New drug targets have been under research in order to explore
alternative drugs to promote insulin secretion in patients with type-2 diabetes
mellitus. One of the most researched targets amongst these is the G-protein
coupled receptor-40 (GPCR-40) or free-fatty acid receptor-1 (FFAR1). GPCR-40 or
the FFAR1 is found in the pancreatic β-cells,
which secrete insulin.
The FFAR1 receptors are activated by short and long-chain free fatty
acids. Thus, they are activated when the free fatty acid levels in the blood
are high, for example, after a meal. The activation results in insulin secretion.
The FFAR1 receptors have been explored as a target for the treatment of
A phase-2 clinical trial was recently completed which assessed the
potential of TAK-875 in achieving control of blood glucose levels without
causing hypoglycemia or low sugar levels TAK-875 brings about its action by the
activation of FFAR1 receptors.
Four hundred and twenty six patients with type-2 diabetes mellitus were
included in this study. These were patients who did not respond to diet or
metformin. The patients were divided randomly into three study groups: the
first group which received TAK-875, the second group received glimepiride 4 mg
once daily and the third group received placebo for over a period of twelve
The achievement of glycaemic control was measured using the gylcosylated
haemoglobin percentage (HbA1c) from the baseline till the end of the study.
A significant reduction in HbA1c was observed by the researchers in the
group receiving TAK-875.
The researchers also observed that hypoglycemic events were reported to
be higher in the group receiving glimepiride as compared to placebo or TAK-875.
researchers thus concluded that activation of FFAR1 is a viable therapeutic
target for the treatment of type 2 diabetes mellitus.