Metabolic Effects of Glucocorticoid and Ethanol Administration in Phenformin‐ and Metformin‐Treated Obese Diabetics

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Abstract
Glucocorticoid administration for 24 hours to phenformin-treated obese diabetics increased blood lactate and lactate/pyruvate (L/P) ratio to higher levels than those found when only one drug was given. In one of 10 subjects, a metabolic acidosis with a blood lactate of 6.2 mmol developed during simultaneous administration of the two drugs. Diabetics treated with phenformin or metformin in equipotent dosages exhibited the highest blood lactate, L/P ratio, and beta-hydroxybutyrate levels during phenformin treatment, both before and during glucocorticoid administration. Ethanol administration to biguanide-treated diabetics resulted in identical increases in blood lactate and L/P ratio during phenformin and metformin treatment. These findings are consistent with the hypothesis that phenformin has a stronger inhibitory effect of gluconeogenesis than metformin. This may be one reason why lactic acidosis is seen much more often in phenformin- than metformin-treated patients.