273-LB: The Effect of Bispecific GLP-1R/GLP-2R Agonist Compared with Dual GLP-1R/GLP-2R Agonist and Dual GLP-1R/GIPR Agonist in Diet-Induced Obesity Mouse Model

Abstract

Obesity is a global health challenge with few pharmacological options associated with type 2 diabetes and cardiovascular (CV) complications. MG12, a bispecific GLP-1R/GLP-2R Fc-fused agonist, was manufactured to show its potential advantage over current comparable dual incretin agonists. In this study, we observed that MG12 was superior in body weight (BW) reduction when compared to dual GLP-1R/GLP-2R agonist as well as combination therapy of GLP-1R and GLP-2R Fc-fused agonist. We predicted this as the result of the optimized state of increasing GLP-1 activity and the bispecific structural nature. Also, MG12 showed BW reduction in a dose-dependent manner. Interestingly, MG12 at a high dose showed similar BW reduction to dual GLP-1R/GIPR agonist despite a lesser decrease in food intake after the first injection. Additionally, we noted a higher reduction in fat/muscle mass ratio after the last injection in the comparable BW reduced group. Furthermore, MG12 showed a decrease in low grade inflammation biomarkers, which may indicate a potential CV outcome benefit. Therefore, MG12 may be a promising new therapeutic approach for obesity-related metabolic disorders. Disclosure T. Oh: Employee; Progen. Co., Ltd, SL Metagen. Co., Ltd. S. Yang: None. J. Roh: None. J. Sung: None.