Journal Article

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

Abildgaard, Julie, Karstoft Kristian, Lyngbæk, Mark, Lauridsen Carsten, Ried-Larsen, Mathias, Petersen-Bønding, Christina, Kofoed Katja, Pilmark, Nanna S, Kellenberger Katja, Elkjær Ida, van Hall Gerrit, Oberholzer, Laura, Pedersen, Bente K, Siebenmann Christoph, Ellingsgaard Helga, Hansen, Katrine B

2021

Overview

Aims/hypothesisThe 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.MethodsGlucose-intolerant (2 h OGTT glucose of 7.8–11.0 mmol/l and/or HbA1c of 39–47 mmol/mol [5.7–6.5%] or glucose-lowering-medication naive type 2 diabetes), overweight/obese (BMI 25–42 kg/m2) 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 Wattmax 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.ResultsPostprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group (∆PLA: −0.7 [95% CI −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 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). V̇O2peak 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/interpretationMetformin 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.FundingThe Beckett foundation, A.P Møller Foundation, DDA, the Research Foundation of Rigshospitalet and Trygfonden.Trial registrationClinicalTrials.gov (NCT03316690).

• Publisher: Springer Nature B.V
• Subject: Antidiabetics / Body weight / Clinical trials / Diabetes mellitus (non-insulin dependent) / Exercise / Fitness training programs / Glucose / Metformin / Overweight / Physical activity / Physical fitness / Physical training / Placebos