SHORT ADMINISTRATION OF METFORMIN IMPROVES INSULIN SENSITIVITY IN ANDROID OBESE SUBJECTS WITH IMPAIRED GLUCOSE-TOLERANCE

In a double-blind, randomized, cross-over study, the metabolic effects of a short treatment with metformin (2 x 850 mg day(-1) for 2 days and 850 mg 1 h before evaluation) were compared to those of placebo in 15 obese subjects (BMI: 33.2 +/- 0.9 kg m(-2)), with abdominal distribution of adipose tissue and impaired glucose tolerance. An intravenous glucose tolerance test (0.3 g glucose kg(-1)) was performed after each period of treatment. Areas under the curve (AUC(0-180 min)) were calculated for plasma glucose, insulin, and C-peptide levels. Glucose tolerance was estimated by the coefficient of glucose assimilation (K-G). Insulin sensitivity (S-I) and glucose effectiveness (S-G) indices were calculated using Bergman's minimal model. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate (MCR) was estimated by dividing AUC ISR by AUC insulin. Easting plasma insulin levels were reduced after metformin (89.3 +/- 15.9 vs 112.4 +/- 24.3 pmol l(-1); p = 0.04). AUC glucose, K-G and S-G were similar in both tests. However, AUC insulin was reduced (39.7 +/- 6.5 vs 51.8 +/- 10.4 nmol min l(-1); p = 0.02), while S-I (6.98 +/- 1.14 vs 4.61 +/- 0.42 10(-5) min(-1) pmol(-1) l; p = 0.03) and insulin MCR (715 +/- 116 vs 617 +/- 94 ml min(-1) m(-2); p = 0.03) were increased after metformin. The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in android obese subjects with impaired oral glucose tolerance.