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。 作为科学界年度盛事，诺贝尔奖不仅是对卓越研究的至高褒奖，更是映照科学发展的晴雨表，因此每年颁奖季总能引发全球瞩目，2024年尤为 如此。 今年诺贝尔奖引发空前热议的关键在于，物理学奖与化学奖均授予了与人工智能密切相关的研究者——AI领域泰斗Geoff Hinton（曾任谷歌副 总裁十年）以及谷歌DeepMind联合创始人兼CEO Demis Hassabis和高级科学家John M. Jumper。毫无疑问，此次诺贝尔奖的最大赢家非"谷 歌"莫属。 谷歌的科研触角早已延伸至生命科学领域。2013年成立的谷歌旗下抗衰老公司Calico Life Sciences一直专注研究衰老与寿命的生物学机制，开 发延缓衰老和治疗相关疾病的干预手段。近期，Calico研究团队联合美国杰克逊实验室和宾夕法尼亚研究人员在顶级期刊《自然》发表重磅成 果，全面揭示了饮食限制对健康与 ...

整理 | GLP1减重宝典内容团队 研究人员指出，这一发现可能会影响未来2型糖尿病的治疗指南，使其更重视兼具控糖和神经保护作用的药物选择。 此前已有研究表明，GLP-1受体激动剂和二甲双胍都可能对糖尿病患者的大脑功能有保护作用。然而，迄今为止尚无大规模现实数据对比这两 类药物在降低痴呆风险方面的效果——而2型糖尿病患者患痴呆的风险比普通人群高出近70%。 ▍GLP-1减肥神药，减重降糖外还能抗痴呆 最新研究显示，用于治疗2型糖尿病的GLP-1受体激动剂，可能在预防痴呆方面优于目前广泛使用的二甲双胍。该研究是同类中规模最大的一 项，发表于《BMJ Open Diabetes Research & Care》开放获取期刊。 结果显示，作为一线治疗时，两类药物在降低血管性痴呆方面的效果没有显著差异。但GLP-1受体激动剂在整体预防痴呆方面效果更佳：约 2.5%（2,130人）的GLP-1使用者被诊断为痴呆，而二甲双胍组的发病率接近5%（4,215人），相对风险下降约10%。 具体来看，GLP-1药物使用者患阿尔茨海默病的风险降低了12%，患非血管性痴呆的风险则降低了25%。 点击关注，追踪最新GLP-1资讯 为进一 ...

整理 | GLP1减重宝典内容团队 受此消息影响，多家药企股价当日下跌，其中辉瑞、礼来和吉利德科学跌幅约2%，纽约泛美制药指数下跌3%。 特朗普在信中提出明确要求：所有药企必须向美国政府医疗补助项目（Medicaid）的患者提供"最惠国价格"，即OECD国家中最低的定 价。此外，新药也应执行相同政策。同时，企业需承诺不得向其他发达国家提供低于美国的售价。 他还要求企业将因国外高定价而获得的超额利润返还给美国患者和纳税人，方式是与政府签订返还协议。为打击中间商加价行为，特朗 普还提出支持企业直接面向患者销售药品，但前提是执行"最惠国"定价。 美国总统特朗普日前向17家大型制药企业的首席执行官发出公开信，要求他们将美国处方药的价格降低至与国际市场接轨，尤其是与其 他发达国家一致。白宫证实，这一行动是特朗普行政命令的一部分，旨在压制美国持续高企的药品费用。 今年5月，特朗普签署了一项行政命令，要求药企将药品价格与国际最低价格对齐，否则政府将通过立法、行政规则，甚至允许从海外 进口低价药品等手段干预市场。 收到信件的企业包括礼来、赛诺菲、再生元、默沙东、强生、阿斯利康等全球领先的制药公司。特朗普在信中表示："大多数药 ...

Core Viewpoint - The Danish pharmaceutical giant Novo Nordisk has lowered its full-year sales and profit forecasts due to slowing growth of its key drugs in the U.S. market, particularly Wegovy and Ozempic, amid increased competition and regulatory challenges [2][4]. Group 1: Sales and Profit Forecasts - The company now expects sales growth for the year to be between 8% and 14% on a constant currency basis, down from the previous forecast of 13% to 21% [2]. - Operating profit growth expectations have been revised from 16% to 24% down to 10% to 16% [2]. Group 2: Market Challenges - The downward adjustment in sales expectations for Wegovy in the U.S. is attributed to the widespread use of mixed formulations of semaglutide and slower-than-expected market expansion, along with intensified competition [4]. - The company faces challenges in the U.S. Wegovy market, particularly due to increased competition from mixed formulations of semaglutide that have gained popularity following FDA rulings on drug shortages [4]. Group 3: Regulatory and Safety Concerns - Despite the FDA's set deadline for large-scale compounded drugs ending on May 22, 2025, illegal and unsafe compounded medications remain prevalent in the market, posing significant health risks to patients [4][5]. - Novo Nordisk is actively pursuing legal actions to protect patients from counterfeit drugs and has expressed high concern over the ongoing circulation of unregulated GLP-1 compounds [5]. Group 4: Future Outlook - The company previously indicated that with increased regulatory enforcement, the supply of these generic drugs is expected to gradually decrease in the second half of the year, potentially alleviating competitive pressure [6]. - Disappointing clinical trial results, particularly for the new obesity treatment candidate CagriSema, have further weakened market expectations for the growth of its obesity treatment product line [8].

