Core Viewpoint - The successful development of oral semaglutide marks a significant breakthrough in the administration of peptide drugs, overcoming challenges related to stability, absorption, and individual variability in efficacy [4][6][9]. Group 1: Development and Mechanism - Oral semaglutide has successfully addressed multiple barriers, including instability due to gastric acid and digestive enzymes, large molecular size affecting absorption, and individual differences in therapeutic response [4]. - The use of SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) enhances the solubility and absorption of the peptide, while also protecting it from degradation [6]. - Pharmacokinetic and pharmacodynamic studies have established optimal dosing methods, ensuring that the semaglutide tablet combined with 300 mg of SNAC achieves maximum bioavailability [6]. Group 2: Clinical Efficacy - Clinical studies have demonstrated that a 14 mg oral semaglutide tablet can significantly reduce HbA1c levels by approximately 2% and promote weight loss [9]. - In the OASIS 1 study, participants with an average baseline weight of 105.4 kg experienced an average weight reduction of 17.4% (18.34 kg) with the 50 mg oral semaglutide group, indicating a more pronounced weight loss effect compared to previous studies [9]. Group 3: Mechanism of Action - Semaglutide acts as a "satiety manager" by directly suppressing appetite through central nervous system activation, particularly in the hypothalamus and brainstem [10]. - It slows gastric emptying, prolonging the feeling of fullness, and stabilizes blood sugar levels, indirectly reducing appetite fluctuations [11][12]. - The drug activates three key pathways: central nervous system pathways that enhance satiety signals, gastrointestinal-vagal pathways that slow gastric emptying, and pancreatic-metabolic pathways that smooth blood sugar levels [13].