In type 2 diabetes mellitus (T2DM) patients, thegradual loss of pancreatic b-cell function is a characteristicfeature of disease progression that is associated with sustainedhyperglycemia. Recently, G protein-coupled receptor119 (GPR119) has been identified as a promising anti-diabetictherapeutic target. It is predominantly expressed inpancreatic b-cells, directly promotes glucose stimulatedinsulin secretion and indirectly increases glucagon-like peptide1 (GLP-1) levels reducing appetite and food intake. Activation of GPR119 leads to insulin release in b-cells byincreasing intracellular cAMP. Here, we identified a novelstructural class of small-molecule GPR119 agonists,HD0471042, consisting of substituted a 3-isopropyl-1,2,4-oxadiazol-piperidine derivative with promising potential forthe treatment of T2DM. The GPR119 agonist, HD0471042increased intracellular cAMP levels in stably human GPR119 expressing CHO cell lines and HIT-T15 cell lines, hamster bcellline expressing endogenously GPR119. HD0471042,significantly elevated insulin release in INS-1 cells of ratpancreatic b-cell line. In in vivo experiments, a single dose ofHD0471042 improved glucose tolerance. Insulin and GLP-1level were increased in a dose-dependent manner. Treatmentwith HD0471042 for 6 weeks in diet induced obesity miceand for 4 weeks in ob/ob and db/db mice improved glycemiccontrol and also reduced weight gain in a dose-dependentmanner. These data demonstrate that the novel GPR119agonist, HD0471042, not only effectively controlled glucoselevels, but also had an anti-obesity effect, a feature observedwith GLP-1. We therefore suggest that HD0471042 representsa new type of anti-diabetes agent with anti-obesitypotential for the effective treatment of type 2 diabetes.