ScholarWorks@중앙대학교

초록

GPR119 is a promising therapeutic target for type 2 diabetes because of its role in enhancing glucose-stimulated insulin secretion and GLP-1 release. We investigated the anti-diabetic and anti-obesity effects of HG043, a novel and potent thienopyrimidine-based GPR119 agonist, by comparing its pharmacological activities to those of MBX-2982 (a known GPR119 agonist) and sibutramine (an appetite suppressant) in both in vitro and in vivo models. HG043 exhibited potent agonistic activity for human GPR119 and demonstrated enhanced efficacy compared to MBX-2982 in stimulating incretin secretion in pancreatic β-cell lines. Single and long-term treatment with HG043 resulted in significant improvements in diabetic and obesity parameters compared to both MBX-2982 and sibutramine in both healthy and disease models. Furthermore, HG043 demonstrated synergistic glucose-lowering effects when combined with metformin or sitagliptin. These findings suggest that HG043 may serve as a promising therapeutic option for the treatment of type 2 diabetes with obesity patients.

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