GLP-1 belongs to the incretin family. Its secretion is regulated by feeding activities and has a blood glucose concentration-dependent hypoglycemic effect. GLP-1 receptor agonist (GLP-1RA) can simulate the physiological effect of GLP-1 and prolong the action time. GLP-1 and glucose-dependent insulin stimulating polypeptide (GIP) are the two main types of incretin, of which the former is significantly reduced in type 2 diabetes mellitus (even in people with impaired glucose tolerance) and thus becomes an important therapeutic target. Studies on the physiological effects of GLP-1 have shown that it can not only enhance the beta cell response, but also reduce the glucagon secretion by acting on alpha cells, thereby reducing the liver sugar output, and act on the feeding center and the stomach, inhibit appetite and slow down gastric emptying, thereby reducing the beta cell load. Glucagon-like peptide-1 (GLP-1) receptor agonists, as a new type of hypoglycemic drug, can effectively reduce body weight and improve metabolic disorders while lowering blood glucose, but the mechanism of weight loss has not been fully clarified. It was previously thought that the effect of GLP-1 receptor agonists on reducing body weight was mainly related to its inhibition of central appetite and delay of gastric emptying. Glucagon-likepeptide includes glucagon-like peptide-1 (GLP-1) and Glucagon-like peptide-2 (GLP-2), both of which are derived from Proglucagon [1-3]. Glucagon-likepeptide consists of 158 amino acids. Can be cut into different peptide chains Chemicalbook, as shown below. Because GLP-1 has the pharmacological effects of promoting insulin secretion [4], protecting islet beta cells, inhibiting glucagon secretion, inhibiting gastric emptying [5], and reducing appetite, it can be clinically used in the treatment of type 2 diabetes and obesity. GLP-2 is a nutritional factor, which has the pharmacological effects of promoting small intestine growth, inhibiting apoptosis, promoting gastric emptying and increasing appetite, and can be used clinically to treat short bowel syndrome. GLP-1 with biological activity in human body is mainly GLP-1(7-36) amide and GLP-1(7-37). Natural GLP-1 is easily hydrolyzed and deactivated by dipeptidyl peptidase Ⅳ(DPP-Ⅳ) rapidly (half-life less than 5min) [5], which has no clinical use value and can modify GLP-1 structure. Masking the binding site of DPP-Ⅳ and prolonging the half-life of DPP-ⅳ are the main research topics in the development of DPP-ⅳ. There are already a number of GLP-1 drugs on the market, and this class of drugs will be a new growth point for diabetes drugs in the next 10 years. Currently, five GLP-1 agonists have been approved by the CFDA, including Bestida (Exenatide), Bestian (Exenatide microspheres), Novo Nordisk's Novo Lirol (Liraglutide), Sanofi's Risemin (Lirisnatide), and Shanghai Renhui Biological's Yisentai (Benalutide). Dulaglutide, Semaglutide, and Albiglutide are in clinical trials.
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