1394371-71-1

Chronic antihyperglycemic efficacy of MK8722 (MK-8722) is evaluated in db/db mice, a leptin receptor-deficient T2DM model. Once-daily administration of MK8722 results in dose-dependent lowering of ambient blood glucose. On treatment day 12, glucose reductions after MK8722 treatment (30 mpk/day) are comparable to those observed with the PPARγ agonist BRL49653 (3 mpk/day). Unlike BRL49653, the glucose-lowering action of MK8722 manifests without significant effects on body weight, which is a consistent finding. Dose-dependent increases in tissue pACC are maintained throughout the dosing period. Chronic efficacy, without tachyphylaxis, is also observed in additional dysmetabolic and diabetic rodent models. In all cases, efficacy is associated with trough MK8722 plasma levels comparable to the concentrations required to acutely stimulate skeletal muscle glucose uptake. Chronic MK8722 dosing in mice also increases muscle Glut4 protein levels, possibly contributing to efficacy^[1].