Core Viewpoint - The article discusses the rising popularity of ketogenic diets and presents new research findings that reveal the mechanisms behind weight loss associated with this diet, particularly focusing on the role of specific bile acids and gut microbiota [5][15]. Group 1: Mechanisms of Ketogenic Diet - Ketogenic diets induce the production of ketone bodies, prompting the body to utilize fat as an energy source, but recent studies indicate that the weight loss mechanisms are more complex [5]. - Research from Fudan University shows that ketogenic diets alter gut microbiota composition, leading to decreased levels of bile salt hydrolase (BSH), which results in increased levels of taurodeoxycholic acid (TDCA) and taurocholic acid (TUDCA) in the bloodstream [5][6]. - TDCA and TUDCA inhibit the expression of intestinal carbonic anhydrase 1, directly blocking calorie absorption [5][12]. Group 2: Clinical Observations and Findings - A clinical study involving over 400 participants confirmed the findings, suggesting that TDCA and TUDCA could serve as potential drug targets for treating obesity and its complications [6]. - In a 7-week study on mice fed a high-fat ketogenic diet (75.1% fat), significant reductions in body weight and fasting blood glucose were observed, alongside an increase in 22 metabolites, including six bile acids [9]. - The study also indicated that the presence of certain bile acids, particularly TDCA and TUDCA, plays a crucial role in the weight loss effects of the ketogenic diet [9][14]. Group 3: Gut Microbiota and Weight Loss - Analysis of the gut environment in mice revealed that the levels of TDCA and TUDCA are closely related to gut microbiota changes, with specific strains like Lactobacillus murinus ASF361 significantly impacting body weight and blood glucose levels [11][12]. - The study found that L. murinus ASF361 reduces serum levels of TDCA and TUDCA by metabolizing them into other bile acids, which suggests a complex interaction between diet, gut bacteria, and metabolic outcomes [12]. Group 4: Human Study Correlation - Data from 416 healthy participants indicated a correlation between low plasma levels of TDCA and TUDCA with high BMI and fasting blood glucose levels [14]. - Participants in a 12-week ketogenic diet study lost an average of 5.27 kg, with significant increases in plasma TDCA and TUDCA levels, aligning with findings from mouse experiments [14].

以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 深度分享内分泌用药经验、病例剖析、指南专业解读并紧跟国内外内分泌领域前沿进展，「每医健」旗下内容平台。 国际权威期刊《柳叶刀》子刊eBi oMe di c i ne发表突破性研究指出：你的晚餐时间可能早就刻在DNA里——但提前开饭却能显著降低糖 尿病风险，这记"基因时钟"与"代谢警报"的双重暴击，正在颠覆传统健康认知。 研究团队发现： 1. 遗传基因暗中操控着我们的进食时间偏好 2. 每推迟1小时进餐，血糖波动风险激增 3. 提早进食可打破"肥胖-高血糖"恶性循环 ▍ 生物钟决定最佳吃饭时间？《柳叶刀》子刊最新研究揭秘 这项发表在《柳叶刀》子刊的研究，首次通过92对双胞胎的精密实验，结合5天饮食记录+葡萄糖耐量测试（OGTT），破解了"吃饭时 间"的代谢密码。 核心发现： ✅ 即使排除睡眠、年龄、性别等因素， 晚吃依然拉高BMI和腰围 你以为吃饭只是填饱肚子？错！最新科学研究发现，进食时间竟能直接影响血糖代谢和糖尿病风险——而这一切，可能早就被你的基因 安排得明明白白。 生物钟：藏在身体里的"代谢指挥官" 人体生物钟不仅控制睡眠，更是代谢系统的 ...

