Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals

Sharoff CG, Hagobian TA, Malin SK, Chipkin SR, Yu H, Hirshman MF, Goodyear LJ, Braun B. Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals. Am J Physiol Endocrinol Metab 298: E815-E823, 2010. First published January 13, 2010; doi:10.1152/ajpendo.00517.2009.-Results 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-H-2] glucose. Insulin sensitivity was 54% higher after Ex (P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPK alpha 2 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.