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A Comprehensive Review of Drug–Drug Interactions with Metformin

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Abstract

Metformin is the world’s most commonly used oral glucose-lowering drug for type 2 diabetes, and this is mainly because it protects against diabetes-related mortality and all-cause mortality. Although it is an old drug, its mechanism of action has not yet been clarified and its pharmacokinetic pathway is still not fully understood. There is considerable inter-individual variability in the response to metformin, and this has led to many drug–drug interaction (DDI) studies of metformin. In this review, we describe both in vitro and human interaction studies of metformin both as a victim and as a perpetrator. We also clarify the importance of including pharmacodynamic end points in DDI studies of metformin and taking pharmacogenetic variation into account when performing these studies to avoid hidden pitfalls in the interpretation of DDIs with metformin. This evaluation of the literature has revealed holes in our knowledge and given clues as to where future DDI studies should be focused and performed.

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Acknowledgments

The Danish Council for Independent Research|Medical Science provided financial support for this study (protocol number 12-126791).

Conflicts of interest

Tore Bjerregaard Stage has given paid lectures for Astellas Pharma, Orifarm, Novartis and Eisai. None of the other authors has any relevant conflicts of interest to declare.

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  1. Clinical Pharmacology, Department of Public Health, University of Southern Denmark, J.B. Winsloews vej 19, 2nd Floor, 5000, Odense, Denmark

    Tore Bjerregaard Stage, Kim Brøsen & Mette Marie Hougaard Christensen

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  1. Tore Bjerregaard Stage
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  2. Kim Brøsen
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Correspondence to Tore Bjerregaard Stage.

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Stage, T.B., Brøsen, K. & Christensen, M.M.H. A Comprehensive Review of Drug–Drug Interactions with Metformin. Clin Pharmacokinet 54, 811–824 (2015). https://doi.org/10.1007/s40262-015-0270-6

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