Core Viewpoint - Semaglutide, marketed as a weight loss drug, has gained popularity among users who report significant weight loss and improved body composition after using it for a short period [2]. Group 1: Product Approval and Mechanism - Semaglutide tablets have been approved for use in China for the treatment of type 2 diabetes in adults by the National Medical Products Administration (NMPA) in 2024 [3]. - The drug works by activating GLP-1 receptors, which helps lower blood sugar and body weight through multiple mechanisms, including promoting insulin secretion, inhibiting glucagon secretion, delaying gastric emptying, and suppressing appetite [4]. - Semaglutide oral tablets are the first GLP-1 receptor agonist available in oral form, significantly enhancing bioavailability by approximately 100 times due to the absorption enhancer SNAC [4]. Group 2: Clinical Research Findings - The global PIONEER clinical trial, involving 11,505 patients, demonstrated that semaglutide not only significantly lowers blood sugar but also provides benefits in weight loss, blood pressure reduction, and lipid regulation [6]. - In the PIONEER 6 study, semaglutide oral tablets showed excellent cardiovascular safety, particularly in patients with cardiovascular diseases or risk factors [6]. - The PIONEER PLUS trial results indicated that higher doses of semaglutide (25mg and 50mg) resulted in greater reductions in HbA1c levels and weight loss compared to the 14mg group, with weight loss averaging 7.0kg and 9.2kg respectively [7]. Group 3: Weight Loss Efficacy - The OASIS 4 study revealed that participants using semaglutide experienced an average weight loss of 13.6%, compared to only 2.2% in the placebo group, with potential weight loss reaching 16.6% if all participants completed the treatment [9].

Core Viewpoint - The article highlights the alarming rise in global diabetes prevalence, with over 800 million adults affected, and emphasizes the urgent need for improved public health strategies and early intervention, particularly in high-risk populations like China [5][9][10]. Group 1: Global Diabetes Trends - The total number of global adult diabetes patients has surpassed 800 million, a fourfold increase since 1990, with 4.45 million untreated patients aged 30 and above in 2022 [5][9]. - By 2050, global diabetes patients are projected to exceed 1.31 billion, indicating a significant public health challenge ahead [7]. - The global diabetes prevalence rate increased by 90.5% from 1990 to 2021, rising from 3.2% to 6.1% [7]. Group 2: Diabetes in China - China has 148 million diabetes patients, ranking second globally, with over 52% of these patients untreated [9][10]. - The majority of new diabetes cases in China are type 2 diabetes, accounting for 99.2% of new cases in 2021 [10]. - The gender disparity in diabetes-related health burdens is notable, with men experiencing a higher disability burden compared to women [10]. Group 3: Complications and Healthcare Burden - Approximately 30% to 40% of diabetes patients may develop chronic kidney disease (CKD), with type 2 diabetes being a major contributing factor [8]. - The number of new CKD cases due to type 2 diabetes rose from 1.4 million in 1990 to 2.4 million in 2017, a 74% increase [8]. - The treatment resources for end-stage kidney disease (ESKD) are unevenly distributed globally, with only 27% to 53% of patients receiving necessary care [8]. Group 4: Prevention and Control Strategies - The updated "China Diabetes Prevention and Control Guidelines (2024)" indicates a continuous rise in diabetes prevalence, necessitating enhanced screening and diagnostic measures [11][12]. - The national health initiative aims to increase diabetes awareness and screening rates, targeting a 60% awareness rate among adults by 2030 [12][13]. - The guidelines emphasize the importance of regular blood sugar testing for high-risk groups and the need for improved healthcare capabilities at the grassroots level [12][13].

