title: Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial.
abstract: BACKGROUND
  To investigate the long-term efficacy and safety of empagliflozin monotherapy compared with placebo and sitagliptin in drug-naïve patients with type 2 diabetes mellitus.
  
  
  METHODS
  Of 899 patients randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, placebo, or sitagliptin 100 mg once daily for 24 weeks, 615 continued in a double-blind extension trial for ≥52 weeks. Exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76.
  
  
  RESULTS
  Compared with placebo, adjusted mean changes from baseline in HbA1c at week 76 were -0.78 % (95 % CI -0.94, -0.63; p < 0.001) and -0.89 % (95 % CI -1.04, -0.73; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight at week 76 were -1.8 kg (95 % CI -2.4, -1.3; p < 0.001) and -2.0 kg (95 % CI -2.6, -1.5; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to reductions in systolic blood pressure (SBP) compared with placebo in the primary analysis but not in sensitivity analyses. Compared with sitagliptin, empagliflozin 25 mg reduced HbA1c and both empagliflozin doses reduced weight and SBP. Adverse events (AEs) were reported in 76.8, 78.0, 76.4 and 72.2 % of patients on empagliflozin 10 mg, empagliflozin 25 mg, placebo and sitagliptin, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group.
  
  
  CONCLUSIONS
  Empagliflozin monotherapy for ≥76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo.
  
  
  BACKGROUND
  clinicaltrials.gov NCT01289990.
authors.affiliation: Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.|Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.|German Center for Diabetes Research, Partner Düsseldorf, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Diabetes- und Nierenzentrum, Dormagen, Germany. merker@dialyse-dormagen.de.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Merker
authors.affiliation: Boehringer Ingelheim Danmark A/S, Copenhagen, Denmark. anita-vedel.christiansen@boehringer-ingelheim.com.
authors.forename: Anita Vedel
authors.initials: AV
authors.lastname: Christiansen
authors.affiliation: Boehringer Ingelheim France S.A.S., Reims, France. flavien.roux.ext@boehringer-ingelheim.com.
authors.forename: Flavien
authors.initials: F
authors.lastname: Roux
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. afshin.salsali@boehringer-ingelheim.com.
authors.forename: Afshin
authors.initials: A
authors.lastname: Salsali
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. woojae.kim@boehringer-ingelheim.com.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kim
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. peter.stella.hu@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Stella
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. hans-juergen.woerle@boehringer-ingelheim.com.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. uli.broedl@boehringer-ingelheim.com.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C570240:empagliflozin