E-corrected QT interval; QTcN [ms]: Population heart rate-corrected QT interval; RMC: Repeated measurements crossover model; RR [ms]: Interval amongst subsequent R waves; SE: Regular error; SGLT2: Sodium glucose cotransporter two; T2DM: Form two diabetes mellitus; tmax [h]: Time from (last) dosing to Cmax; TQT: Thorough QT study. Competing interests AR, TB, SM, GS, HJW and UCB were staff of Boehringer Ingelheim at the time of conduct and reporting with the study; BW and KBG have been contracted by Boehringer Ingelheim for analysis and reporting. Authors’ contribution The authors meet criteria for authorship as advisable by the International Committee of Medical Journal Editors (ICMJE), had been totally responsible for all content and editorial choices, had been involved at all stages of manuscript improvement, and have approved the final version. AR, TB, SM, HJW and UCB developed the study. AR, KBG, GS, BW, TB and SM released the statistical analysis program. AR, GS and BW have been accountable for the statistical analyses. All authors participated inside the preparation from the clinical trial report. All authors read and authorized the final manuscript. Acknowledgements The study was funded by Boehringer Ingelheim. Assays for plasma concentrations of empagliflozin had been performed by Bioanalytical Systems, Inc., West Lafayette, IN, USA. Authors acknowledge Lois Rowland forReferences 1. Mather A, Pollock C: Glucose handling by the kidney. Kidney Int 2011, 79:S1 six. two. DeFronzo RA, Davidson JA, Del Prato S: The part on the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012, 14:five?four. 3. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF: Effect of dapagliflozin in patients with sort 2 diabetes that have inadequate glycaemic manage with metformin: A randomised, double-blind, placebo-controlled trial. Lancet 2010, 375:2223?233. four. Schwartz SL, Akinlade B, Klasen S, Kowalski D, Zhang W, Wilpshaar W: Safety, pharmacokinetic, and pharmacodynamic profiles of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium-dependent glucose co-transporter two, in sufferers with variety two diabetes mellitus. Diabetes Technol Ther 2011, 13:1219?227. 5. Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W: Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter two inhibitor, as add-on to metformin in subjects with sort 2 diabetes. Diabetes Care 2012, 35:1232?238. six. Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ: A phase IIb, randomised, placebo-controlled study of the SGLT2 inhibitor empagliflozin in sufferers with variety 2 diabetes. Diabetes Obes Metab 2013.1346245-52-0 uses doi:10.1S,2S-DHAC-Phenyl Trost Ligand Purity 1111/dom.PMID:23724934 12081 [Epub ahead of print]. 7. Katsiki N, Papanas N, Mikhailidis DP: Dapagliflozin: Much more than just one more oral glucose-lowering agent? Specialist Opin Investig Drugs 2010, 19:1581?589. 8. Rosenstock J, Jelaska A, Seman L, Pinnetti S, Hantel S, Woerle HJ: Efficacy and security of BI 10773, a brand new sodium glucose cotransporter (SGLT-2) inhibitor, in form two diabetes inadequately controlled on metformin. [abstract]. Diabetes 2011, 60:A271 [989-P]. 9. Grempler R, Thomas L, Eckhardt M, Himmelsbach F, Sauer A, Sharp D, Bakker M, Klein T, Eickelman P: Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab 2012, 14:83?0. 10. Seman L, Macha S, Nehmiz G, Simons G, Ren B, Pinnetti S, Woerle HJ, Dugi K.