68周减重18.34 kg，司美格鲁肽片为何能突破多肽药物的口服易降解、难吸收？

Core Viewpoint - The successful development and market launch of oral semaglutide, a GLP-1 receptor agonist, represents a significant breakthrough in overcoming the challenges associated with oral administration of peptide drugs, enhancing patient compliance and treatment options [5][9]. Group 1: Development and Mechanism - Oral semaglutide has overcome multiple barriers, including instability due to gastric acid and digestive enzymes, large molecular size affecting absorption, and individual variability in efficacy [5][7]. - The use of SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) has been pivotal in enhancing the solubility and absorption of semaglutide, while also protecting it from degradation [7][9]. - Pharmacokinetic and pharmacodynamic studies have established optimal dosing methods, ensuring that the semaglutide tablet combined with 300 mg of SNAC achieves maximum bioavailability [7][9]. Group 2: Clinical Efficacy - Clinical studies have demonstrated that a 14 mg dose of oral semaglutide can significantly reduce HbA1c levels by approximately 2% and promote weight loss [9]. - In the OASIS 1 study, participants with obesity or overweight conditions experienced an average weight reduction of 17.4% (18.34 kg) with a 50 mg dose of oral semaglutide, 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 pathways, slowing gastric emptying, and stabilizing blood sugar levels, which collectively reduce food intake [10][12]. - The drug activates GLP-1 receptors in the hypothalamus and brainstem, enhancing satiety signals while inhibiting hunger signals [10][13]. - It also smooths blood sugar fluctuations by promoting insulin secretion and suppressing glucagon release, thereby reducing cravings for high-calorie foods [12][13].