Insulin Receptor Binding to Monocytes, Insulin Secretion, and Glucose Tolerance Following Metformin Treatment: Results of a Double-Blind Cross-Over Study in Type II Diabetics

We studied the effect of metformin therapy (1700 mg daily) on glucose tolerance, insulin secretion, and insulin binding to monocytes in 10 non-insulin-dependent diabetics (mean duration of disease 2.6 yr) who were treated for 4 wk with either metformin or placebo in a double-blind cross-over study. Metformin induced a significant decrease of glucose levels during an oral glucose load compared with placebo treatment (P less than 0.001). All patients studied showed normal or elevated basal insulin and C-peptide levels; their responses to an oral glucose load, however, were relatively hypoinsulinemic without any significant difference between metformin and placebo. Insulin binding to monocytes was nearly identical at all insulin concentrations tested in the placebo or metformin therapy phase. These data indicate that the glucose-lowering potency of metformin in non-insulin-dependent diabetics cannot be associated with changes in receptor number or affinity. It is suggested that metformin might have a positive influence on postreceptor defects in non-insulin-dependent diabetics.