title: Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes.
abstract: OBJECTIVE
  Sulphonylureas (SUs) are often used as first-line treatments for type 2 diabetes in Japan, hence it is important to study new antidiabetic drugs in combination with SUs in Japanese patients.
  
  
  METHODS
  The efficacy and safety of the once-daily human glucagon-like peptide-1 (GLP-1) analogue liraglutide were compared in 264 Japanese subjects [mean body mass index (BMI) 24.9 kg/m(2); mean glycated haemoglobin (HBA1c) 8.4%] randomized and exposed to receive liraglutide 0.6 mg/day (n = 88), 0.9 mg/day (n = 88) or placebo (n = 88) each added to SU monotherapy (glibenclamide, glicazide or glimeprimide) in a 24-week, double-blind, parallel-group trial.
  
  
  RESULTS
  The mean change in HBA1c from baseline to week 24 (LOCF) was -1.56 (s.d. 0.84) and -1.46 (s.d. 0.95) with liraglutide 0.9 and 0.6 mg respectively, and -0.40 (s.d. 0.93) with placebo. HBA1c decreased in the placebo group from 8.45 to 8.06%, while liraglutide reduced HBA1c from 8.60 to 7.14%, and from 8.23 to 6.67% at the 0.6 and 0.9 mg doses respectively. Mean HBA1c at week 24 of the two liraglutide groups were significantly lower than the placebo group (p < 0.0001 for both). More subjects reached HBA1c < 7.0% with liraglutide (0.6 mg: 46.5%; 0.9 mg: 71.3%) vs. placebo (14.8%). Fasting plasma glucose (FPG) levels were significantly improved with liraglutide (difference -1.47 mmol/l and -1.80 mmol/l with 0.6 and 0.9 mg vs. placebo; p < 0.0001). Overall safety was similar between treatments: no major hypoglycaemic episodes were reported, while 84/77/38 minor hypoglycaemic episodes occurred in the 0.6 mg/0.9 mg and placebo treatment groups (all in combination with SU), reflecting lower ambient glucose levels. No relevant change in mean body weight occurred in subjects receiving liraglutide (0.6 mg: 0.06 kg; 0.9 mg: -0.37 kg), while mean body weight decreased in subjects receiving placebo (-1.12 kg).
  
  
  CONCLUSIONS
  The addition of liraglutide to SU treatment for 24 weeks dose-dependently improved glycaemic control vs. SU monotherapy, without causing major hypoglycaemia or weight gain or loss.
authors.affiliation: Diabetes and Endocrine Division, Department of Medicine, Kawasaki Medical School, Okayama 701-0192, Japan. kka@med.kawasaki-m.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kaku
authors.forename: M F
authors.initials: MF
authors.lastname: Rasmussen
authors.forename: P
authors.initials: P
authors.lastname: Clauson
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D044466:Asian People; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D010919:Placebos; D013453:Sulfonylurea Compounds