Gpr119 is a G-protein coupled receptor belonging to class A [3]. It is mainly expressed in pancreatic β-cells, intestinal L cells, and some enteroendocrine cells [1,3,4,5]. Gpr119 plays a crucial role in glucose homeostasis by regulating physiological mechanisms such as enhancing levels of glucose-like peptide-1, gastrointestinal incretin hormone, pancreatic beta cell-dependent insulin secretion, and glucose-dependent insulinotropic peptide (GIP) [1]. Activation of Gpr119 can stimulate the secretion of glucagon-like peptide-1 (GLP-1) in the intestinal tract and glucose-dependent release of insulin in pancreatic β-cells [3]. It has thus emerged as a promising target for treating type 2 diabetes mellitus (T2D) without causing hypoglycaemia [6].

In pre-clinical studies, Gpr119 agonists in vitro and in vivo have the potential to regulate incretin hormone release from the gut, followed by pancreatic insulin release, which can regulate blood glucose concentrations [2]. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity did not translate to early-stage clinical trials in T2D patients [2]. Some GPR119 agonist clinical candidates have been discontinued in Phase І or Phase II [3]. New trials on GPR119 agonists are needed, and the future of GPR119 agonists may lie in the development of combination therapy with other T2D therapeutics [2].

In conclusion, Gpr119 is a key regulator of glucose homeostasis, making it an attractive target for T2D treatment. Although pre-clinical studies in rodent models showed promise in controlling glucose levels, translating these findings to human clinical trials has been challenging. Further research, potentially through gene knockout (KO) or conditional knockout (CKO) mouse models, may help better understand Gpr119's function and develop more effective therapeutic strategies for T2D [2].