We report a case of severe biguanide-induced lactic acidosis which did not respond to symptomatic alkali treatment via either intravenous bicarbonate infusion or bicarbonate-dialysis. We thus initiated a therapeutic strategy based on insulin and thiamine only in order to reactivate the pyruvate oxidative pathway, in which both drugs play important roles as cofactors. This original "physiological" approach proved effective, and further alkali administration was unnecessary. Our results prompted a review of the literature on the treatment of biguanide-induced lactic acidosis, a situation in which the absence of precise therapeutic rules can undoubtedly affect both the evolution and the prognosis of the syndrome.