The mechanism of action of phenformin in starved rats

The ability of phenformin to lower the blood glucose concentration after an intraperitoneal glucose load, with a concomitant increase in blood lactate concentration, indicated that the drug was increasing the rate of anaerobic glycolysis. The results of experiments in which glucose and gluconeogenic precursors were given to starved rats were explained by a hypothesis for the mechanism of action of phenformin involving inhibition of certain NAD+-dependent dehydrogenases. Substrates with NAD+-linked oxidations could be discriminated from those, like succinate, with FAD-linked oxidations, and succinate may be of use in the treatment of clinical lacticacidosis caused by biguanide drugs.