Core Viewpoint - Pfizer's PF'3944, a monthly injectable GLP-1 receptor agonist, shows promising weight loss results in its Phase IIb clinical trial, validating the company's $10 billion investment in the Metsera drug [4]. Group 1: Clinical Trial Results - In the Vesper-3 trial, approximately 250 overweight or obese adults without type 2 diabetes were randomly assigned to receive one of four dosing regimens of PF'3944 or a placebo [4]. - At week 28, the placebo-adjusted weight loss for the low and medium dose monthly maintenance regimens of PF'3944 was reported at 10% and 12.3%, respectively [4]. - Patients maintained stable weight loss after switching to monthly dosing, with no plateau observed at week 28, indicating potential for continued weight loss in the following weeks [4]. Group 2: Analyst Insights - BMO Capital Markets analysts expressed cautious optimism regarding the data, noting that a 12.3% weight loss at week 28 appears competitive, especially in combination studies with Pfizer's other projects [6]. - The monthly dosing data aligns with competitor performance, suggesting PF'3944 can provide competitive weight loss effects while avoiding the inconvenience of weekly injections [6]. - Pfizer plans to explore higher doses in its Phase III trials, with expectations that placebo-adjusted weight loss could reach around 16% based on high-dose predictions [6]. Group 3: Safety and Future Plans - Pfizer has not yet released complete safety data for week 28, but existing gastrointestinal adverse event data indicates that most side effects were mild to moderate, with few severe cases of nausea or vomiting [8]. - In the low and medium dose groups, 10 patients discontinued treatment due to adverse events, while no patients in the placebo group stopped treatment for this reason [8]. - Pfizer is initiating Phase III trials for PF'3944 with weekly dosing and plans to start an additional nine Phase III studies this year, focusing on both diabetic and non-diabetic patients, as well as evaluating monthly dosing regimens [8].

Core Viewpoint - Semaglutide, a GLP-1 receptor agonist, effectively aids in weight loss by enhancing insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and increasing satiety, leading to reduced appetite and food intake [4][6]. Mechanism of Action - Semaglutide activates specific neurons in the hypothalamus, signaling a feeling of fullness before eating, which is particularly effective in treating obesity [5]. - The appetite-reducing effects of semaglutide occur through three main mechanisms: - Central action: It acts on the hypothalamus to reduce appetite and hunger [6]. - Gastrointestinal action: It slows gastric emptying, increasing feelings of fullness [6]. - Altered food preferences: Patients show a significant decrease in preference and intake of high-fat, fried, or sweet foods [6]. Clinical Efficacy - In clinical trials, patients using semaglutide for 68 weeks lost an average of 15.3 kg, compared to 2.6 kg in the placebo group, with a weight reduction rate of 14.9% versus 2.4% [4]. - The approval of semaglutide for weight management in China is expected to provide a breakthrough solution for overweight and obese patients, enhancing access to effective treatment [13]. Regulatory Approvals - In January 2024, oral semaglutide (Rybelsus) was approved in China for treating type 2 diabetes, marking the first oral GLP-1 receptor agonist approved in the country [9]. - On June 25, 2024, the NMPA approved Wegovy, a semaglutide injection for long-term weight management in China [11]. - The approval of oral semaglutide in the U.S. in December 2025 for weight management and cardiovascular risk reduction signifies a new phase in weight loss medication competition [15][16]. Clinical Trial Data - The OASIS clinical trial demonstrated that daily administration of 25 mg oral semaglutide resulted in an average weight loss of 16.6% over 64 weeks, comparable to the 2.4 mg weekly injection [17]. - Approximately one-third of participants achieved a weight loss of 20% or more, addressing previous concerns about the efficacy of oral GLP-1 treatments [17].

Core Viewpoint - The article discusses the turnaround of Hanyu Pharmaceutical, which is expected to achieve a net profit of 40 to 50 million yuan in 2025, marking its first return to profitability in three years, driven by the growth of GLP-1 raw materials and CRDMO business [5][6]. Financial Performance - Hanyu Pharmaceutical's revenue is projected to reach 950 to 980 million yuan in 2025, a significant increase from 590 million yuan in 2024, indicating a stepwise improvement rather than a one-time recovery [6]. - The company has signed a 180 million yuan sales contract for GLP-1 raw materials, which is expected to significantly enhance its profit structure [7][8]. Market Dynamics - The GLP-1 raw material market is becoming increasingly competitive, with major players like CordenPharma investing over 900 million euros in expanding their production capacity in the U.S. and Europe [8]. - Domestic competitors such as Nuotai Bio and Shengnuo Bio are also ramping up production, leading to a shift in customer selection criteria from availability to stability, cost-effectiveness, and reliability [8]. Future Outlook - While the increase in GLP-1 raw material production has pushed Hanyu Pharmaceutical into profitability, the sustainability of orders and pricing will be tested as competition intensifies [9]. - The recent performance signals improvements in cash flow and order fulfillment, but the company must maintain its position in a rapidly crowded market [9].

