The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis
Abstract
BACKGROUND: Lactic acidosis is an adverse event associated with metformin usage. Patients with metformin-associated lactic acidosis (MALA), however, often have other conditions contributing to the event. The relative contribution of metformin is often unclear. MALA is usually diagnosed without measuring the plasma concentrations of metformin.
OBJECTIVES: The objectives of this study were, first, to examine the plasma concentrations of metformin, lactate and creatinine and the arterial pH of patients with suspected MALA and, second, to review critically the mechanisms of MALA.
METHODS: Patients who were suspected of having MALA were identified during the period October 2008-September 2011. Repeated blood samples were collected to determine the plasma concentrations of lactate, metformin and creatinine. The pH of arterial blood was also measured on several occasions in each patient.
RESULTS: Patients (n = 15; 9 female, 6 male) were 70 ± 12 years of age. There was one acute metformin overdose (estimated dose 5 g). Metformin was undetectable in one patient and one patient had therapeutic concentrations of metformin on admission (<5 mg/L). There were ten patients with chronic kidney disease, whereby the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m(2) before the acidotic event. Metformin doses ranged from 1 to 3 g daily (excluding the deliberate overdose). On admission, the mean plasma concentration of metformin on admission was 29.8 ± 19.1 mg/L (mean…
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