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

Ann Med. 2012 Mar;44(2):119-29. doi: 10.3109/07853890.2010.549144. Epub 2011 Mar 3.


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.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Kidney / drug effects*
  • Kidney / metabolism
  • Metformin / pharmacokinetics*
  • Metformin / therapeutic use
  • Organic Cation Transport Proteins / genetics*
  • Organic Cation Transport Proteins / metabolism
  • Polymorphism, Genetic


  • Hypoglycemic Agents
  • Organic Cation Transport Proteins
  • Metformin