Lactic acidosis in metformin-treated patients - Prognostic value of arterial lactate levels and plasma metformin concentrations

Objective: The antidiabetic drug metformin has been associated in a small n umber of patients with lactic acidosis, a serious condition with a poor pro gnosis. However, because of lack of data, the prognostic significance of hy perlactataemia in metformin-treated patients is not known. Methods: Data were collected from 49 metformin-treated patients with lactic acidosis (arterial lactate level greater than or equal to 5 mmol/L and blo od pH less than or equal to 7.35) and available plasma metformin concentrat ion data to investigate the association of arterial lactate levels and plas ma metformin concentrations with mortality. Results: The overall mortality rate in this patient sample was 45% and the median arterial lactate level was 13.1 mmol/L. Median lactate levels were s imilar in patients who survived (13 mmol/L) and those who died (14.3 mmol/L ), whereas the median plasma metformin concentration was 3 times higher in patients who survived (20.6 mg/L versus 6.3 mg/L). Conclusion: In this, the largest series of metformin-treated patients with lactic acidosis yet reported, 55% of patients survived and these patients h ad a median arterial lactate level of 13.1 mmol/L. Neither arterial lactate levels nor plasma metformin concentrations were of prognostic significance in relation to mortality in this sample of metformin-treated patients with lactic acidosis. Death in these patients appeared instead to be associated with other hypoxic disease or underlying ill health. These observations su ggest that accumulation of metformin may not be as significant with respect to high arterial levels of lactate and their effects as has been tradition ally thought.