Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: a GoDarts study

Connelly, P. J. , Lonergan, M., Soto-Pedre, E., Donnelly, L., Zhou, K. and Pearson, E. R. (2017) Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: a GoDarts study. Diabetes, Obesity and Metabolism, 19(11), pp. 1579-1586. (doi: 10.1111/dom.12978) (PMID:28432751) (PMCID:PMC5655780)

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Aims: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. Materials and Methods: We undertook a population‐based case‐control study of lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994 and 2014. AKI was stratified by severity according to “Kidney Disease: Improving Global Outcomes” guidelines. Mixed‐effects logistic and linear regression were used to analyse lactic acidosis risk and lactate concentrations, respectively. Results: Eighty‐two cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9‐58.3] compared to those not exposed to this drug (11.8 per 100 000 patient years; 95% CI 4.9‐28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin‐exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1: OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001). Conclusions: A clear association was found between metformin, lactate accumulation and the development of lactic acidosis. This relationship is strongest in those with AKI. These results provide robust evidence to support current recommendations to omit metformin in any illness that may precipitate AKI.

Item Type:Articles
Additional Information:Funding: Wellcome Trust New Investigator. Grant Number: 102820/Z/13/Z.
Glasgow Author(s) Enlighten ID:Connelly, Dr Paul
Authors: Connelly, P. J., Lonergan, M., Soto-Pedre, E., Donnelly, L., Zhou, K., and Pearson, E. R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Diabetes, Obesity and Metabolism
ISSN (Online):1463-1326
Published Online:21 April 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Diabetes, Obesity and Metabolism 19(11): 1579-1586
Publisher Policy:Reproduced under a Creative Commons License

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