Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, PR, China.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University , Nanjing, PR, China.
Expert Opin Ther Pat. 2020 Oct;30(10):781-794. doi: 10.1080/13543776.2020.1811851. Epub 2020 Sep 11.
Glucagon-like peptide-1 (GLP-1) is an endogenous peptide which is secreted by enteroendocrine L cells, GLP-1 receptor agonists (GLP-1 RAs) can exhibit glucoregulation by stimulating insulin release, promote satiety, delay gastric emptying, and reduce energy intake. Liraglutide is the only GLP-1 RA approved for the treatment of obesity. The phase III clinical study of semaglutide has completed and the result showed significant weight loss effect. GLP-1 RAs have been proven to be safe and effective in clinical trials, they are considered to be promising anti-obesity drugs.
This review provides an overview of recently published patents describing modified GLP-1 RAs, multi-agonists in the treatment or prevention of obesity from January 2015 to April 2020. Moreover, small molecule GLP-1 RAs, recombinant fusion proteins, combination of GLP-1 RAs with other drugs and the preparation of GLP-1 RAs are also covered.
Currently, research on anti-obesity effect of modified GLP-1 RAs has grown significantly, liraglutide accounts for approximately 56% of the global obesity drug market. Long-acting analogues and multifunctional peptides showed good weight loss activity. As more and more clinical trials are carried out, we believe that GLP-1 RAs will occupy an important position in the market of obesity treatment.
胰高血糖素样肽-1（GLP-1）是一种内源性肽，由肠内分泌 L 细胞分泌。GLP-1 受体激动剂（GLP-1RAs）通过刺激胰岛素释放来发挥血糖调节作用，促进饱腹感，延缓胃排空，并减少能量摄入。利拉鲁肽是唯一获批用于治疗肥胖症的 GLP-1RA。司美格鲁肽的 III 期临床试验已经完成，结果显示出显著的减肥效果。GLP-1RAs 在临床试验中已被证明是安全有效的，它们被认为是有前途的抗肥胖药物。
本文综述了 2015 年 1 月至 2020 年 4 月期间发表的描述修饰后的 GLP-1RAs、治疗或预防肥胖的多激动剂的最新专利。此外，还涵盖了小分子 GLP-1RAs、重组融合蛋白、GLP-1RAs 与其他药物的联合应用以及 GLP-1RAs 的制备。
目前，修饰后的 GLP-1RAs 的抗肥胖作用的研究显著增加，利拉鲁肽约占全球肥胖症药物市场的 56%。长效类似物和多功能肽显示出良好的减肥活性。随着越来越多的临床试验的开展，我们相信 GLP-1RAs 将在肥胖症治疗市场中占据重要地位。
