• Luca Visconti, Valeria Cernaro, Domenico Ferrara, Giuseppe Costantino, Carmela Aloisi, Luisa Amico, Valeria Chirico, Domenico Santoro, Alberto Noto, Antonio David, Michele Buemi, and Antonio Lacquaniti.
• a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
• Ren Fail. 2016 Oct 1; 38 (9): 1560-1565.

AbstractMetformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma metformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating metformin as the cause of lactic acidosis if low plasma levels occurred. Renal replacement therapies have been successfully employed to achieve the correction of metabolic acidosis and rapidly remove metformin and lactate, but the optimal treatment modality for MALA is still controversial.

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