Metformin-related lactic acidosis: is it a myth or an underestimated reality?
Metformin, 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.
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Luca
L
Visconti
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Valeria
V
Cernaro
b Unit of Nephrology, Ospedali Riuniti Villa Sofia, Cervello , Palermo , Italy.
Domenico
D
Ferrara
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Giuseppe
G
Costantino
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Carmela
C
Aloisi
b Unit of Nephrology, Ospedali Riuniti Villa Sofia, Cervello , Palermo , Italy.
Luisa
L
Amico
c Department of Pediatric Sciences , University of Messina , Messina , Italy.
Valeria
V
Chirico
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Domenico
D
Santoro
d Department of Neuroscience and Anesthesiology , University of Messina , Messina , Italy.
Alberto
A
Noto
d Department of Neuroscience and Anesthesiology , University of Messina , Messina , Italy.
Antonio
A
David
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Michele
M
Buemi
a Chair of Nephrology, Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy.
Antonio
A
Lacquaniti
D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects; D008687:Metformin / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D017582:Renal Replacement Therapy; D012307:Risk Factors
D007004:Hypoglycemic Agents; D008687:Metformin
Metformin-associated lactic acidosis (MALA); acute kidney injury; continuous renal replacement therapy; hemodialysis; lactic acidosis; metformin