Phase 2 clinical data of an investigational type 2 diabetes therapy, TAK-875 of Takeda Pharmaceutical Company Limited ("Takeda"), were published online first in The Lancet. The clinical trial was conducted by Takeda's wholly owned subsidiary, Takeda Global Research & Development Center, Inc. in Deerfield, Illinois. These data, which were presented at the American Diabetes Association 71st Annual Scientific Sessions, demonstrated that the GPR40 agonist, at doses ranging from 6.25 to 200 mg a day, met its primary endpoint of statistically significantly lowering HbA1c (blood glucose) levels over a 12-week period versus placebo. This was achieved without significant increase in the incidence of hypoglycemia (low blood sugar) compared to placebo.
Discovered by Takeda, through orphan G-protein-coupled receptors (GPCRs) research, TAK-875 is the first GPR40 agonist to reach late stage (Phase 3) clinical development, and completed studies have demonstrated glucose-lowering effects in patients with type 2 diabetes by stimulating glucose-dependent insulin secretion.
"As glucose control in many patients with type 2 diabetes continues to remain suboptimal, it is important to work to identify new mechanisms of action in an effort to improve treatment options," said Thomas Strack, M.D., development therapeutic area head, metabolic, Takeda. "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."
Agonists of GPR40, one of the GPCRs expressed in pancreatic islet cells, have a mechanism of stimulating insulin in a glucose-dependent manner, which is different from other diabetes drug classes, e.g., sulfonylureas.
"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," added Strack. "Takeda remains committed to developing new medications and working to improve therapeutic care. These clinical data validate the opportunity to further evaluate this different compound for the treatment of type 2 diabetes."
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