Core Insights - The article highlights the performance of pharmaceutical companies in the 2025 Fortune Global 500 list, with Merck, Novo Nordisk, and Johnson & Johnson being notable entries, showcasing the strength of the pharmaceutical sector [2][3]. Pharmaceutical Sector Performance - The total revenue of the 500 companies in the 2025 Fortune Global 500 list is approximately $41.7 trillion, accounting for one-third of global GDP, with a year-on-year increase of 1.8%. The total net profit is $2.98 trillion, showing a slight increase of 0.4% [2]. - The entry threshold for the list is $32.2 billion, which has slightly increased compared to the previous year [2]. - Among the top 50 most profitable companies, three are pharmaceutical firms: Merck, Novo Nordisk, and Johnson & Johnson. Notably, Merck and Novo Nordisk are making their debut on the list, while Novartis has dropped out [2]. Financial Performance of Key Companies - Merck reported a net profit of $17.117 billion, with a remarkable growth rate of 45.9% [3]. - Novo Nordisk achieved a net profit of $14.644 billion, reflecting a growth of 20.6% [3]. - Johnson & Johnson's net profit stands at $14.066 billion, indicating stable growth [3]. - Merck's revenue is significantly driven by its PD-1 cancer drug, Keytruda, which accounts for nearly one-third of its total revenue [3]. - Novo Nordisk's sales surged to $29.3 billion, a 38% increase, primarily due to its semaglutide product line, including Ozempic, Wegovy, and Rybelsus [3]. Novo Nordisk's Market Position and Challenges - Novo Nordisk's revenue for the 2024 fiscal year is reported at 290.4 billion Danish Krone (approximately $42.1 billion), with a net profit of 100.9 billion Danish Krone (approximately $14.64 billion), well above the entry threshold of $32.2 billion [5]. - The company boasts a profit margin of approximately 36%, placing it among the leaders in the global pharmaceutical industry [5]. - In terms of revenue ranking, Novo Nordisk is positioned within the top ten globally, following giants like Johnson & Johnson, Roche, Pfizer, and Merck [6]. Product Performance and Market Dynamics - The semaglutide product line is identified as the primary growth driver for Novo Nordisk, with total sales reaching $29.3 billion, contributing to over 25% growth in overall revenue [7]. - In Q1 2025, semaglutide sales hit $7.864 billion globally, surpassing Merck's Keytruda sales of $7.2 billion, temporarily making it the "king of drugs" [7]. Market Pressures and Strategic Adjustments - Novo Nordisk has revised its 2025 performance forecasts downward, with sales growth expectations adjusted from 13%-21% to 8%-14%, and operating profit expectations reduced from 16%-24% to 10%-16% [9]. - The downward revision is attributed to a slowdown in the U.S. market, increased competition from Eli Lilly's Mounjaro and Zepbound, and the widespread circulation of compounded GLP-1 drugs [9]. - Despite a 18% quarterly sales growth reported in Q2, the market reaction has been weak [10]. Leadership Changes and Strategic Focus - The company experienced a significant stock price drop of 21.8%-23% on July 29, resulting in a market value loss of over €6 billion, marking its largest single-day decline in history [11]. - In May, Novo Nordisk dismissed CEO Lars Fruergaard Jørgensen, appointing Maziar Mike Doustdar as the new CEO effective August 7, focusing on enhancing commercial execution and cost efficiency in the U.S. market [12]. - The company is also taking legal action against the proliferation of compounded drugs and is accelerating the establishment of official self-operated channels, such as NovoCare services, to address market chaos and improve the penetration of legitimate prescription channels [13]. Future Outlook - Novo Nordisk's strong performance in 2024, driven by its semaglutide product line, has positioned it among the most profitable pharmaceutical companies globally [14]. - However, the company faces significant challenges in the short term due to rising competition, declining market expectations, and regulatory issues related to compounded drugs [14]. - The new CEO Doustdar will need to navigate the pressures of reshaping the U.S. market while aiming to restore confidence through optimized execution and strengthened legitimate channels [14]. - If Novo Nordisk can successfully expand production capacity, control the circulation of counterfeit drugs, and maintain innovation in research and development, it is likely to solidify its leading position in the global pharmaceutical industry [15].

Core Viewpoint - The article emphasizes the urgent need for a national initiative to combat obesity in China, highlighting the alarming statistics and health risks associated with rising obesity rates, which have become a public health crisis rather than just an individual concern [3][5][10]. Group 1: National Initiatives and Guidelines - The National Health Commission has launched the "Weight Management Year" initiative to address the obesity crisis through comprehensive societal collaboration and policy design [5][7]. - The "Weight Management Guidelines (2024 Edition)" aim to promote scientific weight loss concepts and enhance health services, dietary habits, and exercise facilities [5][7]. - By 2024, the number of overweight and obese individuals aged 25 and above in China reached 402 million, with projections indicating this could rise to 627 million by 2050 if no action is taken [5][10]. Group 2: Obesity Statistics and Trends - China has transitioned from being known as a "thin country" to having the largest population of overweight individuals globally, with over 400 million affected [7][10]. - By 2030, it is projected that 70.5% of adults and 31.8% of children in China will be overweight or obese, with significant increases in male and female obesity rates [3][10]. - The prevalence of abdominal obesity is concerning, with 14% of individuals with normal BMI classified as having hidden obesity, particularly among men [8][10]. Group 3: Health Consequences of Obesity - Obesity is linked to over 200 diseases, including type 2 diabetes, hypertension, and various cancers, significantly impacting public health and healthcare costs [10]. - The rise in obesity rates poses a threat not only to individual health but also to national economic stability, with potential increases in healthcare expenditures and workforce productivity losses [10][13]. - The article warns that the growing number of obese children, projected to reach 35.2 million, represents a future public health crisis [10][13]. Group 4: Call to Action - The article encourages individuals to take proactive steps in managing their weight, emphasizing the importance of measuring BMI and waist circumference as part of a broader public health initiative [13][15]. - The government and various sectors are working together to create a supportive environment for weight management, making healthier food options and exercise facilities more accessible [13][15].