Fasiglifam

An investigational drug for type 2 diabetes

{{Drugbox | Verifiedfields = changed | verifiedrevid = 477002123 | IUPAC_name = (2S)-2-[[3-[[2-[[4-[[methyl(oxido)amino]methyl]phenyl]amino]acetyl]amino]phenyl]methyl]-1,3-thiazolidine-4-carboxylic acid | image = Fasiglifam.svg | width = 250 | CAS_number = 1000413-72-8 | ATC_prefix = none | PubChem = 16054624 | ChemSpiderID = 17286448 | UNII = 3A9A0X9R6M | KEGG = D09950 | ChEMBL = 2103870 | C=21 | H=23 | N=3 | O=4 | S=1 | smiles = CC1=CC=C(C=C1)N(C)C(=O)C2=CC=CC(=C2)C3C(C(=O)O)NCC3 | StdInChI = 1S/C21H23N3O4S/c1-14-4-6-15(7-5-14)24(2)21(27)16-8-10-17(11-9-16)20-18(19(25)26)12-13-29-20/h4-11,18,20H,12-13H2,1-3H3,(H,25,26) | StdInChIKey = ZQXKQXUSKJHULB-UHFFFAOYSA-N }}

Fasiglifam (also known by its developmental code name TAK-875) is a drug that was under investigation for the treatment of type 2 diabetes mellitus. It was developed by Takeda Pharmaceutical Company and acts as a selective agonist of the G protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1 (FFAR1). Fasiglifam was designed to enhance insulin secretion in response to elevated blood glucose levels, thereby improving glycemic control in patients with type 2 diabetes.

Mechanism of Action

Fasiglifam functions by activating the GPR40 receptor, which is predominantly expressed in pancreatic beta cells. Upon activation by fasiglifam, GPR40 enhances the secretion of insulin in a glucose-dependent manner. This means that insulin is released primarily when blood glucose levels are high, reducing the risk of hypoglycemia, a common side effect associated with some other antidiabetic medications.

Clinical Development

Fasiglifam showed promise in early clinical trials, demonstrating significant improvements in glycemic control with a favorable safety profile. However, during phase III clinical trials, concerns arose regarding potential liver toxicity. In December 2013, Takeda announced the discontinuation of fasiglifam's development due to these safety concerns, despite its efficacy in lowering blood glucose levels.

Safety Concerns

The primary safety concern that led to the discontinuation of fasiglifam was hepatotoxicity. Elevated liver enzymes were observed in some patients, indicating potential liver damage. The exact mechanism of this adverse effect is not fully understood, but it was significant enough to halt further development of the drug.

Potential Impact

Although fasiglifam was not brought to market, its development highlighted the potential of targeting GPR40 as a therapeutic strategy for type 2 diabetes. Research continues in this area, with other compounds being investigated for their ability to safely modulate this receptor and improve insulin secretion.

Also see

• Type 2 diabetes mellitus
• Insulin secretion
• G protein-coupled receptor
• Hepatotoxicity
• Takeda Pharmaceutical Company