Fatal lactic acidosis associated with phenformin therapy

Abstract

The pharmacological action of phenformin, an oral hypoglycaemic agent, differs from other commonly used such agents in that steps in various metabolic pathways are inhibited. Phenformin inhibits NADdependent reactions, and by suppressing the Krebs cycle causes an elevation of blood lactate. If there is renal impairment the drug is retained and the lactic acidosis becomes progressively more severe; death often ensues. Two such cases were described. Firstly, because the patients present with characteristic clinical and laboratory findings, viz. they have maturity onset diabetes and are taking phenformin;they have been vomiting for some days and develop loss of consciousness and hypothemia. They are severely acidotic and hypoglycaemic. Secondly, because the drug’s action is at such a fundamental level and the relationship between laboratory findings and altered intermediary metabolism can be demonstrated.