Long-term safety and efficacy of fasiglifam (TAK-875), a G-protein-coupled receptor 40 agonist, as monotherapy and combination therapy in Japanese patients with type 2 diabetes: a 52-week open-label phase III study

Diabetes Obes Metab. 2016 Sep;18(9):925-9. doi: 10.1111/dom.12693. Epub 2016 Jun 29.

Abstract

This multicentre, open-label, phase III study investigated the safety and efficacy of the G-protein-coupled receptor 40 agonist fasiglifam. Japanese patients with type 2 diabetes and inadequate glycaemic control despite diet and/or exercise (n = 282), or despite diet and/or exercise plus one oral antidiabetic agent [sulphonylurea (n = 262), rapid-acting insulin secretagogue (n = 124), α-glucosidase inhibitor (n = 141), biguanide (n = 136), thiazolidinedione (n = 139) or dipeptidyl peptidase-4 inhibitor (n = 138)] were randomized to treatment with fasiglifam 25 or 50 mg once daily for 52 weeks. The primary endpoints were safety variables. The overall incidence of treatment-emergent adverse events (TEAEs) was 75.4-85.1% in the 25 mg group and 78.9-89.9% in the 50 mg group; most TEAEs were mild. Hypoglycaemia was negligible with fasiglifam monotherapy and most common with sulphonylurea combination therapy (12.4 and 9.1% for 25 and 50 mg groups, respectively). Abnormal liver-related laboratory values were uncommon. Glycated haemoglobin levels decreased from week 2 in all groups and were maintained to week 52. Although fasiglifam as monotherapy or in combination regimens was well tolerated during long-term treatment, global concerns about liver safety led to termination of its development after study completion.

Keywords: FFA1 receptor agonist; GPR40 agonist; TAK-875; fasiglifam; type 2 diabetes mellitus.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / therapeutic use*
  • Biguanides / therapeutic use
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / metabolism
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Humans
  • Hypoglycemia / chemically induced
  • Japan
  • Liver
  • Male
  • Middle Aged
  • Receptors, G-Protein-Coupled / agonists
  • Sulfones / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome

Substances

  • Benzofurans
  • Biguanides
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • FFAR1 protein, human
  • Glycated Hemoglobin A
  • Glycoside Hydrolase Inhibitors
  • Receptors, G-Protein-Coupled
  • Sulfones
  • Sulfonylurea Compounds
  • TAK-875
  • Thiazolidinediones
  • hemoglobin A1c protein, human