Metformin-associated lactic acidosis in diabetic patients with acute renal failure. A critical analysis of its pathogenesis and prognosis.

To determine the respective role of metformin accumulation and tissue hypoxia in triggering metformin-associated lactic acidosis (MALA), we measured plasma (PM) and red blood cell (RM) metformin concentrations in 14 patients with MALA and in 58 diabetic patients on well-tolerated chronic metformin treatment. In this control group RM was 0.9 +/- 0.5 mg/l. In MALA, lactic acidosis was of comparable severity whether there was significant cellular metformin accumulation (9 patients with severe renal failure) or not (5 patients with less severe renal failure). Factors of hypoxia were found in all patients except three with isolated anuria and major metformin accumulation. Early mortality was low in patients with metformin accumulation (no rapid death with the exception of two patients with end-stage hepatic failure) whereas it was high in those with metformin accumulation (4 patients died rapidly). In conclusion, MALA is not always associated with metformin accumulation. The prognosis of MALA depends mainly not upon the degree of metformin accumulation but rather upon the severity of hypoxic factors.