Core Viewpoint - The global obesity crisis is escalating, with the World Health Organization predicting that the number of obese individuals will exceed 1 billion by 2024 and potentially reach 4 billion by 2035. This public health challenge is driving innovation in the development of weight-loss treatments, particularly amylin analogs, which may reshape the market for metabolic disease therapies worth billions of dollars [4]. Group 1: Discovery and Mechanism of Amylin - Amylin was discovered in 1987 by a research team at the University of Auckland, which identified a unique substance in pancreatic tissues of diabetic patients, leading to its naming as Islet Amyloid Polypeptide (IAPP) and later as Amylin. This discovery opened new avenues for understanding and treating metabolic diseases [6]. - Amylin, a neuroendocrine hormone composed of 37 amino acids, works alongside insulin to regulate various metabolic processes, including suppressing glucagon secretion, enhancing insulin sensitivity, and reducing appetite through central nervous system mechanisms. It also delays gastric emptying and promotes energy expenditure, contributing to weight loss [7]. Group 2: Development of Amylin Analog Drugs - The evolution of amylin analogs has progressed from short-acting to long-acting formulations. Pramlintide, the first synthetic amylin analog approved in 2005, faced limitations in clinical use due to side effects and inadequate efficacy, leading to early treatment discontinuation in about half of patients [8]. - Recent advancements include the long-acting amylin analogs, Cagrilintide and the combination product CagriSema, which have shown significant weight loss effects in clinical trials. Cagrilintide demonstrated a dose-dependent weight loss of 6% to 10.8%, outperforming placebo and showing comparable safety profiles to existing treatments [9]. Group 3: Innovations in Delivery Methods - The development of Amycretin, the first GLP-1/amylin dual receptor agonist, represents a breakthrough in drug delivery methods, utilizing an oral administration system that enhances intestinal absorption and bioavailability. Early clinical trials indicated an average weight loss of 13.1% in treated patients, highlighting its potential as a leading candidate in metabolic disease therapy [10]. - The trajectory of amylin analogs from short-acting to long-acting therapies and now to oral formulations illustrates significant progress in the treatment of metabolic diseases, offering patients more effective and convenient treatment options [11].