整理 | GLP1减重宝典内容团队 但仔细看看身边的人，你会发现几乎没有例外。只要开始长期上班，只要工作节奏一旦固定，体重就像被悄悄推着往前走。 为什么偏偏是工作三年左右最容易胖？答案其实很简单。前两年，大多数人还在硬撑。撑状态、撑精力、撑形象，觉得再累也要咬牙扛住。但 到第三年，你大概已经明白，这不是一个短跑，而是一场没那么容易停下来的长跑。于是很多事开始慢慢松掉。运动变成下周再说，吃饭变成 能填饱就行，熬夜从偶尔变成常态。身体并不会立刻反抗，它只是把账记下来，等你有一天站上体重秤，一次性给你看结果。 更扎心的是，越认真工作的人，反而越容易胖。不是因为吃得好，而是因为吃得太随意。边回消息边吃饭，边开会边扒两口，饭在嘴里，大脑 却在别的地方。等你停下来，已经完全不记得刚才吃了多少，只觉得好像没吃饱，于是顺手再来点。你以为是食欲问题，其实是注意力被工作 掏空了。 久坐当然是原因，但它真的不是最关键的那个。真正推着体重往上走的，是长期的压力、被压缩的睡眠，还有越来越乱的饮食节奏。压力大 了，人就更容易想吃点让自己好受的东西。睡不够的时候，身体会自动降低代谢效率，顺便多存点能量。不规律的进食更不用说了，不吃早 饭， ...

以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 味觉系统作为调节摄食行为的首要"感知门户"，通过舌部和腭上皮的特化味觉受体细胞(TRC)识别味道信号，经五级突触传导将信息送达味觉 皮层。研究者此前已成功鉴定出负责感知甜、苦、鲜、咸、酸五种基本味觉的TRC，证实每种味觉均由表达特定受体的细胞群专门负责。 蔗糖约1万年前首次在新几内亚被人类提取利用，11世纪以"结晶蜂蜜粉"形式传入欧洲，现代美国人年均摄入蔗糖超120磅。尽管感官生物学研 究取得长足进步，大脑将甜味信号转化为实际摄食行为的精确机制仍未完全阐明。 味觉系统通过"专用通路"(labeled lines)硬连接触发与生俱来的行为反应(如偏爱甜味、排斥苦味)，这一过程无需学习或经验积累，但会受机体 内部状态与营养需求的显著影响。例如，饥饿状态下动物对甜味的偏好大幅增强，正常情况下令人厌恶的高浓度盐在缺钠时反而变得有吸引 力。此外，GLP1R激动剂等减重 ...

以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 近年来，随着GLP-1药物掀起的减重热潮，全球制药行业对减肥管线的投入热情空前高涨。面对GLP-1类药物存在的潜在副作用挑战，各大药 企纷纷布局差异化赛道，开发多元机制的减重方案。在注射剂、口服药等传统剂型之外，亦诺微基于其独创OVPENS平台推出了一款突破性外 用减肥产品MVR-EX105（简称EX105）——首个实现局部涂抹的非侵入性外泌体减肥疗法。近期公布的健康人试验数据显示，36名受试者通 过腹部局部使用EX105成功实现精准塑形——腹部体积平均缩减183.9cm³，腰围平均减少3.4cm，初步验证了该技术的有效性。该研究成果已 入选2025年国际肥胖与代谢病外科联合会（IFSO）年会壁报展示。 据亦诺微介绍，EX105基于其专有OVPENS平台开发，采用白色脂肪棕色化机制实现减脂效果。该产品以工程化外泌体作为生物源纳米递送系 统，通过精准设计在外泌 ...

Core Viewpoint - The article discusses the positive opinion from the European Medicines Agency (EMA) regarding the conditional marketing authorization for Novo Nordisk's semaglutide (Kayshild) for the treatment of non-alcoholic steatohepatitis (MASH) with liver fibrosis, marking a significant development in the GLP-1 receptor agonist market [5][7]. Group 1: Regulatory Developments - The EMA's Committee for Medicinal Products for Human Use has recommended Kayshild for conditional approval, which would make it the first GLP-1 receptor agonist approved in Europe for MASH [5][7]. - Semaglutide, initially approved for type 2 diabetes under the brand name Ozempic, has shown significant weight loss effects and was later approved as Wegovy for obesity management in the U.S. [7]. Group 2: Market Potential - The approval of semaglutide for MASH could reshape a potential market worth billions, as there are currently no widely available drug treatments for MASH [8]. - The combined effects of metabolic improvement and weight loss from GLP-1 drugs are attracting attention from the pharmaceutical and investment sectors [8]. Group 3: Mechanism of Action - Semaglutide works by promoting insulin secretion, inhibiting glucagon release, and regulating appetite through central nervous system action, leading to reduced energy intake and weight loss [7][15].

