Unit of Internal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Geriatric Unit, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Front Endocrinol (Lausanne). 2023 Feb 22;14:1095753. doi: 10.3389/fendo.2023.1095753. eCollection 2023.
The occurrence of obesity is an increasing issue worldwide, especially in industrialized countries. Weight loss is important both to treat obesity and to prevent the development of complications. Currently, several drugs are used to treat obesity, but their efficacy is modest. Thus, new anti-obesity treatments are needed. Recently, there has been increased interest in the development of incretins that combine body-weight-lowering and glucose-lowering effects. Therefore, a new drug that simultaneously coactivates both the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R) has been developed. Tirzepatide, the first in this class, improves glycemic control by increasing insulin sensitivity and lipid metabolism as well as by reducing body weight. Combining the activation of the two receptors, greater improvement of β-cell function offers more effective treatment of diabetes and obesity with fewer adverse effects than selective GLP-1R agonists. In the present review, we discuss the progress in the use of GIPR and GLP-1R coagonists and review literature from studies, animal studies, and human trials, highlighting the synergistic mechanisms of tirzepatide.
肥胖的发生是一个全球性的日益严重的问题，尤其是在工业化国家。减肥对于治疗肥胖症和预防并发症的发生都很重要。目前，有几种药物可用于治疗肥胖症，但疗效有限。因此，需要新的抗肥胖症治疗方法。最近，人们对开发能够同时降低体重和降低血糖的肠促胰岛素的兴趣有所增加。因此，开发了一种同时激活葡萄糖依赖性胰岛素释放多肽 (GIP) 受体 (GIPR) 和胰高血糖素样肽-1 受体 (GLP-1R) 的新型药物。作为该类药物中的第一种，替西帕肽通过提高胰岛素敏感性和脂质代谢以及减轻体重来改善血糖控制。两种受体的联合激活，可改善β细胞功能，与选择性 GLP-1R 激动剂相比，可更有效地治疗糖尿病和肥胖症，且不良反应更少。在本综述中，我们讨论了 GIPR 和 GLP-1R 共激动剂的应用进展，并回顾了来自研究、动物研究和人体试验的文献，强调了替西帕肽的协同作用机制。
