The relation between phenformin therapy and lactic acidosis

Abstract

Two cases of lactic acidosis are described in which the time sequence of events made it certain that phenformin was the precipitating cause. In one patient the condition arose because of self administration of an overdose; in the other, phenformin had been administered to a patient on maintenance dialysis. After recovery, and in the absence of phenformin therapy the second patient was able to clear an intravenous lactate load at a rate similar to that observed in other patients on Chronic dialysis.-A review of the literature re-emphasizes the possible danger of phenformin in the presence of diminished renal or hepatic function, which should be shown to be normal before starting the drug and assessed periodically during therapy.

Phenformin and lactic acidosis.

“…In our study there was no selection bias in favour of phenformin-treated patients and the large proportion of such patients among those with non-ketotic lactic acidosis strongly suggests an important role for the drug. Furthermore, of these 15 patients on phenformin seven had either started the drug or received a dose increase within the month before presentation, a finding similar to that of Cohen et al 2 Nevertheless, clearly there was often associated disease. All non-ketotic patients were azotaemic on presentation, but the presence of underlying renal disease could only be suggested if serum urea or creatinine was raised before presentation, remained raised after recovery, or if necropsy evidence of chronic renal disease was obtained.…”

“…"1 A detailed appraisal of this form of treatment is being prepared.1 2 The other major biguanide drug, metformin, had only rarely been prescribed in the population studied and no case of lactic acidosis was associated with it. Even in France, however, where it is used more extensively reports of associated lactic acidosis have been only sporadic.…”

The effect of short-term administration of antidiabetic biguanide derivatives on the blood lactate levels in healthy subjects

“…However, it has been stressed recently that in some cases phenformin caused development of lactic acidosis despite absence of a predisposing factor and with no increased level of the drug in the blood [26][27][28][29][30]. In this connection it is worth while to emphasize the presence of considerable individual differences observed in our healthy volunteers in their responses to administration of antidiabetic biguanides.…”

Effect of prescribing metformin according to eGFR instead of serum creatinine level: A study based on Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2014

“…Therefore, metformin has been used to treat type 2 diabetes as the first-line oral anti-diabetes drug (OAD) [1]. However, Phenformin, an earlier biguanide, was banned from the market in 1977, because of its devastating side effect namely lactic acidosis, which was associated with more than 50% mortality [2, 3]. Furthermore, there has been a concern that, as a biguanide, metformin would also be associated with this fatal complication.…”