Core Viewpoint - Obesity is becoming one of the most systemic public health risks globally, significantly increasing the incidence of non-communicable diseases such as type 2 diabetes and cardiovascular diseases, thus straining healthcare systems and financial resources [4] Group 1: GLP-1 Receptor Agonists - GLP-1 receptor agonists have evolved from diabetes treatment drugs to key tools in managing obesity and its complications, showing clear weight loss and cardiometabolic benefits in multiple randomized controlled trials [4] - A recent study published in The Lancet Diabetes & Endocrinology assessed the potential population size for GLP-1 receptor agonists in obesity treatment, integrating health survey data from 99 countries covering over 810,000 non-pregnant adults aged 25 to 64 [5] - The study defined eligibility for GLP-1 receptor agonists based on BMI thresholds, with a general standard of BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with hypertension and/or diabetes, adjusting thresholds for Southeast Asia, East Asia, and South Asia due to increased metabolic risks at lower BMI levels [5] Group 2: Potential Patient Population - Approximately 27.0% of adults globally meet the medical criteria for GLP-1 receptor agonists for weight management, translating to a potential population size of about 799 million people, indicating that one in four adults may be medically suitable for this treatment [6] - The proportion of individuals who should use GLP-1 receptor agonists varies significantly by income level, with high-income countries at 41.8% and low-income countries at 11.7%, while nearly four-fifths of the potential patient population is concentrated in middle-income countries [6] - The regional distribution shows the highest applicability in Europe and North America at 42.8%, while Southeast Asia, East Asia, and South Asia, despite a lower applicability rate of 23.1%, have the largest absolute number of potential patients, approximately 639 million [6] Group 3: Demographic Characteristics - Among demographic characteristics, the proportion of women meeting medication standards is 28.5%, higher than men's 25.5%, with the percentage increasing significantly with age, reaching 38.3% in the 55 to 64 age group [7] - Income and education levels correlate with medication eligibility, showing a contrasting trend in different economies: higher income correlates with higher eligibility in low and middle-income countries, while in high-income countries, lower-income groups have the highest eligibility [7] Group 4: Challenges and Recommendations - The study highlights the substantial theoretical and medical demand for GLP-1 receptor agonists in global obesity prevention and treatment, but real-world implementation faces significant challenges, particularly in middle-income countries where data on drug accessibility and usage is limited [7] - The high cost of these medications poses a barrier to widespread adoption in the short term, with uncertain long-term impacts on healthcare budgets [7] - The authors emphasize that GLP-1 receptor agonists should not be viewed as a singular solution to obesity; a multifaceted approach combining drug treatment with structural long-term strategies is necessary to address the global obesity epidemic [8]

整理 | GLP1减重宝典内容团队 *本文仅供医疗卫生专业人士参考 版权声明：所有「GLP1减重宝典」的原创文章，转载须联系授权，并在文首/文末注明来源、作者、微信ID，否则减重宝典将向其追究法律责 任。部分文章推送时未能与原作者或公众号平台取得联系。若涉及版权问题，敬请原作者联系我们。合作事宜，请添加微信：andyxu365、 奥科达医药 正式递表港交所。1月26日，公司港股IPO申请获得受理，招股书在港交所官网披露。随着招股书公开，这家以改良型新药为核心战 略的特色制药企业，首次系统性展示了其技术平台、产品管线及未来增长逻辑，其中鼻用GLP-1受体激动剂项目成为最受关注的看点之一。 成立于2012年3月的奥科达医药，是一家研发驱动型制药公司，专注于利用已知安全特性的成熟分子，通过剂型与给药方式改良开发新一代治 疗方案。公司在中国上海和美国新泽西设有双研发及生产中心，业务覆盖研发、生产及商业化全产业链，重点布局中枢神经系统疾病、代谢性 疾病及罕见病等领域。 围绕差异化给药技术，奥科达医药已搭建起三大专有平台体系，包括面向儿童用药的AucPed平台、缓控释制剂平台AucTrol，以及鼻用给药平 台AucMis ...

以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 在减肥期间，节食带来的饥饿感常常令人难以忍受，但你或许不知道，这种饥饿不仅仅代表身体渴望补充食物，它还可能在无形中重塑着我们 的免疫系统。 近期，英国曼彻斯特大学研究团队在《Science Immunology》杂志上发表了一项前沿研究，揭示大脑对饥饿的感知能够独立于实际营养水平， 直接驱动免疫细胞的调节变化。 这一发现不仅动摇了传统关于饥饿和免疫关系的观点，也为多种疾病的治疗提供了全新思路。 研究背景：饥饿感隐藏的免疫通道 一直以来，科学界普遍认为生物体的代谢状态——如禁食或进食——会影响免疫细胞的变化，而这种作用多被视为营养水平改变的直接结果。 例如，禁食时因营养摄入降低，免疫系统的行为必然会发生变化。然而，这一观点始终无法解释为何即便在营养充足的前提下，只要让身体产 生饥饿感，免疫系统同样会产生类似变化。 从机制上看，AgRP神经元可以通过交感神经线路 ...