title: Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: A 36-week, randomized, double-blind, parallel-group trial.
abstract: OBJECTIVE
  To assess efficacy and safety of liraglutide in combination with insulin compared with insulin monotherapy in Japanese patients with type 2 diabetes.
  
  
  METHODS
  This was a 36-week, multicenter, double-blind, parallel-group trial, where patients on stable insulin therapy (basal/premixed/basal-bolus) were randomized 1:1 to additional liraglutide 0.9 mg/day (n = 127) or placebo (n = 130). The insulin dose was fixed for 16 weeks, and titrated based on self-measured plasma glucose thereafter. The primary end-point was change in glycosylated hemoglobin after 16 weeks.
  
  
  RESULTS
  Superiority of liraglutide plus insulin versus insulin monotherapy was confirmed based on estimated mean difference in glycosylated hemoglobin after 16 weeks of -1.30% (-14 mmol/mol; 95% confidence interval -1.47 to -1.13 [-16, -12]; P < 0.0001). Statistical significance was maintained to week 36. More patients on liraglutide achieved a glycosylated hemoglobin target of <7.0% (<53 mmol/mol) at week 16 (estimated odds ratio 50.57; 95% confidence interval 16.59 to 154.16; P < 0.0001). Improvements in seven-point self-measured plasma glucose and fasting plasma glucose were significantly greater with liraglutide than the placebo at week 16. Insulin dose after 36 weeks was lower with liraglutide than the placebo (estimated treatment ratio: 0.82 [95% confidence interval 0.76-0.90; P < 0.0001]). Occurrence of adverse events was similar in the two groups (85.8 and 81.5%, respectively); most were mild in severity. There were no significant differences in the number of hypoglycemic episodes during the 36 weeks.
  
  
  CONCLUSIONS
  Adding liraglutide to insulin results in superior glycemic control compared with insulin alone in Japanese patients with type 2 diabetes, and is generally well tolerated.
authors.affiliation: Kansai Electric Power Hospital, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.affiliation: Takatsuki Red Cross Hospital, Osaka, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Wasakusa Clinic, Tochigi, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Naka Memorial Clinic, Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
authors.affiliation: Shiraiwa Medical Clinic, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiraiwa
authors.affiliation: Medical & Scientific Affairs Department, Novo Nordisk Pharma Ltd, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nishijima
authors.affiliation: Medical and Science, GLP-1, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Bosch-Traberg
authors.affiliation: Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human
keywords: Insulin; Liraglutide; Type 2 diabetes mellitus