Diabetologia (2012) 55:1971–1977 We have shown, by additional replication and meta- analysis, that our initial report is consistent in multiple populations, supporting the finding that variation at the ATM locus is the most robust metformin response variant to date. Our data further support the notion that genetic variation does not only affect disease susceptibility, but also affects treatment response. Given the currently sparse efforts to elucidate the genetic architecture of type 2 diabetes treat- ment response, our data imply that future large-scale well- powered studies might be successful in identifying further novel loci affecting treatment response. This is particularly pertinent for metformin response, where the biology of its working mechanism is not fully elucidated. It is clear that additional research is required to establish that rs11212617 is the causal SNP and that the ATM gene is the causal gene at this locus. In addition, it is necessary to investigate the mechanism whereby ATM variation alters metformin response. Acknowledgements We are grateful to all the participants in this study, to the general practitioners, to the Scottish School of Primary Care for their help in recruiting the participants, and to the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, reception- ists and nurses. Funding The work in this study was financially supported by the Dutch Diabetes Research Foundation grant 2006.00.060. The Wellcome Trust provides support for the Wellcome Trust UK Type 2 Diabetes Case Control Collection (GoDARTS) and infor- matics support is provided by the Chief Scientist Office. The Wellcome Trust funds the Scottish Health Informatics Programme, provides core support for the Wellcome Trust Centre for Human Genetics in Oxford, and funds the Wellcome Trust Case Control Consortium 2. This research was specifically funded by Diabetes UK (07/0003525). N. van Leeuwen is a member of the Interna- tional Research Training Group (IRTG) funded by the DFG (GRH 1389/1) and NWO (grant DN95-420). K. Zhou holds a Henry Wellcome Post-Doctoral Fellowship. Duality of interest R.R. Holman received research support from Amylin, Bayer, Merck and Novartis, attended advisory boards with Amylin, Lilly, Merck, Novartis and Novo Nordisk, and gave lectures supported by Bayer, Lilly Merck and Merck Serono. H. Colhoun received research support from Pfizer Inc., Roche Pharmaceuticals, Boehringer Ingelheim, Astrazeneca, Eli Lilly & Company, attended advisory boards with sanofi-aventis, Pfizer Inc., Novartis Pharmaceut- icals, Elis Lilly & Company, received lecture fees from Pfizer Inc., and is a Stock/Shareholder of Roche Pharmaceuticals. The other authors declare that there is no duality of interest associated with this manuscript. 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