title: 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.
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.
authors.affiliation: Department of Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaku
authors.affiliation: Japan Development Center, Takeda Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Enya
authors.affiliation: Japan Development Center, Takeda Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Nakaya
authors.affiliation: Japan Development Center, Takeda Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohira
authors.affiliation: Japan Development Center, Takeda Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Matsuno
mesh_terms: D001572:Benzofurans / Q000627:therapeutic use*; D001645:Biguanides / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007564:Japan; D008099:Liver; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D013450:Sulfones / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001572:Benzofurans; D001645:Biguanides; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C473034:FFAR1 protein, human; C557331:TAK-875; C517652:hemoglobin A1c protein, human
keywords: FFA1 receptor agonist; GPR40 agonist; TAK-875; fasiglifam; type 2 diabetes mellitus