Metformin-induced lactic acidosis: potentiation by ethanol

Although lactic acidosis has been recognized as a potential hazard in biguanide therapy, this complication has been claimed to be extremely rare with dimethylbiguanide (DMBG) (metformin). 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 (3.5-13 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 two 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. These results indicate that: (1) doses of DMBG which produce hypoglycemia are associated with lactic acidosis, and (2) this effect of DMBG can be markedly potentiated by ethanol.