Japan-based Takeda Pharmaceutical’s investigational GPR40 agonist, TAK-875, has lowered HbA1c (blood glucose) levels at doses ranging from 6.25mg to 200mg in Phase 2 trial conducted in patients with type 2 diabetes.
Discovered through orphan G-protein-coupled receptors (GPCRs) research, TAK-875 is a selective agonist of GPR40, one of the GPCRs that are expressed in pancreatic islet cells.
The Phase 2 randomised double-blind placebo and active (glimepiride) comparator-controlled multicentre study was designed to assess once-daily treatment with five different doses of TAK-875 (6.25mg, 25mg, 50mg, 100mg, and 200mg), compared with placebo and glimepiride (2mg-4mg).
In the study, the primary endpoint was changed from baseline in HbA1c levels at week 12, while the secondary endpoints included fasting blood glucose, area under the curve (AUC) for glucose and insulin during an oral glucose tolerance test (OGTT), and body weight.
The data from the trial reported that all doses of TAK-875 showed greater HbA1c reductions at week 12 with reduced treatment-emergent adverse events (TEAE) when compared to placebo.
Takeda metabolic development therapeutic area head Thomas Strack said: "Because of its observed ability to potently stimulate insulin secretion and improve glycemic control with less or no hypoglycemia, these data further support TAK-875 as a potential therapy for the treatment of type 2 diabetes in the future.
"This study, published in The Lancet, demonstrated that activation of the GPR40 receptor may be beneficial in the treatment of type 2 diabetes, without significantly increasing the risk of hypoglycemia, compared to the other drug studied," Strack added.
The trial, conducted by Takeda’s wholly owned subsidiary Takeda Global Research & Development Center, presented the study data at the American Diabetes Association 71st Annual Scientific Sessions.
The company said TAK-875 is the first GPR40 agonist to reach Phase 3 clinical development, and has demonstrated glucose-lowering effects by stimulating glucose-dependent insulin secretion in earlier completed studies.
Image: The Takeda Midosuji Building, headquarters of Takeda Pharmaceutical Company, in Chuo-ku, Osaka, Japan. Photo: J o.