• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

A randomized, double-blind, multicenter study demonstrated that a G-protein-coupled receptor 40 (GPR40) agonist had glucose-lowering efficacy for the treatment of type 2 diabetes. The novel agent significantly reduced HbA1C compared with placebo, with efficacy that was comparable with glimepiride but with a significantly lower rate of hypoglycemia.

Prabhakar Viswanathan, MD, PhD, State University of New York, Buffalo, New York, USA, reported the findings of the study. He first explained that the agent, TAK-875, is a highly selective and potent GPR40 agonist with glucose-dependent insulinotropic action.

The study was designed to evaluate the efficacy, safety, and tolerability of TAK-875 at 5 doses—6.25, 25, 50, 100, and 200 mg—given once daily for 12 weeks. The 426 study subjects were randomly assigned a different dose of TAK-875, glimepiride (4 mg), or placebo, with 60 to 62 subjects in each group. About 75% of the 426 patients were taking metformin at baseline.

The primary efficacy endpoint was change in HbA1C from baseline to Week 12. Several other efficacy and safety endpoints were also evaluated, including changes in HbA1C over time, fasting plasma glucose (FPG) level, 2-hour glucose level during oral glucose tolerance testing (OGTT), and incidence of hypoglycemia.

Dr. Viswanathan reported that all doses of the drug led to greater reductions in HbA1C at 12 weeks than placebo, with the efficacy of the drug reaching a plateau at the 50-mg dose. Doses ≥50 mg of TAK-875 led to reductions that were comparable with those found with glimepiride. The mean reduction in HbA1C was significantly different by the time of the first testing (4 weeks), and the difference remained significant at all time points. Nearly one-third of patients who were treated with TAK-875 had a decrease in HbA1C of 1.5% or more at Week 12, a rate that was comparable with that for the glimepiride group and significantly better than that for the placebo group (p<0.05).

TAK-875 rapidly reduced the FPG, with a substantial difference by Week 1. The mean reduction in the 2-hour glucose level during OGTT was significantly greater with doses of TAK-875 ≥25 mg compared with placebo (p<0.05). β-cell function also appeared to improve, with significantly higher HOMA-β scores for TAK-875 at doses ≥50 mg compared with placebo (p<0.05).

All doses were well tolerated over the course of the study. The incidence of hypoglycemia in all of the TAK-875 groups was similar to that in the placebo group (2.0% vs 3.3%) and was significantly lower than that in the glimepiride group (16.1%; p<0.05).

The rates of treatment-emergent adverse events in the TAK-875 groups ranged from 1.0% (hyperglycemia) to 5.3% (urinary tract infection). The rate of any adverse event was lower for TAK-875 compared with glimepiride (48.7% vs 61.3%).

TAK-875 is the first agent in its class to reach clinical development for the treatment of type 2 diabetes. The drug is being developed as an adjunct therapy to diet and exercise for improving glycemic control in patients with type 2 diabetes.

• © 2011 MD Conference Express