title: Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.
abstract: OBJECTIVE
  To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.
  
  
  METHODS
  This phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24.
  
  
  RESULTS
  At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p < 0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, -0.57% with fasiglifam 25 mg and -0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p < 0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment-emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group.
  
  
  CONCLUSIONS
  Fasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.
authors: Department of Medicine, Kawasaki Medical School, Okayama, Japan.
authors: K
authors: K
authors: Kaku
authors: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: K
authors: K
authors: Enya
authors: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: R
authors: R
authors: Nakaya
authors: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: T
authors: T
authors: Ohira
authors: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors: R
authors: R
authors: Matsuno
mesh_terms: D000368:Aged; D044466:Asian People; D001572:Benzofurans / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003927:Diet, Diabetic; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D001572:Benzofurans; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; C473034:FFAR1 protein, human; C557331:TAK-875; C517652:hemoglobin A1c protein, human
keywords: GPR40; Japanese patients; TAK-875; fasiglifam; type 2 diabetes