• Carrie G Sharoff, Todd A Hagobian, Steven K Malin, Stuart R Chipkin, Haiyan Yu, Michael F Hirshman, Laurie J Goodyear, and Barry Braun.
• Department of Kinesiology, University of Massachusetts Amherst, USA.
• Am. J. Physiol. Endocrinol. Metab. 2010 Apr 1;298(4):E815-23.

AbstractResults from the Diabetes Prevention Program highlight the effectiveness of metformin or regular physical activity in the prevention of type 2 diabetes. Independently, metformin and exercise increase insulin sensitivity, but they have not been studied in combination. To assess the combined effects, insulin-resistant subjects (n = 9) matched for weight, body fat, and aerobic fitness were studied before any treatment (B), after 2-3 wk of 2,000 mg/day metformin (MET), and after metformin plus 40 min of exercise at 65% Vo(2peak) (MET + Ex). A second group (n = 7) was studied at baseline and after an identical bout of exercise with no metformin (Ex). Biopsies of the vastus lateralis were taken at B, after MET, immediately after MET + Ex (group 1), or immediately after Ex (group 2). Insulin sensitivity was assessed 4 h postexercise with a euglycemic hyperinsulinemic (40 mU.m(2).min(-1)) clamp enriched with [6,6-(2)H]glucose. Insulin sensitivity was 54% higher after Ex (P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPKalpha2 activity was elevated threefold (P < 0.01) after Ex, but there was no increase with MET + Ex. These findings suggest that the combination of short-term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity, and the addition of metformin may attenuate the well-documented effects of exercise alone.

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