title: Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and tolerability of multiple doses of ipragliflozin. This novel selective inhibitor of sodium glucose co-transporter 2 is in clinical development for the treatment of patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  In a 12-week, multicenter, double-blind, randomized, active- and placebo-controlled dose-finding study, patients were randomized to one of four ipragliflozin treatment groups (12.5, 50, 150, and 300 mg once daily), placebo, or active control (metformin). The primary efficacy outcome was the mean change from baseline to Week 12 of glycosylated hemoglobin (HbA1c) compared with placebo.
  
  
  RESULTS
  Ipragliflozin showed a dose-dependent decrease in HbA1c of -0.49% to -0.81% at Week 12 compared with placebo (P<0.001); a decrease of -0.72% was seen with metformin. Among the ipragliflozin groups there was also a dose-dependent reduction in body weight of up to 1.7 kg. Proportions of patients experiencing treatment-emergent adverse events were similar across all groups: ipragliflozin (45.7-58.8%), placebo (62.3%), and metformin (59.4%). No clinically relevant effects were observed for other safety measures.
  
  
  CONCLUSIONS
  After 12 weeks of treatment, ipragliflozin dose-dependently decreased HbA1c, with ipragliflozin ≥50 mg/day in patients with T2DM; an effect comparable to metformin. No safety or tolerability concerns were identified.
authors.affiliation: Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, LA, USA. vfonseca@tulane.edu
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: John P
authors.initials: JP
authors.lastname: Wilding
authors.forename: Wim
authors.initials: W
authors.lastname: Wilpshaar
authors.forename: Perminder
authors.initials: P
authors.lastname: Dhanjal
authors.forename: Greg
authors.initials: G
authors.lastname: Ball
authors.forename: Sally
authors.initials: S
authors.lastname: Klasen
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D060737:Reproductive Tract Infections / Q000150:complications / Q000453:epidemiology; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000150:complications / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015507:Drugs, Investigational; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049990:Membrane Transport Modulators; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C517652:hemoglobin A1c protein, human; C572941:ipragliflozin