The Effect of Intravenous Metformin on Glucose Metabolism During Hyperglycaemia in Type 2 Diabetes

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Abstract
A stepped intravenous metformin infusion was used in conjunction with the hyperglycaemic clamp technique to study the dose‐response relationship of plasma metformin concentration with hepatic glucose production and peripheral glucose disposal in nine patients with Type 2 diabetes. The study was of double‐blind crossover design, using NaCl infusion as control. Plasma metformin concentrations spanning the therapeutic range (1.64 ± 0.13 mg I−1 and 6.57 ± 0.61 mg I−1) were achieved. No differences in peripheral glucose disposal were demonstrated when compared with NaCl infusion (3.4 ± 0.1 vs 3.6 ± 0.2 (±SE) mg kg−1 min−1 and 3.4 ± 0.2 vs 3.3 ± 0.2 mg kg−1 min−1, respectively). There was also no difference in basal hepatic glucose production during metformin and NaCl infusion (2.7 ± 0.3 vs 2.8 ± 0.2 mg kg−1 min−1). No acute effect of metformin on hepatic glucose production or peripheral glucose disposal was observed, implying that a chronic persistent effect is more important in these respects than immediate effects consequent upon changes in plasma drug level.