title: Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial.
abstract: BACKGROUND
  We aimed to investigate the efficacy and tolerability of empagliflozin, an oral, potent, and selective inhibitor of sodium-glucose co-transporter 2, in patients with type 2 diabetes who had not received drug treatment in the preceding 12 weeks.
  
  
  METHODS
  In our multicentre, randomised, placebo-controlled, phase 3 trial, we enrolled adults (aged ≥18 years) who had not received oral or injected anti-diabetes treatment in the previous 12 weeks. Eligible patients had HbA1c concentrations of 7-10%. We randomly allocated patients (1:1:1:1) with a computer-generated random sequence, stratified by region, HbA1c, and estimated glomerular filtration rate at screening, to placebo, empagliflozin 10 mg, empagliflozin 25 mg, or sitagliptin 100 mg once daily for 24 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in all randomly allocated patients who were treated with at least one dose of study drug and had a baseline HbA1c value. This study is completed and registered with ClinicalTrials.gov, number NCT01177813.
  
  
  RESULTS
  Between Aug 12, 2010, and March 19, 2012, we randomly allocated 228 patients to receive placebo, 224 to receive empagliflozin 10 mg, 224 to receive empagliflozin 25 mg, and 223 to receive sitagliptin. Compared with placebo, adjusted mean differences in change from baseline HbA1c at week 24 were -0·74% (95% CI -0·88 to -0·59; p<0·0001) for empagliflozin 10 mg, -0·85% (-0·99 to -0·71; p<0·0001) for empagliflozin 25 mg, and -0·73% (-0·88 to -0·59; p<0·0001) for sitagliptin. 140 (61%) patients in the placebo group reported adverse events (four [2%] severe and six [3%] serious), as did 123 (55%) patients in the empagliflozin 10 mg group (eight [4%] severe and eight [4%] serious), 135 (60%) patients in the empagliflozin 25 mg group (seven [3%] severe and five [2%] serious), and 119 (53%) patients in the sitagliptin group (five [2%] severe and six [3%] serious).
  
  
  CONCLUSIONS
  Empagliflozin provides a tolerable and efficacious strategy to reduce HbA1c in patients with type 2 diabetes who had not previously received drug treatment.
  
  
  BACKGROUND
  Boehringer Ingelheim and Eli Lilly.
authors.affiliation: Clinics of Endocrinology and Diabetology, Heinrich-Heine University, Düsseldorf, Germany; German Diabetes Center, Institute for Clinical Diabetology, Düsseldorf, Germany. Electronic address: Michael.Roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Diabetes Institute of Guangdong Province, Key Lab of Diabetology of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Canton, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Eilbracht
authors.affiliation: Boehringer Ingelheim France, Reims, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Delafont
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kim
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D006442:Glycated Hemoglobin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014230:Triazoles; C517652:hemoglobin A1c protein, human; C570240:empagliflozin