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Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study

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Abstract

Background

Metformin has pleiotropic effects including anti-inflammatory properties and effects on the gut microbiome. It is primarily used in the older population, where the occurrence of inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine whether metformin protects against development of IBD.

Methods

In the setting of a Danish nationwide population-based cohort, we conducted a nested case–control study using a new-user active comparator design. For each patient with IBD, we selected 10 IBD-free individuals matched on age, sex, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) of IBD. Adjustment included educational level, other immune-mediated inflammatory diseases, and use of dipeptidyl peptidase (DPP)-4 inhibitors and statins.

Results

Among 302,863 IBD-free new users of oral glucose-lowering drugs, we identified 1271 patients who developed IBD and 12,676 matched IBD-free individuals. Mean age at IBD diagnosis was 66 (SD, 11) years. We found no association between ever use of metformin and risk of IBD, Crohn’s disease or ulcerative colitis, adjusted OR 0.95 (95% CI 0.78–1.15), 0.87 (95% CI 0.60–1.26), and 1.04 (95% CI 0.83–1.31), respectively. Neither was the cumulative dose of metformin or the treatment duration with metformin associated with risk of IBD.

Conclusions

In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD.

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Data availability

The study is based on data from the Danish nationwide registers (https://sundhedsdatastyrelsen.dk). The register data are protected by the Danish Act on Processing of Personal Data and are accessed through application to and approval from the Danish Data Protection Agency and the Danish Health Data Authority.

Abbreviations

CD:

Crohn’s disease

CI:

Confidence interval

HR:

Hazard ratio

IBD:

Inflammatory bowel disease

ICD:

International classification of diseases

IQR:

Interquartile range

PY:

Person-years

UC:

Ulcerative colitis

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Acknowledgements

This work was supported by The Novo Nordisk Foundation [grant number NNF16OC0022586] and The Danish National Research Foundation [Grant no. DNRF148]. These had no role in the study design or in the collection, analysis, and interpretation of data.

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Authors and Affiliations

  1. Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, A.C. Meyers Vænge 15, 2450, Copenhagen, Denmark

    Kristine H. Allin & Tine Jess

  2. Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark

    Kristine H. Allin & Tine Jess

  3. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark

    Camilla B. Jensen & Rikke K. Jacobsen

Authors
  1. Kristine H. Allin
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  2. Camilla B. Jensen
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  4. Tine Jess
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Contributions

KHA study concept, study design, interpretation of data, writing up of the first draft of the paper, critical revision of the manuscript for important intellectual content. CBJ study design, data analysis, interpretation of data, critical revision of the manuscript for important intellectual content. RKJ study design, data analysis, interpretation of data, critical revision of the manuscript for important intellectual content. TJ study concept, study design, interpretation of data, critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Kristine H. Allin.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The study was approved by the Danish Data Protection Agency, and data were analyzed on a secure research server at Statistics Denmark. Ethical approval is not required for registry-based research in Denmark.

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Allin, K.H., Jensen, C.B., Jacobsen, R.K. et al. Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study. J Gastroenterol 57, 761–769 (2022). https://doi.org/10.1007/s00535-022-01896-2

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  • DOI: https://doi.org/10.1007/s00535-022-01896-2

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