What is GLP-1?

In diabetes, obesity, fatty liver three metabolic diseases of the new drug research and development track, GLP-1 series polypeptide is the current market demand for the highest active polypeptide raw materials, but also the major synthetic polypeptide factory standing catalog peptide and custom synthesis core category. The full name of the GLP-1 is glucagon-like peptide -1, which is an endogenous active polypeptide naturally secreted by human small intestinal L cells. It is the core signal molecule of the body to regulate postprandial blood sugar, fat metabolism and appetite. The natural active GLP-1 secreted by the human intestine mainly contains two mature fragments: GLP-1(7-37) and GLP-1(7-36)NH₂. After eating, the intestinal nutrition stimulation will release a large number of these two peptides, through multiple ways to smooth postprandial blood sugar, inhibit excess fat accumulation. However, natural GLP-1 have fatal clinical defects: DPP-4 dipeptidyl peptidase is widely present in human body, which will rapidly shear and degrade the active GLP-1 within 2 minutes, resulting in the half-life of natural polypeptide in vivo being less than 2 minutes, the drug effect is fleeting after intravenous infusion, and it cannot be directly used as an injection drug for long-term use. In order to solve the pain points of short half-life and frequent administration of natural polypeptides, global pharmaceutical companies and peptide synthesis companies have developed a series of long-acting GLP-1 receptor agonist polypeptide APIs through chemical engineering technologies such as amino acid substitution, fatty acid side chain coupling, peptide chain modification, and fusion proteins. According to the structure, drug delivery cycle and length of action, the industry is divided into three categories. The first category is short-acting GLP polypeptides, representing raw materials: exenatide, lisisenatide. This kind of polypeptide is not modified by long chain fatty acid, and needs multiple injections every day. It is mostly used for early mechanism research and short-term animal model experiments, and belongs to conventional spot catalog peptides. The second category is single-target long-acting GLP-1  polypeptides, which are also the most mature category currently commercialized, representing: liraglutide, semaglutide, and dulaglutide. Liraglutide and semaglutide are connected to C16/C18 fatty acid side chains and combined with plasma albumin to prolong the residence time in the body, thus realizing daily/weekly administration. At the same time, they are approved for two major indications of hypoglycemic and weight loss. The supporting bulk drugs are divided into two specifications of scientific research grade and pharmaceutical grade API, and are GLP polypeptides with the largest purchase volume. The third category is the multi-target co-agonist polypeptides that have exploded in recent years, including GLP-1/GIP double-agonist, GLP-1/GCG double-agonist and GLP-1/GIP/GCG triple-agonist, representing the raw materials of telpotide, codutide, Pemvidutide and SAR441255 ternary polypeptides. This kind of polypeptide can activate two or more metabolic pathways at the same time, and is better than single-target GLP for fatty liver and severe obesity. It is also the core customized polypeptide raw material in the clinical stage of innovative pharmaceutical enterprises. Many customers will wonder: since GLP-1 polypeptide can improve fatty liver, can it directly act on liver cells? At present, a large number of immunohistochemistry and single-cell sequencing experiments have confirmed that human liver cells, hepatic stellate cells and Kupffer cells, the three types of liver core functional cells, do not express classical GLP-1 receptors at all. GLP-1 there is no direct hepatoprotective target, all lipid-lowering, anti-inflammatory, anti-fibrosis effects all rely on the indirect regulation of extrahepatic tissue, which is also the core of the entire GLP liver disease research and development field of the underlying theory, all cell experiments, animal modeling, clinical trials are carried out around this mechanism.