At present, there are a variety of short-acting (exenatide, liraglutide, etc.) and long-acting (albiglutide, dulaglutide, semaglutide, etc.) GLP-1RA drugs on the market in the world. The disease is adult type 2 diabetes, and there are only two approved weight loss indications, liraglutide and semaglutide.

GLP-1R has become a popular target for weight loss based on phase 3 clinical trials of liraglutide and semaglutide in obese people without diabetes. GLP-1 receptor agonists have shown good weight loss effects, compared with The placebo two drugs reduced patients' body weight by 5.4% and 12.5%, respectively. And after showing good safety, most of the adverse reactions of GLP-1RA are gastrointestinal reactions (such as nausea, constipation, etc.), which are usually mild and mostly occur in the early stage of medication. ease.

Liraglutide (Saxenda) became the first GLP-1-based weight loss drug to be introduced to the U.S. market in 2014 for the treatment of obesity in adults, and was approved in 2020 for weight management in obese adolescents 12 years and older. Liraglutide is modified from natural GLP-1 and needs to be administered once a day. In response to the problem that natural GLP-1 is easily degraded by enzymes in vivo, Novo Nordisk replaced the 27-position lysine (Lys) residue of GLP-1 with arginine (Arg), and modified the peptide chain by ten The six-carbon fatty acid side chain (C16) makes the modified polypeptide have high chemical stability and is not easy to be degraded by dipeptidyl peptidase-4 (DPP4), so the in vivo half-life of liraglutide is longer, reaching 12-14 hours, only one subcutaneous injection per day is required.

In 2021, the FDA approved 2.4 mg of semaglutide (Wegovy) for chronic disease management in adults who are obese or overweight and have at least one weight-related disorder such as high blood pressure or cholesterol or type 2 diabetes. Semaglutide is modified on the basis of liraglutide, and the alanine residue (Ala) at position 8 of liraglutide is replaced by the rare amino acid α-aminobutyric acid (Aib), which can resist enzymes The cleavage of liraglutide, which replaces the 16-carbon fatty acid side chain (C16) of liraglutide with the 18-carbon fatty acid side chain (C18) with one free carboxyl group, improves the affinity for GLP-1R and plasma protein binding , greatly prolongs the half-life of the drug, and only needs to be injected subcutaneously once a week.

Liraglutide, one of the core varieties of Novo Nordisk's metabolic sector, has grown rapidly after Saxenda was approved for the treatment of overweight/obesity in adults in 2014, with sales reaching US$850 million in 2019. After semaglutide Wegovy is approved for obesity indications in 2021, Novo Nordisk will merge the weight loss sector into statistics. In 2021, the total sales of the weight loss sector (Saxenda and Wegovy) will be close to 8 billion yuan, a year-on-year increase of 49.8%. In the first half of the year, sales exceeded 6 billion yuan, a year-on-year increase of 98.8%.