Introduction: Metformin is recommended as first-line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter genes have shown effects on metformin pharmacokinetics and pharmacodynamics. Areas covered: This article provides a review of the current status of the influence of transporter pharmacogenomics on metformin efficacy and tolerability. The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Conversely, genome-wide association studies of metformin response have identified signals in the pharmacodynamic pathways rather than the transporters involved in metformin disposition. Currently, pharmacogenomic testing to predict metformin response and tolerability may not have a clinical role, but with additional data from larger studies and availability of safe and effective alternative antidiabetic agents, this is likely to change.
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