Effect of Metformin on Insulin-Stimulated Glucose Turnover and Insulin Binding to Receptors in Type II Diabetes

Euglycemic insulin glucose-clamp and insulin-binding studies on erythrocytes and monocytes were performed in seven type II (non-insulin-dependent) diabetic subjects before and after 4 wk of metformin treatment (850 mg 3 times/day) and in five obese subjects with normal glucose tolerance. Glucose turnover was also measured at basal insulin concentrations and during hyperinsulinemic euglycemic clamps. During euglycemic insulin-glucose clamps, diabetic subjects showed glucose disposal rates of 3.44 ± 0.42 and 7.34 ± 0.34 mg · kg⁻¹ · min⁻¹ (means ± SD) before metformin at insulin infusion rates of 0.80 and 15.37 mU · kg⁻¹ · min⁻¹, respectively. With the same insulin infusion rates, glucose disposal was 4.94 ± 0.55 (P < .01) and 8.99 ± 0.66 (P < .01), respectively, after metformin treatment. Glucose disposal rates in normal obese subjects were 5.76 ± 0.63 (P < .01) and 10.92 ± 1.11 (P < .01) at 0.80 and 15.37 mU · kg⁻¹ · min⁻¹, respectively. Insulin maximum binding to erythrocytes in diabetics was 9.6 ± 4.2 and 5.8 ± 2.6 × 10⁹ cells (means ± SD) before and after metformin treatment, respectively (NS). Insulin maximum binding to monocytes in diabetics was 6.2 ± 2.3 × 10⁷ cells before and 5.0 ± 1.6% after metformin. Hepatic glucose production was higher in the diabetic patients at basal insulin levels, but not at higher insulin concentrations, and was not significantly changed by drug treatment. Basal glucose and insulin concentrations decreased with metformin. Thus, metformin treatment improved glucose disposal rate without significant effect on insulin-binding capacity on circulating cells. Basal hepatic glucose output was slightly lower after metformin treatment in view of lower (9 vs. 15 μU/ml) insulin levels, potentially indicating increased sensitivity of the liver to insulin.