PMID- 32979074 OWN - NLM STAT- MEDLINE DCOM- 20220120 LR - 20221207 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 64 IP - 2 DP - 2021 Feb TI - The interaction between metformin and physical activity on postprandial glucose and glucose kinetics: a randomised, clinical trial. PG - 397-409 LID - 10.1007/s00125-020-05282-6 [doi] 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's t tests. RESULTS: Postprandial 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). 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. FUNDING: The Beckett foundation, A.P Moller Foundation, DDA, the Research Foundation of Rigshospitalet and Trygfonden. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03316690). Graphical abstract. FAU - Pilmark, Nanna S AU - Pilmark NS AUID- ORCID: 0000-0001-9963-8802 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Lyngbaek, Mark AU - Lyngbaek M AUID- ORCID: 0000-0002-1931-9658 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Oberholzer, Laura AU - Oberholzer L AUID- ORCID: 0000-0003-4372-0051 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Elkjaer, Ida AU - Elkjaer I AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Petersen-Bonding, Christina AU - Petersen-Bonding C AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Kofoed, Katja AU - Kofoed K AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Siebenmann, Christoph AU - Siebenmann C AUID- ORCID: 0000-0002-0315-3761 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. AD - Institute of Mountain Emergency Medicine, EURAC Research, Bolzano, Italy. FAU - Kellenberger, Katja AU - Kellenberger K AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. AD - Section for Elite Sport, Swiss Federal Institute of Sports, Magglingen, Switzerland. FAU - van Hall, Gerrit AU - van Hall G AUID- ORCID: 0000-0002-2519-8127 AD - Biomedical Sciences, Faculty of Health & Medical Science, University of Copenhagen, Copenhagen, Denmark. AD - Clinical Metabolomics Core Facility, Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. FAU - Abildgaard, Julie AU - Abildgaard J AUID- ORCID: 0000-0003-1317-7051 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. AD - Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. FAU - Ellingsgaard, Helga AU - Ellingsgaard H AUID- ORCID: 0000-0002-9105-5247 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Lauridsen, Carsten AU - Lauridsen C AUID- ORCID: 0000-0003-3383-4688 AD - Department of Diagnostic Radiology, Copenhagen University Hospital, Copenhagen, Denmark. AD - Copenhagen University College, Copenhagen N, Denmark. FAU - Ried-Larsen, Mathias AU - Ried-Larsen M AUID- ORCID: 0000-0002-8388-5291 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Pedersen, Bente K AU - Pedersen BK AUID- ORCID: 0000-0001-6508-6288 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Hansen, Katrine B AU - Hansen KB AUID- ORCID: 0000-0002-2587-5589 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - Karstoft, Kristian AU - Karstoft K AUID- ORCID: 0000-0002-6596-4199 AD - Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Kristian.karstoft@regionh.dk. AD - Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Kristian.karstoft@regionh.dk. LA - eng SI - ClinicalTrials.gov/NCT03316690 GR - ID 101390 and ID 20045/The Center of Inflammation and Metabolism/Center for Physical Activity Research is supported by a grant from Trygfonden/ GR - E-23606-03/Rigshospitalet Research Foundation/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200926 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 9100L32L2N (Metformin) SB - IM MH - Adult MH - Blood Glucose/*metabolism MH - Combined Modality Therapy MH - Diabetes Mellitus, Type 2/metabolism/*therapy MH - Double-Blind Method MH - Exercise/*physiology MH - Female MH - Glucose Intolerance/metabolism/*therapy MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Metformin/*therapeutic use MH - Middle Aged MH - *Postprandial Period MH - Prediabetic State/metabolism/*therapy OTO - NOTNLM OT - Exercise OT - Impaired glucose tolerance OT - Interaction OT - Metformin OT - Mixed meal tolerance test OT - Postprandial glucose OT - Prediabetes OT - Stable isotope glucose tracers OT - Training EDAT- 2020/09/27 06:00 MHDA- 2022/01/21 06:00 CRDT- 2020/09/26 12:04 PHST- 2020/04/23 00:00 [received] PHST- 2020/08/10 00:00 [accepted] PHST- 2020/09/27 06:00 [pubmed] PHST- 2022/01/21 06:00 [medline] PHST- 2020/09/26 12:04 [entrez] AID - 10.1007/s00125-020-05282-6 [pii] AID - 10.1007/s00125-020-05282-6 [doi] PST - ppublish SO - Diabetologia. 2021 Feb;64(2):397-409. doi: 10.1007/s00125-020-05282-6. Epub 2020 Sep 26.