Metformin treatment leads to an increase in basal, but not insulin-stimulated, glucose disposal in obese patients with impaired glucose tolerance.
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.
Morel
Y
Y
Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Golay
A
A
Perneger
T
T
Lehmann
T
T
Vadas
L
L
Pasik
C
C
Reaven
G M
GM
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
D001786:Blood Glucose; D002096:C-Peptide; D019270:Fructosamine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010919:Placebos