METFORMIN-INDUCED LACTIC-ACIDOSIS - POTENTIATION BY ETHANOL

  • 1 January 1981
    • journal article
    • research article
    • Vol. 33  (1) , 21-31
Abstract
[Phenformin(1-betaphenethylbiguanide) and metformin (1,1-dimethylbiguanide, DMBG) are used to treat maturity-onset diabetes mellitus in humans.]. Although lactic acidosis was recognized as a potential hazard in biguanide therapy, this complication was claimed to be extremely rare with DMBG. In the present studies, using the fasted guinea pig, DMBG (125-500 mg/kg i.p.) caused marked dose-related changes in both plasma glucose (43-88% reduction) and blood lactate (3.5- to 13-fold increase). Lactate/pyruvate ratios were substantially increased. While i.p. doses of 100 mg/kg of DMBG or of 1 g/kg of ethanol produced no changes in plasma glucose, lactate or pyruvate, the 2 drugs administered conjointly at the indicated doses produced a 53% decrease in plasma glucose and 2- and 10-fold increases in pyruvate and lactate levels, respectively, and correspondingly, an increase in the lactate/pyruvate ratio. Ethanol decay curves indicated that DMBG did not significantly influence the disappearance of ethanol from the blood. Doses of DMBG which produce hypoglycemia are associated with lactic acidosis, and this effect of DMBG can be markedly potentiated by ethanol.