An Update on the Pharmacogenomics of Metformin: Progress, Problems and Potential

Abstract

The increasing prevalence of Type 2 diabetes has emphasized the need to optimize treatment regimens. Metformin, the most widely used oral agent, is recommended as first-line drug therapy by multiple professional organizations. Response to metformin varies significantly at the individual level; this heterogeneity may be explained in part by genetic factors. Understanding these underlying factors may aid with tailoring treatment for individual patients as well as with designing improved Type 2 diabetes therapies. The past 10 years have seen substantial progress in the understanding of the pharmacogenetics of metformin response. The majority of this work has focused on genes involved in the pharmacokinetics of metformin. Owing to the uncertainty surrounding its mechanism of action, studies of pharmacodynamic genetics have been relatively few; genome-wide approaches have the potential to illuminate the molecular details of metformin response. In this review we summarize current knowledge about metformin pharmacogenetics and suggest directions for future investigation.

KEYWORDS::

• antidiabetic
• biguanide
• metformin
• pharmacogenetics
• Type 2 diabetes mellitus

Financial & competing interests disclosure

JN Todd is supported by NIH Training Grant T32 DK007260. JC Florez is supported by National Institute of Diabetes and Digestive and Kidney Diseases grants R01 DK072041 and R01 DK088214 and a Massachusetts General Hospital Scholars Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

JN Todd is supported by NIH National Institutes of Health Training Grant T32 DK007260. JC Florez is supported by National Institute of Diabetes and Digestive and Kidney Diseases grants R01 DK072041 and R01 DK088214 and a Massachusetts General Hospital Scholars Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.