Metformin treatment leads to an increase in basal, but not insulin-stimulated, glucose disposal in obese patients with impaired glucose tolerance

Aims This study was initiated to test the hypothesis that metformin treatme nt leads to enhanced glucose disposal at ambient insulin concentrations. Methods Nineteen obese patients with impaired glucose tolerance (IGT) were treated with either metformin or placebo in a randomized, double-blind, pla cebo-controlled, cross-over study. Insulin secretion and insulin resistance were quantified using the homeostasis model assessment (HOMA) and insulin- stimulated glucose disposal were measured by determining the steady-state p lasma glucose (SSPG). Results The average benefit of metformin was 0.6 mmol/l for glucose (95% co nfidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0 .2-5.4, P = 0.019). Insulin resistance, as quantified by HOMA,was improved by 1.1 (95% CI 0.2-2.0, P = 0.004), without any change in insulin secretion . Basal and insulin-stimulated glucose oxidation were comparable in the pla cebo and metformin-treated groups at the end of each treatment period, as w as the SSPG concentration. However, both systolic and diastolic blood press ures fell significantly following metformin administration as compared to t reatment with placebo. Conclusions These results indicate that metformin administration to patient s with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure. In contrast, neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia.