Disposition of metformin: Variability due to polymorphisms of organic cation transporters

Abstract

Considerable interindividual variability in clinical efficacy is recognized in the treatment of type 2 diabetes mellitus with the biguanide metformin. Metformin is a substrate of organic cation transporters, which play important roles in gastrointestinal absorption, renal and biliary elimination, and distribution to target sites of substrate drugs. This raises the question of whether genetic variations in these transporters affect efficacy and risk of adverse events associated with metformin use. In this review, the pharmacogenetics of metformin is discussed in the light of the most recent literature. Overall, results from healthy volunteers support the notion that metformin pharmacokinetics can be affected by polymorphisms in genes encoding organic cation transporters. When considering the glycemic response to metformin in patients, however, the likely multifactorial nature of metformin response masks the effects of transporter polymorphisms observed in some clinical studies.

Key words::

• Diabetes mellitus type 2
• genetic polymorphism
• individualized medicine
• metformin
• organic cation transport proteins
• pharmacogenetics
• SLC22A1 transporter
• SLC22A2 transporter
• SLC47A1 transporter
• SLC47A2 transporter

Acknowledgements

I thank MF Fromm for critical reading of the manuscript.

Declaration of interest: The author states no conflict of interest and has received no payment in preparation of this manuscript.