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。 你最近检测过自己的血脂吗？根据《中国成人血脂管理指南（2023年）》的数据，2018年我国18岁及以上人群血脂异常的总患病率已高达 35.6%。这包括高胆固醇血症、高甘油三酯血症、混合型高脂血症以及低高密度脂蛋白胆固醇血症。 血脂异常在早期通常没有明显症状，但实际上血管已经在悄悄受损。随着病情进展，脂肪、胆固醇等物质在血管内逐渐沉积，形成"斑块"，导 致血管逐步硬化、变窄，进而大幅提升动脉粥样硬化性心血管疾病的风险。 很多人以为高血脂只是中老年人才需要担心的健康问题。事实上，过去针对动脉粥样硬化的筛查和防控，大多也是聚焦在50岁以上胆固醇偏高 的人群。 然而，最近《自然》杂志发表的新研究提醒我们，动脉粥样硬化的预防应更早开始，年轻时就要重视血脂管理，尤其要警惕高脂饮食在儿童和 青少年中的摄入。 在这项研究中，剑桥大学心肺研究所的科学家用小鼠做实验，探索高脂饮 ...

Core Insights - Terns Pharmaceuticals, Inc. has announced the topline results of its Phase 2 clinical trial for TERN-601, an oral GLP-1 receptor agonist aimed at treating obesity [2][6] Group 1: Key Trial Results - Participants using doses above 500 mg experienced a maximum placebo-adjusted weight loss of 4.6%, with statistically significant weight loss observed at higher doses [3] - Weight loss results by dosage: - TERN-601 250 mg: -1.8% placebo-adjusted - TERN-601 500 mg (slow titration): -3.6% placebo-adjusted - TERN-601 500 mg: -4.6% placebo-adjusted - TERN-601 750 mg: -3.0% placebo-adjusted - Placebo: No significant weight loss observed - p-values for 500 mg and 750 mg doses were below 0.01, indicating statistical significance [3] Group 2: Safety Profile - 12% of participants discontinued treatment due to adverse events (AEs), primarily gastrointestinal issues, with nausea being the most common [4] - Gastrointestinal AEs were generally mild to moderate, including nausea (56%), vomiting (26.9%), constipation (11.9%), and diarrhea (9.7%), and were dose-related but did not result in severe cases [4] - Three participants experienced grade 3 liver enzyme elevations post-treatment, with two possibly related to the drug, consistent with drug-induced liver injury (DILI) [4] Group 3: Strategic Shift - Despite some treatment groups showing weight loss effects, the trial results did not meet the high standards for safety, efficacy, and tolerability required for a differentiated oral GLP-1RA treatment [6] - Consequently, Terns Pharmaceuticals has decided to discontinue the development of TERN-601 and will not pursue further investments in metabolic diseases [6] - The company will refocus on TERN-701, an allosteric BCR-ABL inhibitor for chronic myeloid leukemia (CML), with confidence in the ongoing Phase 1 CARDINAL trial and expects to release related data this quarter [6]

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。 以下文章来源于内分泌早知道 ，作者关注肥胖的 内分泌早知道 . 传统观念一直将高热量美食视为肥胖元凶，但加州大学伯克利分校St e pha n Lamme l团队在《自然》期刊发表的最新研究彻底颠覆了这 一认知。该研究题为《神经降压素信号变化驱动肥胖中的快感贬值》，首次揭示进食过程中的愉悦感受对维持健康体重具有不可忽视的 积极作用。令人惊讶的是，即便是火锅、炸鸡、奶茶、蛋糕这类被贴上"垃圾食品"标签的高油高糖食物，其带来的正向饮食体验同样能 成为体重管理的潜在助力。这项突破性研究不仅阐明了肥胖形成的神经生物学机制，更为全球肥胖防治提供了革命性的科学视角。 研究团队通过精密的神经科学实验发现，当大脑接收美食带来的愉悦信号时，会激活特定的神经调控通路，这种正向反馈实际上有助于 维持能量代谢平衡。这一发现完全颠覆了"美味必然导致肥胖"的简单线性思维，将饮食快感从肥胖诱因重新定义为代谢调节的重要环 节。该成果为开发新型肥胖干预策略奠定了理论基础，未来或可通过调节饮食愉悦相关的神经信号通路来实现更科学有效的体重管理。 ...

