Intended for healthcare professionals


Lactic acidosis induced by phenformin is still a public health problem in Italy

BMJ 1997; 315 doi: (Published 29 November 1997) Cite this as: BMJ 1997;315:1466
  1. G Enia, Vice directora,
  2. M Garozzo, Research fellowa,
  3. C Zoccali, Directora
  1. a Centro di Fisiologia Clinica del Consiglio Nazionale delle Ricerche, Reggio Calabria, Italy

    Editor—Phenformin is a well established cause of lactic acidosis, particularly in diabetic patients with renal failure. For this reason, in 1977, the drug was removed from the market in the United States. Since then, only sporadic reports of lactic acidosis induced by phenformin have been published in the North American literature, describing patients who have been prescribed the drug abroad.1 The European Union does not yet have uniform rules for marketing drugs, and though phenformin has been removed from the market in most countries in the union, it is still marketed in Italy. In a Medline survey we found several recent reports of lactic acidosis induced by phenformin in Italian medical journals.2345

    In the past five years in our own centre for kidney diseases we have treated two patients with lactic acidosis induced by phenformin. Both patients had chronic renal failure (serum creatinine concentration 248 and 265 mmol/l) and were taking a combination of phenformin and glibenclamide. The acidosis was severe (bicarbonate concentration 3.8 and 5.8 mmol/l), with a high anion gap (56 and 51 mmol/l). Serum lactate concentration in one of the patients was 20 mmol/l. Serum glucose concentration was low normal in one case (3.7 mmol/l) and moderately high in the other (11.1 mmol/l). Both patients were admitted in shock. One patient was treated with bicarbonate dialysis, and the other with massive infusions of saline and bicarbonate. Both patients recovered after stopping the drug and were well when discharged, with insulin being prescribed instead of oral drugs. Both patients had been referred after several days in medical wards, where phenformin treatment had been maintained. This implies that lactic acidosis induced by phenformin is poorly recognised.

    We suggest that phenformin should be banned from the market in all European countries. In the meantime, doctors working in areas where it is still available must avoid its use, particularly in patients with renal failure. Lactic acidosis induced by phenformin should be suspected everywhere if suggestive symptoms occur in diabetic patients who have travelled in Italy.

    Metformin has been introduced in both the United States and Europe because of its value in the treatment of overweight patients with non-insulin dependent diabetes. This drug has a lower potential for inducing lactic acidosis than phenformin and is considered safe in the general population; however, it remains a serious threat for patients with chronic renal failure.


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