Metformin-Associated Lactic Acidosis

Abstract

Metformin, the only biguanide available in France, is a widely prescribed anti-diabetic agent. It improves glycemic control by inhibition of gluconeogenesis and its use has shown reduction in morbidity and mortality in type-2 diabetic patients. However, it also affects the lactate metabolism by increasing its production by the cell. Thus, the most serious adverse effect is the onset of a metformin-associated lactic acidosis (MALA). MALA is caused by the accumulation of excessive levels of metformin in the plasma and tissues, either after ingestion of a large amount of the drug, or more frequently in presence of a precipitating factor such as renal insufficiency. In this context of major metabolic acidosis with hyperlactatemia, prognosis is correlated with the severity of organ failure. Treatment is symptomatic with early use of renal replacement therapy in severe forms of the disease. The prevention of MALA is based on the respect of contraindications of metformin in diabetic patients.