Metformin does not attenuate the acute insulin-sensitizing effect of a single bout of exercise in individuals with insulin resistance

Combining metformin and exercise is recommended for the treatment of insulin resistance. However, it has been suggested that metformin blunts the insulin-sensitizing effects of exercise. We evaluated in a group of insulin-resistant patients the interactions between exercise and their daily dose of metformin. Ten insulin-resistant patients underwent insulin sensitivity assessment using intravenous glucose tolerance test after an overnight fast in the following conditions: (1) after taking their habitual morning dose of metformin (MET), (2) after 45 min of high intensity interval exercise having withheld metformin during 24 h (EX), and (3) after their habitual metformin dose plus an identical exercise bout (MET + EX). During the exercise trials (EX and MET + EX), energy expenditure and substrate oxidation were assessed by indirect calorimetry. In addition, 12-h postprandial blood glucose was measured in all three trials. Insulin sensitivity was similar between MET and EX [4.0 +/- A 0.8 and 4.1 +/- A 0.7 x 10(-4) min(-1) (mu U mL)(-1); P = 0.953] but was 43 % higher than both MET and EX after MET + EX (NS; P = 0.081). Blood glucose disappearance rate was higher after MET + EX than after MET or EX trials (1.7 +/- A 0.2, 1.0 +/- A 0.1, and 1.2 +/- A 0.1 % min(-1), respectively; P = 0.020). There was no difference in postprandial blood glucose concentration after the three meals that followed the trials (P = 0.446). Exercise energy expenditure was 9 % higher during MET + EX than during EX (P = 0.015) partly due to increased carbohydrate oxidation. Our data suggest that habitual metformin treatment in insulin-resistant patients does not blunt the acute insulin-sensitizing effects of a single bout of exercise that on the contrary, tends to enhance it.