TAK-875, a GPR40/FFAR1 agonist, in combination with metformin prevents progression of diabetes and β-cell dysfunction in Zucker diabetic fatty rats.

ABSTRACT:

Background and purpose

TAK-875, a selective GPCR40/free fatty acid receptor 1 agonist, improves glycaemic control by increasing glucose-dependent insulin secretion. Metformin is a first-line drug for treatment of type 2 diabetes that improves peripheral insulin resistance. Based on complementary mechanism of action, combining these agents is expected to enhance glycaemic control. Here, we evaluated the chronic effects of TAK-875 monotherapy and combination therapy with metformin in diabetic rats.

Experimental approach

Long-term effects on glycaemic control and β-cell function were evaluated using Zucker diabetic fatty (ZDF) rats, which develop diabetes with hyperlipidaemia and progressive β-cell dysfunction.

Key results

Single doses of TAK-875 (3-10 mg·kg(-1) ) and me

SUBMITTER: Ito R 

PROVIDER: S-EPMC3791995 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature