毒液中的意外发现：减肥“神药”司美格鲁肽的诞生

Core Viewpoint - The article discusses the evolution and advancements in GLP-1 (Glucagon-like peptide-1) drugs, highlighting their development from animal-derived to human-derived, and from short-acting to long-acting formulations, emphasizing their effectiveness in weight loss and diabetes management [4][5][25]. Group 1: Discovery and Development of GLP-1 - The discovery of gut hormones that stimulate insulin secretion dates back to 1932, with the identification of GLP-1 as a significant gut incretin that effectively stimulates insulin secretion at very low concentrations [5][7]. - The first GLP-1 receptor agonist (GLP-1RA), Exendin-4, was derived from the saliva of the Gila monster in 1992, leading to the approval of the first GLP-1RA, Exenatide, in 2005 [8]. - Clinical studies showed that patients treated with Exenatide experienced an average weight loss of 2.49 kg, with 30% of patients losing over 5% of their body weight [8]. Group 2: Advancements in Long-Acting GLP-1RA - The natural half-life of GLP-1 is very short (1-2 minutes), prompting the development of drugs that inhibit DPP-4 to extend GLP-1's action [9]. - Liraglutide was launched in 2009, allowing for once-daily injections due to its significantly extended half-life [12]. - In 2017, Semaglutide was introduced, showing remarkable weight loss results, with obese patients losing an average of 15% of their body weight [13]. Group 3: New Generation GLP-1RA and Market Dynamics - Tirzepatide, launched in 2022, is the first drug to target both GLP-1R and GIPR, demonstrating superior weight loss effects compared to Semaglutide, with patients losing between 16% to 22.5% of their body weight [15]. - The patent expiration of several GLP-1RA drugs, including Liraglutide in China and Semaglutide in 2026, is expected to intensify competition in the diabetes treatment market [17]. - The ongoing research on Retatrutide shows promising results, with a 24.2% weight loss in patients after 48 weeks of treatment, setting a new record in weight loss medications [17].