title: Metformin treatment leads to an increase in basal, but not insulin-stimulated, glucose disposal in obese patients with impaired glucose tolerance.
abstract: OBJECTIVE
  This study was initiated to test the hypothesis that metformin treatment 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, placebo-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 plasma glucose (SSPG).
  
  
  RESULTS
  The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence 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 placebo and metformin-treated groups at the end of each treatment period, as was the SSPG concentration. However, both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo.
  
  
  CONCLUSIONS
  These results indicate that metformin administration to patients 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.
authors.affiliation: Department of Internal Medicine, University Hospital, Geneva, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Morel
authors.forename: A
authors.initials: A
authors.lastname: Golay
authors.forename: T
authors.initials: T
authors.lastname: Perneger
authors.forename: T
authors.initials: T
authors.lastname: Lehmann
authors.forename: L
authors.initials: L
authors.lastname: Vadas
authors.forename: C
authors.initials: C
authors.lastname: Pasik
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D019270:Fructosamine / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D010919:Placebos
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D019270:Fructosamine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010919:Placebos