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01-03-2012 | Diabetes | Article

Novel FFAR1 agonist reduces HbA1c without increasing hypoglycemia risk

Abstract

Free abstract

MedWire News: Treatment with the investigational diabetes therapy TAK-875 significantly improves patients' glycemic control without increasing their risk for hypoglycemia, shows a phase II trial published in The Lancet.

Between 33% and 48% of patients who took the drug reached the American Diabetes Association (ADA) glycated hemoglobin (HbA1c) target of less than 7% after 12 weeks of treatment, while being no more likely than patients on placebo to suffer hypoglycemic events, report Charles Burant (University of Michigan Medical School, Ann Arbor, USA) and team.

"In view of the frequent occurrence of hypoglycemia after treatment with sulfonylureas, the low risk of hypoglycemia after treatment with TAK-875 suggests a therapeutic advantage of targeting FFAR1 [free fatty acid receptor 1]," say the authors.

TAK-875 is an agonist of FFAR1 expressed on pancreatic β-cells. Activation of FFAR1 results in increased insulin secretion but only in the presence of rising glucose concentrations, explain the researchers.

"Because increase in insulin secretion by FFAR1 agonists in these studies is glucose-dependent, drugs targeting the FFAR1 receptor could improve glycemic control without the concurrent risk of hypoglycemia," they write.

The team compared the efficacy and safety of TAK-875 with that of placebo and the sulfonylurea glimepiride in 384 diabetes patients who had failed to achieve glycemic control with diet or metformin treatment.

The patients were randomly assigned to receive TAK-875 (6.25, 25, 50, 100, or 200 mg), glimepiride (4 mg), or placebo for a 12-week period, after which they were assessed for changes in HbA1c from baseline.

The researchers report that, at 12 weeks, significant reductions in the mean HbA1c levels were observed in the TAK-875 group, ranging from a mean of 0.65% with the 6.25-mg dose to 1.12% with the 50-mg dose. The latter was similar to the mean HbA1c reduction achieved with glimepiride, of 1.05%. By contrast, the mean decrease in HbA1c from baseline with placebo was only 0.13%.

At weeks 4, 8, and 12, significant dose-dependent reductions in HbA1c occurred in the TAK-875 25-200 mg groups, compared with placebo.

The authors note that the proportion of patients experiencing treatment-emergent hypoglycemic events during the study were similar in the TAK-875 and placebo groups, at 2% and 3%, respectively, whereas a significantly higher rate, of 19%, was reported in the glimepiride group.

"The apparent glucose-dependent increase in insulin secretion reduces the incidence of hypoglycemia compared with the sulfonylurea glimepiride, with minimum side effects," say Burant et al.

"Studies of longer duration are needed to further explore the efficacy and safety of this mechanism of action," they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Sally Robertson