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. 2017 Nov;19(11):1579-1586.
doi: 10.1111/dom.12978. Epub 2017 Jul 5.

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

Paul J Connelly  1 , Mike Lonergan  1 , Enrique Soto-Pedre  1 , Louise Donnelly  1 , Kaixin Zhou  1 , Ewan R Pearson  1
Affiliations

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

Paul J Connelly et al. Diabetes Obes Metab. 2017 Nov.

Abstract

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.

Keywords: acute kidney injury; database research; lactic acidosis; metformin; type 2 diabetes.

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Conflict of interest statement

All authors declare that there is no duality of interest associated with their contribution to this manuscript.

Figures

Figure 1
Figure 1
Mean lactate concentrations with 95% confidence intervals (CI). Participants were separated into non‐diabetic groups (left), and patients with Type 2 diabetes who were not prescribed metformin (centre) and those who were metformin users (right). Mean lactate concentrations were derived from the all lactate measurements made during the study period within each group
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References

    1. UK Prospective Diabetes Study Group (34) . Effect of intensive blood‐glucose control with metformin on complications in overweight patients with type 2 diabetes. BMJ. 1998;352(UKPDS 34):703‐713. - PubMed
    1. Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double‐blind, placebo‐controlled, dose‐response trial. Am J Med. 1997;103(6):491‐497. - PubMed
    1. Brown JB, Pedula K, Barzilay J, Herson MK, Latare P. Lactic acidosis rates in type 2 diabetes. Diabetes Care. 1998;21(10):1659‐1663. - PubMed
    1. Duong JK, Furlong TJ, Roberts DM, et al. The role of metformin in metformin‐associated lactic acidosis (MALA): case series and formulation of a model of pathogenesis. Drug Saf. 2013;36:733‐746. - PubMed
    1. Silvestre J, Carvalho S, Mendes V, et al. Metformin‐induced lactic acidosis: a case series. J Med Case Rep. 2007;1:126. - PMC - PubMed

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