Lactic acidosis in metformin therapy

The biguanide drugs metformin and phenformin have been linked in the past to lactic acidosis, a metabolic condition associated with high rates of mortality. Although concern over the hyperlactataemic effect of phenformin led to the withdrawal of this drug from clinical practice in the 1970s, the situation with metformin has been less clear. Retrospective data indicate that, in metformin-treated patients with lactic acidosis, neither the degree of hyperlactataemia nor accumulation of metformin is of prognostic significance. Furthermore, the lowest rates of mortality were seen in patients with high plasma concentrations of metformin, which has led to the hypothesis that the drug may confer some benefit, linked to an increase in vasomotility, in such cases. Overall, it appears that mortality in patients receiving metformin who develop lactic acidosis is linked to underlying disease rather than to metformin accumulation, and that metformin can no longer be considered a toxic drug in this respect. These findings are likely to be of considerable relevance to the management of patients with type 2 (non-insulin-dependent) diabetes mellitus, especially where such patients are elderly.