Core Viewpoint - The article discusses the emergence and effectiveness of GLP-1 receptor agonists as a dual solution for obesity and diabetes, highlighting their mechanisms, clinical trial results, and future prospects in weight management and glycemic control [4][6][18]. Summary by Sections Introduction to Obesity and Diabetes - Obesity is a common comorbidity in diabetes, worsening insulin resistance and complicating blood sugar control. Traditional diabetes medications often lead to weight gain, creating a vicious cycle. The introduction of GLP-1 receptor agonists offers a potential solution to address both obesity and diabetes simultaneously [4]. What are GLP-1 Receptor Agonists? - GLP-1 (Glucagon-like peptide-1) is an incretin hormone that promotes insulin secretion, inhibits glucagon release, and delays gastric emptying, contributing to blood sugar control and appetite suppression. However, reduced GLP-1 secretion and action are observed in both diabetic and non-diabetic obese patients [6][7]. Efficacy of Liraglutide - Liraglutide, approved by the FDA in 2009 for type 2 diabetes under the brand name Victoza®, has shown significant weight loss effects in clinical trials. In a study with 564 participants, those receiving liraglutide lost between 4.8 kg to 7.2 kg compared to 2.8 kg and 4.1 kg in placebo and orlistat groups, respectively [9][10]. Over a year, liraglutide users lost an additional 5.8 kg compared to placebo [11]. By 2014, liraglutide was also approved for weight management under the brand name Saxenda® [12]. Emergence of Semaglutide - Semaglutide, introduced in 2017 under the brand name Ozempic®, requires weekly injections and has demonstrated superior weight loss results. In the STEP trials, semaglutide users lost an average of 15% of their body weight, significantly outperforming placebo groups [13][15]. The STEP 1 trial showed a 14.9% weight reduction, with over one-third of participants losing more than 20% of their weight [15]. The FDA approved semaglutide for obesity management in June 2021, marking it as the first new drug for obesity since 2014 [17]. Future Prospects - Oral formulations of semaglutide are being explored, primarily for type 2 diabetes treatment, with ongoing studies demonstrating its efficacy in weight loss and metabolic regulation. The PIONEER trials showed significant reductions in HbA1c and body weight among participants [20][21]. The potential for oral administration may provide an alternative for patients averse to injections [18]. Conclusion - The article emphasizes the importance of lifestyle changes alongside medication for effective weight management, underscoring that pharmacotherapy should complement healthy living rather than replace it [21].

整理 | GLP1减重宝典内容团队 诺和诺德正在经历一次重要的领导层过渡，这一变动是由公司最大股东——Novo基金会推动的，该基金会呼吁采取更加激进的措施来 振兴这家丹麦制药巨头。根据变动，董事会主席Helge Lund和另外六名董事成员将辞职，前CEO Lars Rebien Sørensen将再次担任 CEO，并同时担任基金会的首席执行官。 Sørensen曾在2000年至2016年期间担任Novo Nordisk的CEO，他在周二的电话会议中对公司的未来表示信心。他表示："在Mike Doustdar担任新CEO的情况下，实施中的转型计划和重新组成的董事会，我相信Novo Nordisk有一支强大的领导团队，完全致力于成 功。" 随着Sørensen的回归，公司将更加受到Novo基金会的控制，基金会是一个慈善组织，拥有Novo Holdings，并通过它管理基金会的投 资，持有Novo Nordisk和Novonesis的控股权。Sørensen计划在CEO职位上停留两到三年，但他强调，基金会不打算长期参与："这不 是我们希望的治理结构。" 根据周二的公告，诺和诺德将在11月召开临时股东大会（EGM）， ...

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。 肥胖不仅是身材问题，更是健康"隐形杀手"！世界卫生组织早已将肥胖列为十大慢性疾病之一，它与代谢异常、心脑血管疾病、慢性肾 病乃至多种癌症都密切相关。最新研究发现，肥胖还会对大脑造成不可逆的损伤！ ◆ BMI指数暗藏健康密码 ▍中国近半人口面临超重困扰 最新数据显示，我国超重和肥胖人群比例高达49%。虽然我国不是肥胖率最高的国家，但庞大的人口基数使我们成为全球肥胖人口最多 的国家。这个数字背后，隐藏着巨大的健康危机。 国际通用的身体质量指数（BMI）是衡量肥胖程度的重要指标，计算公式为：体重（kg）÷身高²（m²）。国际标准将BMI 1 8.5- 25视 为正常范围，超过2 5为超重，30以上则达到肥胖标准。需要注意的是，中国采用更严格的BMI标准：1 8.5- 23.9为正常，24- 27.9为超 重，≥2 8即属于肥胖。 ◆ 惊人发现：肥胖让大脑提前衰老 首都医科大学最新研究揭示，体重超标会导致大脑白质病变加剧，脑容量缩小。更令人震惊的是， ...

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。 肥胖已成为当今社会普遍存在的健康难题，深入了解其生物学机制，对于研发更有效的肥胖治疗手段至关重要，这也让我们有望摆脱单纯"少 吃"来防治肥胖的传统思路。 目前，主流的减肥方法多以抑制食欲为核心，但这种方式往往会导致身体自动降低能量消耗，结果就是体重反复反弹。即使是目前流行的 GLP-1类减肥药（如司美格鲁肽），停药后体重回升依然十分常见。 虽然控制饮食对减肥有帮助，但想要获得更持久的效果，提高能量消耗同样不可或缺。特别是在某些类型的肥胖中，能量消耗的作用甚至超过 了能量摄入。 2024年8月28日，牛津大学Ana I. Domingos团队（博士生Yitao Zhu为第一作者）在国际权威期刊《Nature》发表了题为"Sympathetic neuropeptide Y protects from obesity by sustaining thermoge ...

