Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88 ± 21.11 mg/dl to 131.12 ± 16.02 mg/dl after 1 week and to 130.11 ± 13.29 mg/dl after 5 weeks (p<0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33 ± 24.11 mg/dl to 174.66 ± 23.45 mg/dl (p<0.0025) after 1 week and to 177.65 ± 21.71 mg/dl (p<0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p = n.s. after 1 week, p<0.025 after 5 weeks) and serum fructosamine (p<0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and β-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week: insulin binding to monocytes increased slightly but significantly (p<0.05) and the number of receptors per cell rose (p<0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin-related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic guconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.
|Autori:||Gregorio F; Ambrosi F; Marchetti P; Cristallini S; Navalesi R; Brunetti P; Filipponi P.|
|Titolo:||Low dose metformin in the treatment of type II non-insulin-dependent diabetes: clinical and metabolic evaluations.|
|Anno del prodotto:||1990|
|Digital Object Identifier (DOI):||10.1007/BF02581286|
|Appare nelle tipologie:||1.1 Articolo in rivista|