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Is metformin associated with acute kidney injury? A case-control study of patients with type 2 diabetes admitted with acute infection

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A Correction to this article was published on 15 October 2020

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Abstract

Introduction

Despite the long-term renoprotective effects of Metformin, a recent study on data from the U.S. Food and Drug Administration reported a possible nephrotoxic effect, contributing to the development of acute kidney injury (AKI). We investigated the association between metformin and AKI in patients admitted with the AKI-prone condition of acute infection and compared results with corresponding results of other antidiabetics.

Methods

In a nationwide register-based case–control study, we identified Danish patients with type 2 diabetes hospitalized with acute infection between 2008 and 2018. Cases of AKI had an increase in plasma creatinine ≥  × 1.5 during admission, controls did not. Antidiabetics were identified up to 6 months before admission. Odds ratio (OR) of each antidiabetic was computed in separate multiple logistic regression models adjusted for relevant medication and comorbidities and results compared.

Results

We included 46,811 patients, hereof 9454 AKIs (20%) and 2186 (4.7%) severe AKIs. Overall, 56% were males, median age (IQR) was 73 (65–81). Sixty percent received metformin, 13% sulfonylurea, 31% insulin and 8% dipeptidyl peptidase-4 inhibitors (DPP-4i), with equal distribution between cases and controls. Metformin was associated with increased OR (CI) for AKI, 1.07 (1.02–1.12), equally to sulfonylurea, 1.10 (1.03–1.18) and DPP-4i, 1.11 (1.02–1.20), but not insulin, 0.99 (0.93–1.05). In severe AKI, results for metformin were 1.27 (1.25–1.40) but increased equivalently to other antidiabetics.

Conclusions

In patients with type 2 diabetes hospitalized with acute infection, metformin was not independently associated with AKI, since other antidiabetics were also significantly associated, indicating confounding by indication.

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Code availability

For software use, please see Methods section.

Change history

Abbreviations

AKI:

Acute kidney injury

DPP-4i:

Dipeptidyl peptidase-4 inhibitors

eGFR:

Estimated glomerular filtration rate

IQR:

Interquartile range

RASi:

Renin-angiotensin-system inhibitors

SD:

Standard deviation

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Funding

The authors would like to thank the Gangsted foundation for funding of the study.

Author information

Authors and Affiliations

  1. Department of Cardiology, Herlev and Gentofte Hospital, Kildegaardsvej 28, 2900, Hellerup, Copenhagen, Denmark

    Philip Andreas Schytz, Anders Bonde Nissen, Morten Schou & Gunnar H. Gislason

  2. Department of Medicine, Herlev and Gentofte Hospital, Hellerup, Denmark

    Kristine Hommel

  3. Department of Nephrology, Rigshospitalet, Copenhagen, Denmark

    Karl Emil Nelveg-Kristensen

  4. Department of Research, Hillerod Hospital, Hillerød, Denmark

    Christian Torp-Pedersen

  5. Department of Biostatistics, Copenhagen University, Copenhagen, Denmark

    Thomas A. Gerds

  6. Department of Nephrology, The Danish Heart Foundation and Specialist Registrar, Rigshospitalet, Copenhagen, Denmark

    Nicholas Carlson

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  1. Philip Andreas Schytz
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Contributions

PAS, NC designed the study. PAS performed the data management and prepared the first draft of the manuscript. PAS and TAG conducted the statistical analyses. All authors critically revised the draft manuscript and provided final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Philip Andreas Schytz.

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Conflicts of interest

MS reports lecture grants from Astra Zeneca, Novo, Bohringer and Novartis. The authors declare no potential conflicts of interest with respect to the research, authorship or publication of this article.

Ethics approval

Retrospective, register-based studies do not need prior ethics approval in Denmark. The Danish Data Protection Agency has approved use of data (ref. P-2019–191).

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Please see Methods section.

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The original article has been updated: Due to title udpate.

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Schytz, P.A., Nissen, A.B., Hommel, K. et al. Is metformin associated with acute kidney injury? A case-control study of patients with type 2 diabetes admitted with acute infection. J Nephrol 34, 709–717 (2021). https://doi.org/10.1007/s40620-020-00863-5

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  • DOI: https://doi.org/10.1007/s40620-020-00863-5

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