Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Institute of Mountain Emergency Medicine, EURAC Research, Bolzano, Italy.
Diabetologia. 2021 Feb;64(2):397-409. doi: 10.1007/s00125-020-05282-6. Epub 2020 Sep 26.
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.
Glucose-intolerant (2 h OGTT glucose of 7.8-11.0 mmol/l and/or HbA of 39-47 mmol/mol [5.7-6.5%] or glucose-lowering-medication naive type 2 diabetes), overweight/obese (BMI 25-42 kg/m) 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 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.
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 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).
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 Beckett foundation, A.P Møller Foundation, DDA, the Research Foundation of Rigshospitalet and Trygfonden.
ClinicalTrials.gov (NCT03316690). Graphical abstract.
目的/假设：本平行组、双盲（研究人员和参与者）、随机临床试验的目的是评估二甲双胍和运动训练对葡萄糖耐量受损个体餐后血糖的相互作用。
葡萄糖耐量受损（2 小时 OGTT 血糖 7.8-11.0mmol/l 和/或 HbA 39-47mmol/mol[5.7-6.5%]或葡萄糖降低药物治疗的 2 型糖尿病初发）、超重/肥胖（BMI 25-42kg/m）个体随机分配至安慰剂研究组（PLA，n=15）或二甲双胍研究组（MET，n=14），并进行 3 个实验日：基线（随机分组前）、药物（3 周二甲双胍[2g/天]或安慰剂治疗后）和训练（12 周运动训练联合二甲双胍/安慰剂治疗后）。训练包括监督自行车间歇训练，平均强度为 64%的瓦特，持续 45 分钟，每周 4 次。主要结局是混合餐耐量试验（MMTT）期间的餐后血糖（平均血糖浓度），在每个实验日进行评估。对于组内差异，采用双因素重复测量方差分析评估组×时间交互作用。使用未配对双侧学生 t 检验比较不同时间点的组间变化。
在 PLA 组和 MET 组中，从基线到训练，餐后血糖均有所改善（PLA：-0.7[95%CI-1.4,0.0]mmol/l，p=0.05和 MET：-0.7[-1.5,-0.0]mmol/l，p=0.03），但组间无差异（p=0.92）。在 PLA 中，从药物到训练的整个降低幅度为-0.8[-1.3，-0.1]mmol/l，p=0.01。相反，在 MET 中，从基线到药物的整个降低幅度为-0.9[-1.6，-0.2]mmol/l，p=0.01。从基线到训练的 MMTT 期间的平均血糖浓度降低取决于不同的时间效应：在 PLA 组中，在时间点（t）=120 分钟时观察到下降（p=0.009），而在 MET 组中，在 t=30 分钟时观察到下降（p<0.001）。VO2 增加 15%（4.6[3.3,5.9]mlkgmin，p<0.0001），从药物到训练，体重减轻（-4.0[-5.2，-2.7]kg，p<0.0001），从基线到训练，与组间无差异（p=0.7 和 p=0.5）。
结论/解释：二甲双胍加运动训练在改善餐后血糖方面并不优于单独运动训练。MMTT 期间的差异时间效应提示两种方式之间存在相互作用。
贝克特基金会、A.P 莫勒基金会、DDA、里格医院研究基金会和 Trygfonden。
ClinicalTrials.gov（NCT03316690）。图形摘要。
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