An update on the pharmacogenomics of metformin: progress, problems and potential

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.