Metformin and/or exercise training affect metabolic health in men and women with prediabetes

Prediabetes is defined by elevated blood glucose concentrations not high enough to meet criteria for type 2 diabetes. Exercise or metformin, a common anti-diabetes medication, may attenuate the progression from prediabetes to type 2 diabetes by improving insulin sensitivity and cardio-metabolic health. Because each treatment has its primary action in different tissues, combining exercise (muscle) with metformin (liver) may further enhance insulin sensitivity and cardio-metabolic health. Purpose. To determine the efficacy of combining exercise training with metformin on insulin sensitivity and cardio-metabolic health in men and women with prediabetes. We hypothesized that the combined treatment would improve insulin sensitivity and cardio-metabolic health more than either treatment alone. Methods. Thirty-two men and women with prediabetes were placed in placebo (P), metformin (M), exercise training and placebo (EP), or exercise training and metformin (EM) groups. Pill distribution was double-blind, and the groups were well-matched for age, weight, and fitness. There were no baseline differences in any characteristic. Subjects were provided P or 2000mg/d of M for 12 weeks and EM and EP underwent a progressive training protocol. Insulin sensitivity was measured 28–30hr post-exercise with a euglycemic hyperinsulinemic clamp. Traditional cardio-metabolic measures were also collected in the fasted state (e.g. blood pressure, blood lipids and inflammation). Group means were compared using a 2-way repeated measures analysis of variance. Results. Relative to baseline, all 3 interventions increased insulin sensitivity (p \u3c 0.05), however, EP increased insulin sensitivity approximately 25–30% more than either EM or M. Compared to control, EP and M both lowered systolic blood pressure and C-reactive protein (p \u3c 0.05, p = 0.06) and these reductions were approximately 15% more than EM. Each treatment raised HDL (p \u3c 0.05). Enhanced insulin sensitivity was associated with increased non-oxidative glucose metabolism (i.e. glucose storage) (r = 0.85; p \u3c 0.01). Conclusions. Despite more weight loss (4 kg), metformin blunted, rather than accentuated the effects of training on enhancing insulin sensitivity and lowering systolic blood pressure and inflammation. Given that metformin and physical activity are widely recommended treatments for prediabetes, it is important to better understand the mechanisms and ramifications of the combined treatment