Cardiovascular and Metabolic Disease, Johnson & Johnson Innovative Medicine Research & Development, Spring House, PA, United States.
Front Endocrinol (Lausanne). 2023 Dec 14;14:1301017. doi: 10.3389/fendo.2023.1301017. eCollection 2023.
G protein-coupled receptors (GPCRs) have emerged as important drug targets for various chronic diseases, including obesity and diabetes. Obesity is a complex chronic disease that requires long term management predisposing to type 2 diabetes, heart disease, and some cancers. The therapeutic landscape for GPCR as targets of anti-obesity medications has undergone significant changes with the approval of semaglutide, the first peptide glucagon like peptide 1 receptor agonist (GLP-1RA) achieving double digit weight loss (≥10%) and cardiovascular benefits. The enhanced weight loss, with the expected beneficial effect on obesity-related complications and reduction of major adverse cardiovascular events (MACE), has propelled the commercial opportunity for the obesity market leading to new players entering the space. Significant progress has been made on approaches targeting GPCRs such as single peptides that simultaneously activate GIP and/or GCGR in addition to GLP1, oral tablet formulation of GLP-1, small molecules nonpeptidic oral GLP1R and fixed-dose combination as well as add-on therapy for patients already treated with a GLP-1 agonist.
G 蛋白偶联受体（GPCR）已成为治疗各种慢性疾病（包括肥胖症和糖尿病）的重要药物靶点。肥胖症是一种复杂的慢性疾病，需要长期管理，易引发 2 型糖尿病、心脏病和某些癌症。随着首个肽类胰高血糖素样肽 1 受体激动剂（GLP-1RA）司美格鲁肽的批准，用于抗肥胖症药物的 GPCR 靶点治疗领域发生了重大变化，该药物可实现两位数的体重减轻（≥10%）和心血管获益。体重减轻效果增强，预计可对肥胖相关并发症产生有益影响，并减少主要不良心血管事件（MACE），这推动了肥胖症市场的商业机会，吸引了新的参与者进入该领域。在针对 GPCR 的方法方面取得了重大进展，例如同时激活 GIP 和/或 GCGR 以及 GLP1 的单一肽、GLP-1 的口服片剂制剂、非肽类口服 GLP1R 小分子和固定剂量联合以及已接受 GLP-1 激动剂治疗的患者的附加治疗。
