口服，将决定GLP-1药物能否从“明星药物”升级为“普及性重磅药物”的关键

Core Viewpoint - The article emphasizes the growing recognition and effectiveness of GLP-1 receptor agonists in managing obesity and type 2 diabetes, highlighting the transition from injectable to oral formulations as a key development for broader accessibility and patient adherence [4][12]. Injectable GLP-1 Agonists - Semaglutide can lead to a weight loss of approximately 10%-15% and a reduction in HbA₁c by about 1.5%-2.0%, along with improvements in cardiovascular events and liver fat [4]. - Tirzepatide, as a dual agonist of GLP-1 and GIP, shows superior efficacy and has been validated in clinical settings, marking a significant milestone in metabolic treatment [4]. Oral Semaglutide - Oral semaglutide (Rybelsus) is the first GLP-1 oral medication, with PIONEER studies showing an average HbA₁c reduction of 1.0%-1.5% and a weight loss of about 4 kg over 52 weeks, with good overall tolerability [6]. - PIONEER-12's subgroup analysis in Chinese populations demonstrated statistically significant advantages in controlling HbA₁c and weight compared to sitagliptin, with no new safety signals identified [8]. Small Molecule Oral GLP-1 - Eli Lilly's small molecule GLP-1 agonist Orforglipron shows better oral stability and production advantages, with Phase 3 data indicating an average weight loss of 7.3 kg and HbA₁c reduction of about 1.5% over 40 weeks [10]. - In the ATTAIN-2 study, high-dose groups achieved a weight loss of 10.5% (approximately 10.4 kg) and over 75% of patients met diabetes remission criteria, indicating comparable efficacy to injectable GLP-1 products [10]. Market Potential and Accessibility - The transition to oral GLP-1 medications is seen as a key factor in making these treatments more accessible, with advantages in cost, adherence, and safety compared to injectable forms [12][13]. - The article suggests that the future will involve a combination of injectable and oral forms tailored to individual patient needs, enhancing metabolic management [12]. Future Outlook - The anticipated approval of oral Wegovy (oral semaglutide) for chronic weight management could mark a significant milestone as the first oral GLP-1 for weight loss [11]. - The article predicts a "new era" for oral GLP-1 medications in China, driven by clinical advancements, policy clarity, and improved insurance coverage, which will enhance the management of metabolic diseases [14].