To test whether metformin treatment might improve peripheral insulin sensitivity in non insulin dependent diabetes, we measured peripheral glucose uptake in 12 non insulin dependent diabetics before (A) and after 4 weeks (B) of metformin therapy (2 .times. 850 mg/day) by the hyperinsulinemic clamp technique (80 mU/m2/min). In addition, insulin binding monocytes was compared between A and B. Diabetic control, evaluated by measurement of fasting blood glucose and glycosylated hemoglobin, was significantly improved by metformin treatment (P < 0.01). Insulin binding to monocytes was not significantly influenced by metformin (A-4,53 % vs. B-5,12 %, n.s. at insulin tracer concentration). Peripheral glucose utilisation improved slightly, but significantly after 4 weeks of metformin therapy (A: 4,4 .+-. 0,6 mg/kg/min, B: 5,4 .+-. 0.8 mg/kg/min, p < 0.01). Improvement in peripheral glucose utilisation correlated significantly with improved metabolic control, estimated by fasting blood glucose measurements (p < 0.01).