title: Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study.
abstract: BACKGROUND
  Trelagliptin is a novel once-weekly oral DPP-4 inhibitor. We assessed the efficacy and safety of trelagliptin versus the daily oral DPP-4 inhibitor alogliptin in Japanese patients with type 2 diabetes.
  
  
  METHODS
  We did a randomised, double-blind, active-controlled, parallel-group, phase 3, non-inferiority study at 26 sites in Japan. We included individuals with type 2 diabetes inadequately controlled by diet and exercise. We randomly assigned patients (2:2:1) to receive trelagliptin (100 mg) once per week, alogliptin (25 mg) once per day, or placebo for 24 weeks. Randomisation was done electronically and independently from the study with permuted blocks of ten patients. Patients and clinicians were masked to group assignment. Patients in the trelagliptin group were given trelagliptin once a week and oral alogliptin placebo every day, whereas patients in the alogliptin group were given oral trelagliptin placebo once a week and oral alogliptin every day (double-dummy design). Patients in the placebo group were given an oral alogliptin placebo once a day and an oral trelagliptin placebo once a week. Our primary outcome was between-groups difference in change in HbA1c concentration from baseline to the end of treatment. The non-inferiority margin was 0·4%. Our analysis included all patients who were randomised and received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT01632007.
  
  
  RESULTS
  Between May 26, 2012, and Nov 20, 2012, we enrolled 357 patients. 243 patients were included in the analysis (101 for trelagliptin, 92 for alogliptin, and 50 for placebo). In the primary analysis, the least squares mean change in HbA1c concentration was -0·33% in the trelagliptin group (SE 0·059) and -0·45% in the alogliptin group (0·061) based on the ANCOVA model. The least squares mean difference (trelagliptin minus alogliptin) of change from baseline in HbA1c concentration was 0·11% (95% CI -0·054 to 0·281). Trelagliptin was non-inferior to alogliptin. Both active groups had significantly reduced mean HbA1c concentrations at end of treatment compared with placebo (p<0·0001). The frequency of adverse events was similar between groups. No hypoglycaemia was reported with trelagliptin and the drug was well tolerated.
  
  
  CONCLUSIONS
  The once-weekly DPP-4 inhibitor trelagliptin showed similar efficacy and safety to alogliptin once daily in Japanese patients with type 2 diabetes. Trelagliptin could be a useful new antidiabetes drug that needs to be given once a week.
  
  
  BACKGROUND
  Takeda Pharmaceutical Company.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: inagaki@metab.kuhp.kyoto-u.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Onouchi
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Maezawa
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company, Osaka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Kawasaki Medical School, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000284:Administration, Oral; D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D006442:Glycated Hemoglobin; D010880:Piperidines; D014498:Uracil; C517652:hemoglobin A1c protein, human; C520853:alogliptin; C000595449:trelagliptin