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The Effect of Metformin on Glucose Homeostasis During Moderate Exercise

OBJECTIVE We investigated the role of metformin on glucose kinetics during moderate exercise. RESEARCH DESIGN AND METHODS Before, during, and after a 45-min bout of exercise at 60% VO2max, glucose kinetics were determined by isotope tracer technique in patients with type 2 diabetes mellitus with metformin treatment (DM2+Met) or without metformin treatment (DM2) and in healthy control subjects (CON) matched for BMI and age. Glucoregulatory hormones and metabolites were measured throughout the study. RESULTS Plasma glucose concentration was unchanged during exercise in CON but decreased in DM2. No significant change was found in DM2+Met. Hormones and metabolites showed no differences among the groups except for elevated exercise-induced concentrations of lactate in DM2 (area under the curve [AUC] 31 ± 1% vs. CON) and glucagon in DM2 (AUC 5 ± 1% vs. DM2+Met). Free fatty acid levels were lower in DM2+Met than in DM2 (AUC −14 ± 1%). Absolute values of the baseline glucose rate of appearance (Ra) were elevated in DM2 and DM2+Met, but the increase in glucose Ra relative to baseline was blunted in DM2 (19 ± 1%) and DM2+Met (18 ± 4%) compared with CON (46 ± 4%). Glucose rate of disappearance relative to baseline increased more in CON (31 ± 3%) than in DM2 (6 ± 1%) and DM2+Met (21 ± 2%), showing a small increase caused by metformin. Glucose metabolic clearance rate relative to baseline was similar during exercise in DM2 (33 ± 1%) and CON (35 ± 3%) but was improved in DM2+Met (37 ± 3%) compared with DM2. CONCLUSIONS Metformin has a positive effect on glucose homeostasis during exercise.