Aim To investigate whether an intensive lifestyle intervention induces partial or complete type 2 diabetes (T2D) remission. Materials and methods In a secondary analysis of a randomized, assessor‐blinded, single‐centre trial, people with non‐insulin‐dependent T2D (duration <10 years), were randomly assigned (2:1, stratified by sex, from April 2015 to August 2016) to a lifestyle intervention group (n = 64) or a standard care group (n = 34). The primary outcome was partial or complete T2D remission, defined as non‐diabetic glycaemia with no glucose‐lowering medication at the outcome assessments at both 12 and 24 months from baseline. All participants received standard care, with standardized, blinded, target‐driven medical therapy during the initial 12 months. The lifestyle intervention included 5‐ to 6‐weekly aerobic and combined aerobic and strength training sessions (30‐60 minutes) and individual dietary plans aiming for body mass index ≤25 kg/m2. No intervention was provided during the 12‐month follow‐up period. Results Of the 98 randomized participants, 93 completed follow‐up (mean [SD] age 54.6 [8.9] years; 46 women [43%], mean [SD] baseline glycated haemoglobin 49.3 [9.3] mmol/mol). At follow‐up, 23% of participants (n = 14) in the intervention and 7% (n = 2) in the standard care group met the criteria for any T2D remission (odds ratio [OR] 4.4, 95% confidence interval [CI] 0.8‐21.4]; P = 0.08). Assuming participants lost to follow‐up (n = 5) had relapsed, the OR for T2D remission was 4.4 (95% CI 1.0–19.8; P = 0.048). Conclusions The statistically nonsignificant threefold increased remission rate of T2D in the lifestyle intervention group calls for further large‐scale studies to understand how to implement sustainable lifestyle interventions among people with T2D.

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 glucoselowering-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 × 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 (ΔPLA: −0.7 [95% CI −1.4, 0.0] mmol/l, p = 0.05 and ΔMET: −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.

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