title: Randomized, double-blind, dose-ranging study of TAK-875, a novel GPR40 agonist, in Japanese patients with inadequately controlled type 2 diabetes.
abstract: OBJECTIVE
  Assessment of the efficacy and safety of TAK-875 (a novel GPR40 agonist) in Japanese patients with type 2 diabetes inadequately controlled by diet/exercise.
  
  
  METHODS
  This was a phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week dose-ranging evaluation of TAK-875 (6.25-200 mg once daily) with the primary end point of change in A1C at week 12. A nonblinded group received 1 mg glimepiride once daily as an active control.
  
  
  RESULTS
  A total of 396 patients were randomized to receive TAK-875 (n = 299), placebo (n = 48), or glimepiride (n = 49). The least square mean changes in A1C at week 12 from baseline were as follows: 0.09% in the placebo group; -0.54, -0.67, -0.88, -1.27, -1.29, and -1.40% in the 6.25-, 12.5-, 25-, 50-, 100-, and 200-mg TAK-875 groups, respectively; and -1.32% in the 1-mg glimepiride group. All TAK-875 groups had statistically significant reductions in A1C compared with placebo (P < 0.0001), and those receiving ≥50 mg TAK-875 achieved reductions in A1C equivalent to those with glimepiride. Results for other glycemic parameters, including improvements during a meal tolerance test, mirrored these positive findings with TAK-875. There were no significant differences in incidence of adverse events among the groups and no dose-dependent changes in tolerability. Hypoglycemic episodes were reported in 0.7% of patients in the TAK-875 groups and in 4.1% of the glimepiride group.
  
  
  CONCLUSIONS
  TAK-875 produced clinically and statistically significant improvements in glycemic control in patients with type 2 diabetes inadequately controlled by diet and exercise, and it was well tolerated with a lower propensity to cause hypoglycemia.
authors.affiliation: Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan. kka@med.kawasaki-m.ac.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Takahiro
authors.initials: T
authors.lastname: Araki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yoshinaka
mesh_terms: D000368:Aged; D044466:Asian People; D001572:Benzofurans / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001572:Benzofurans; C473034:FFAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; C557331:TAK-875