A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT

Aim: To determine the influence of polymorphisms on the effects of metformin on HbA1c, daily dose of insulin and metformin plasma concentration. Methods: In a post hoc analysis of a 4.3 year placebo-controlled randomized trial with 390 patients with Type 2 diabetes already on insulin, we analyzed the influence of polymorphisms in genes coding for ATM and the transporters OCT1 and MATE1. Outcome measures were a combined HbA1c + daily dose of insulin Z score and metformin plasma concentrations. Results: rs11212617 (ATM) was associated with an improved Z score and a lower metformin plasma concentration. In addition, the major allele of rs2289669 (MATE1) was also associated with an improved Z score. Conclusion: The ATM SNR rs11212617 significantly affected the effect of metformin and metformin plasma concentration. Further research is needed to determine the clinical importance of these findings, in particular the effects on metformin plasma concentration.