The past few years have seen a rapid increase in the development and use of new drugs to treat obesity, many of which target the incretin system. A new study has reported the phase I results of AMG 133 (also known as maridebart cafraglutide), which is a bispecific molecule consisting of a glucose-dependent insulinotropic peptide receptor (GIPR) antagonist antibody conjugated to two glucagon-like peptide 1 (GLP1) agonists.

The researchers confirmed the activity of AMG 133 in cell models and preclinical animal models. In cell-based functional assays, AMG 133 had GIPR antagonist and GLP1 receptor agonist activity. Treating male obese mice and cynomolgus monkeys with AMG 133 resulted in reduced body weight and improved metabolic parameters, including blood levels of glucose.

过去几年，治疗肥胖症的新药的开发和使用迅速增加，其中许多药物针对肠促胰岛素系统。一项新研究报告了 AMG 133（也称为 maridebart cafraglutide）的 I 期结果，该药物是一种双特异性分子，由与两个胰高血糖素样肽 1 (GLP1) 缀合的葡萄糖依赖性促胰岛素肽受体 (GIPR) 拮抗剂抗体组成激动剂。

研究人员在细胞模型和临床前动物模型中证实了 AMG 133 的活性。在基于细胞的功能测定中，AMG 133 具有 GIPR 拮抗剂和 GLP1 受体激动剂活性。用 AMG 133 治疗雄性肥胖小鼠和食蟹猴可减轻体重并改善代谢参数，包括血糖水平。