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。 虽然身体成分常被误解为被动的脆弱指标，实际上它们积极参与整体代谢调节，在应对急性损伤后的生存中起到关键作用。危重症时，肌肉 与脂肪组织会发生显著调整，这不仅影响住院期间，还会深刻改变出院后的代谢状态。肥胖对全身代谢和病人预后的影响仍有争议。各种底 物诱导的表观遗传变化会改变基因表达谱，进而影响那些直接关联患者生存的代谢路径。 本文综述了 危重症中，从体重调节到免疫反应执行阶段，能量如何在体内流动的核心机制。同时也提出，未来研究应着重于受损的免疫代 谢和表观遗传机制，以期更深入理解其本质，并为危重病人带来更好的治疗预后 。 在危重症过程中，全身炎症会引发器官间特有的代谢变化。在免疫及炎症相关区域，合成代谢的重新编程主要用于支持细胞增殖和完成炎症 反应。同时，脂肪组织和骨骼肌的分解代谢为免疫和炎症细胞的合成代谢提供了必要的碳源和能量。在这些代谢调整中，肝脏至关重 ...

Core Viewpoint - The article emphasizes the risks associated with using the remaining medication in GLP-1 injection pens, referred to as the "golden dose," and advises proper disposal instead of usage [4][11][12]. Summary by Sections GLP-1 Drug Overview - GLP-1 drugs like Ozempic and Mounjaro are widely recognized for their weight loss effects and are also used to treat type 2 diabetes. Specific GLP-1 medications such as Zepbound and Wegovy are designed solely for weight loss [6]. Usage Statistics - As of 2024, approximately 12% of American adults have used GLP-1 drugs, with prescriptions for obesity treatment increasing by 586.7% from 2019 to 2024 [7]. "Golden Dose" Explanation - The "golden dose" refers to the small amount of medication left in the injection pen after the prescribed doses have been administered. For instance, a Mounjaro pen contains 2.4 milliliters, with each dose using 0.6 milliliters, leaving a small residual amount [9]. Risks of Using the "Golden Dose" - Experts strongly advise against using the remaining medication as it poses significant risks, including potential underdosing or overdosing, which can lead to adverse effects such as nausea, vomiting, diarrhea, or constipation [9][11]. - The remaining liquid is not a usable dose but a built-in buffer to ensure accurate dosing during injections [9]. Manufacturer Warnings - The manufacturers of Mounjaro warn that attempting to use the remaining medication can lead to contamination risks, including infections and abscesses, which could escalate to severe conditions like sepsis [11]. Proper Disposal Guidelines - It is recommended to discard the injection pen after completing the prescribed doses, regardless of any remaining medication. Users should safely dispose of the pen and needle to prevent health risks [12]. Misconceptions About Dosage - Some users may believe that using leftover medication will accelerate weight loss; however, experts caution that increasing the dosage too quickly can lead to severe side effects and that medications should be titrated gradually [12]. Importance of Medical Guidance - Patients are encouraged to consult healthcare professionals before making any adjustments to their medication regimen, as self-adjustment can lead to health risks [12].

Core Viewpoint - CVS Health Ventures is strategically investing in Knownwell, a primary care platform focused on metabolic health, aiming to shift obesity treatment from solely medication to comprehensive chronic disease management [2][4]. Group 1: Investment and Business Model - CVS Health Ventures led a $25 million strategic financing round for Knownwell, which has raised over $50 million to date [2][4]. - Knownwell's business model contrasts with traditional GLP-1 weight loss platforms by emphasizing a doctor-led comprehensive management approach, integrating nutrition counseling, behavioral health, and remote monitoring [4]. - The investment reflects a structural shift in the U.S. obesity treatment market, recognizing Knownwell's patient-centered and outcome-oriented model [4]. Group 2: Collaboration and Market Dynamics - Knownwell collaborates with Eli Lilly's LillyDirect platform to expand its service offerings, providing personalized health and weight management services covered by insurance [7]. - As the price of GLP-1 medications potentially decreases to $150 per month, CVS Health Ventures' investment strategy is evolving, focusing on integrated care rather than just medication [7]. - Knownwell's model stands out by prioritizing overall health management and long-term outcomes, marking a transition from a medication-centric approach to a results-oriented comprehensive management model [7][8]. Group 3: Leadership Perspective - Knownwell's CEO, Brooke Boyarsky Pratt, emphasizes that respectful, evidence-based obesity care leads to unprecedented patient engagement and significant health improvements [5].