S.

AU - Lyngbæk, Mark

AU - Oberholzer, Laura

AU - Elkjær, Ida

AU - Petersen-Bønding, Christina

AU - Kofoed, Katja

AU - Siebenmann, Christoph

AU - Kellenberger, Katja

AU - van Hall, Gerrit

AU - Abildgaard, Julie

AU - Ellingsgaard, Helga

AU - Lauridsen, Carsten

AU - Ried-Larsen, Mathias

AU - Pedersen, Bente K.

AU - Hansen, Katrine B.

AU - Karstoft, Kristian

PY - 2021

Y1 - 2021

N2 - 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 glucose-lowering-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 x 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'sttests.Results Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group ( increment PLA: -0.7 [95% CI -1.4, 0.0] mmol/l,p = 0.05 and increment 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 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). (V) over dotO(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 andp = 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.

AB - 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 glucose-lowering-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 x 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'sttests.Results Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group ( increment PLA: -0.7 [95% CI -1.4, 0.0] mmol/l,p = 0.05 and increment 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 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). (V) over dotO(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 andp = 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.

KW - Exercise

KW - Impaired glucose tolerance

KW - Interaction

KW - Metformin

KW - Mixed meal tolerance test

KW - Postprandial glucose

KW - Prediabetes

KW - Stable isotope glucose tracers

KW - Training

KW - TYPE-2 DIABETES-MELLITUS

KW - GLYCEMIC CONTROL

KW - INSULIN SENSITIVITY

KW - EXERCISE

KW - INDIVIDUALS

KW - PEOPLE

KW - MASS

KW - AMPK

U2 - 10.1007/s00125-020-05282-6

DO - 10.1007/s00125-020-05282-6

M3 - Journal article

C2 - 32979074

VL - 64

SP - 397

EP - 409

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

ER -