A novel GPR40 Agonist (TAK-875) in Subjects with T2 DM

A Randomised, Double Blind, Placebo and Active Controlled, Dose Ranging Study to Determine the Efficacy and Safety of the Novel GPR40 Agonist TAK-875 in Subjects with T2 DM
Prabakar Viswanathan
ADA 2011.

TAK-875 is a potent agonist of GPR40. It has a glucose dependent insulinotropic mechanism. GPR40 in pancreatic cells is coupled with the GQ couplet in the beta cell and modulates signaling within the beta cell.
Of the 426 subjects randomized nearly 90% completed the study. In the TAK-875 group there was equivalence in HbA1c lowering from midway up the dose range when compared with glimepiride 4mg. There was a rapid decline in FBG after initiating treatment and within 4 weeks a significant fall in HbA1c. The fall in HbA1c was equivalent to that seen with glimepiride. By week 12 there was a significant fall in 2-hour BG after an oGTT.
HOMA-b showed similar changes when compared with baseline in the TAK-875 arms and these changes compared with glimepiride. There was no change in body weight in the TAK arms whereas there was a rise in weight in the glimepiride group.
Over the 3 months of the study all doss of TAK-875 there were no significant problems with tolerance.