Sunday , December 17 2017
Home / Resources / Articles / New Target Shows Promise for Type 2 Diabetes

New Target Shows Promise for Type 2 Diabetes

An investigational first in class compound with a novel mechanism of action appears to improve glycemic control in type 2 diabetes.

Patients on several different doses of TAK-875 lowered their HbA1c at rates comparable to those on glimepiride, Prabhakar Viswanathan, MD, PhD, of Takeda Global Research and Development, reported at the American Diabetes Association

The dose effect appears to plateau at around 50 mcg, Viswanathan said. The drug is a selective G-protein-coupled receptor 40 (GPR40) agonist, and is the first in its class to reach clinical development.

G-protein-coupled receptors are expressed in pancreatic islet cells, and the goal of this drug is to modulate them to selectively improve glucose-dependent insulin secretion, Viswanathan explained.

He and his colleagues conducted a randomized, double-blind, placebo and active control, parallel-group, multicenter study to evaluate the GPR40 agonist’s safety and efficacy at five doses (6.25 mcg, 25 mcg, 50 mcg, 100 mcg, and 200 mcg) over 12 weeks.

About 75% of the 426 patients were also on background metformin. The primary endpoint was change in baseline HbA1c at week 12, and other endpoints including changes in A1c over time, fasting plasma glucose, oral glucose tolerance, and incidence of hypoglycemia.

Viswanathan and colleagues found that patients on all doses of the drug had greater reductions in HbA1c than did those on placebo — and those on 50 mcg or more had declines comparable to that of glimepiride.

Twice as many patients treated with more than 25 mcg had an HbA1c below 7% by the end of the study, Viswanathan added. He also noted that changes from baseline in fasting plasma glucose and an oral glucose tolerance test were consistent with changes in HbA1c.

Viswanathan said beta cell function also appeared to improve, as HOMA-beta scores were significantly higher for those on 50 mcg of the drug or more compared with placebo (P<0.05).

The incidence of hypoglycemia was significantly lower in all of the TAK-875 groups than in the glimepiride group and was similar to the incidence seen in the placebo group (2.3% versus 16.1% versus 3.3%).

Discontinuations because of adverse events were low and similar among all active treatment groups, Viswanathan said.

The results, he concluded, “support further evaluation of this novel compound in the treatment of type 2 diabetes.”

Clifford Bailey, PhD, of Aston University in Birmingham, England, said more efforts are being concentrated on improving beta-cell function in type 2 diabetes, and G-protein-coupled receptors are one of those targets. He noted that these receptors are normally activated by fatty acids and stimulate insulin secretion as well as raise levels of glucagon-like peptide-1 (GLP-1). By increasing insulin secretion and suppressing glucagon, he said, the drug class “may help address several issues that occur in type 2 diabetes that are yet unaddressed.”

Presented at the 71st Scientific Sessions, June, 2011