PDF(Pubmed)
Abstract：
Guidelines for the management of obesity and type 2 diabetes (T2DM) emphasize the importance of lifestyle changes, including a reduced-calorie diet and increased physical activity. However, for many people, these changes can be difficult to maintain over the long term. Medication options are already available to treat obesity, which can help reduce appetite and/or reduce caloric intake. Incretin-based peptides exert their effect through G-protein-coupled receptors, the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and glucagon peptide hormones are important regulators of insulin secretion and energy metabolism. Understanding the role of intercellular signaling pathways and inflammatory processes is essential for the development of effective pharmacological agents in obesity. GLP-1 receptor agonists have been successfully used, but it is assumed that their effectiveness may be limited by desensitization and downregulation of the target receptor. A growing number of new agents acting on incretin hormones are becoming available for everyday clinical practice, including oral GLP-1 receptor agonists, the dual GLP-1/GIP receptor agonist tirzepatide, and other dual and triple GLP-1/GIP/glucagon receptor agonists, which may show further significant therapeutic potential. This narrative review summarizes the therapeutic effects of different incretin hormones and presents future prospects in the treatment of T2DM and obesity.
摘要：
肥胖和2型糖尿病（T2DM）管理指南强调改变生活方式的重要性，包括减少卡路里的饮食和增加体力活动。然而,对很多人来说,这些变化可能很难长期维持。已经有了治疗肥胖症的药物选择，这可以帮助减少食欲和/或减少热量摄入。基于肠促胰岛素的肽通过G蛋白偶联受体发挥作用，胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）的受体，胰高血糖素肽激素是胰岛素分泌和能量代谢的重要调节因子。了解细胞间信号通路和炎症过程的作用对于开发有效的肥胖症药物至关重要。GLP-1受体激动剂已成功使用,但是据推测，它们的有效性可能受到脱敏和靶受体下调的限制。越来越多的作用于肠促胰岛素激素的新药正被用于日常临床实践，包括口服GLP-1受体激动剂，GLP-1/GIP受体双重激动剂替拉肽，和其他双重和三重GLP-1/GIP/胰高血糖素受体激动剂，这可能显示出进一步显著的治疗潜力。本文综述了不同肠促胰岛素激素的治疗效果，并对未来治疗2型糖尿病和肥胖的前景进行了展望。
