整理 | GLP1减重宝典内容团队 欧洲肥胖研究协会（EASO）近日发布最新指导意见，建议司美格鲁肽或替尔泊肽应成为肥胖及大多数相关并发症的首选药物。 这份《肥胖及并发症药物治疗框架》在Nature Medicine上在线发表，为临床医生提供一套算法，用以"将患者健康背景与药物作用机制 相匹配"，以便制定个体化治疗方案。 研究团队由国际肥胖领域专家组成，他们以患者是否存在肥胖相关并发症作为主要决策依据，并综合评估各药物在总体减重效果、并发 症改善及安全性等方面的表现。基于截至2025年1月的传统和网络荟萃分析结果，研究者指出：当目标是实现显著体重下降时，替尔泊 肽和司美格鲁肽应被视为"一线药物"。 作者将肥胖相关并发症分为两类： 共同作者、EASO肥胖管理工作组联合主席安德烈亚·丘丁（Andreea Ciudin）博士表示："虽然市面上已有多种药物可选，但从疗效角 度看，司美格鲁肽与替尔泊肽的效果远超其他药物，几乎应成为所有病例的首选。" ▍ "首选药物"的确定依据 脂肪负担性疾病（与机械性问题相关，如阻塞性睡眠呼吸暂停、膝骨关节炎） 病理性脂肪疾病（与代谢及免疫异常相关，如糖尿病前期、2型糖尿病、心血管疾病 ...

Core Insights - The article discusses a groundbreaking research published in "Science" that reveals a new signaling pathway in the brain's neurons, which plays a crucial role in appetite regulation and could lead to new anti-obesity strategies. Currently, obesity affects approximately 40% of adults in the U.S. and over 1 billion people globally [6][7]. Group 1: Research Findings - The research team, led by Dr. Zhao Zhang, discovered a previously unknown signaling pathway in the cilia of brain neurons that regulates appetite, presenting a new breakthrough for weight loss treatments [7]. - The rapid development of weight loss medications is transforming the healthcare industry, achieving lasting weight control and showing significant benefits in cardiovascular health, blood sugar balance, and management of blood pressure and cholesterol [7]. - The study utilized Automated Meiotic Mapping (AMM), a combination of genetics and machine learning, to efficiently locate gene mutations associated with obesity [8]. Group 2: Genetic Insights - The research identified the Gpr45 gene as central to weight regulation, with mutations leading to obesity in mice due to increased food intake [8]. - GPR45 protein is highly expressed in hypothalamic neurons and is involved in transporting Gαs protein to primary cilia, activating the MC4R signaling pathway to regulate appetite [9]. - Current medications targeting MC4R are limited to specific genetic mutations and do not apply to the broader obesity population, highlighting the potential for developing drugs that enhance GPR45 activity for wider treatment options [9].

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。 以下文章来源于内分泌早知道 ，作者关注内分泌的 全球肥胖问题持续加剧，中国超重及肥胖人群已突破6.1亿大关。在众多体重管理策略中，膳食干预作为生活方式调整的核心手段，低 碳水化合物饮食与限时进食模式因其显著效果备受科研界关注。 Ce ll Re p orts Me di c i ne最新发表了华中科技大学刘刚教授团队的重要研究成果，该研究通过为期12周的严格膳食干预试验，首次证实 即使在相同热量限制（减少25%）条件下，健康型低碳水膳食联合限时饮食仍能产生显著的额外减重效益 ，并揭示其对肠道微生物组 的深远影响。 这项创新性研究采用标准化供餐模式，发现干预结束后虽然出现预期中的体重回升现象，但健康型低碳水膳食的减脂效果具有显著持续 性， 在干预终止28周后仍能维持 。更值得关注的是，研究团队通过先进机器学习技术，成功鉴定出与减重效果高度相关的生物标志物 组合，并据此 开发出具有临床应用前景的预测模型 （已获国家发明专利保护，专利号CN202411331 775.7）。这些发现不仅为理解不 ...

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： ▍ 生物钟决定最佳吃饭时间？《柳叶刀》子刊最新研究揭秘 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"隐形操盘手"。虽然过去研究已发现晚餐太晚与肥胖、心血管疾病有关，但进食时间对血糖 和糖尿病的具体影响一直是个未解之谜。 双胞胎研究揭开关键证据 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： ▍ 震惊！你的吃饭时间竟被基因"操控"？科学揭秘背 ...

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 ...

Core Viewpoint - The article discusses the significant advancements in AI drug development, highlighting a transformative shift in the pharmaceutical industry where AI is moving from enhancing existing processes to enabling the creation of entirely new drug candidates through innovative design techniques [5][8][9]. Group 1: AI Drug Development Trends - AI drug development is gaining momentum, with several companies achieving substantial business development (BD) transactions, amounting to billions of dollars, indicating renewed investor confidence in the sector [6][7]. - Companies like YuanSi ShengTai and HuaShen ZhiYao have successfully navigated stringent selection processes of multinational pharmaceutical firms, demonstrating the effectiveness of AI in improving drug development success rates [6][7]. Group 2: Technological Advancements - The emergence of advanced AI models, such as AlphaFold 2, has revolutionized protein structure prediction, allowing for the rapid identification of protein structures that were previously difficult to obtain [10][11]. - New AI models, including Chai-2 and ESM3, have shown significant improvements in generating novel protein designs, enhancing the efficiency of drug discovery processes [11][12]. Group 3: Paradigm Shift in Drug Discovery - The traditional drug discovery process, characterized by extensive screening and empirical methods, is being replaced by a more rational and design-focused approach enabled by AI [9][13]. - AI's ability to design drugs from scratch (de novo design) is expected to unlock new therapeutic targets that were previously considered difficult to address, potentially leading to breakthroughs in treating chronic diseases [14][13]. Group 4: Industry Dynamics and Future Outlook - The article outlines three main types of players in the AI drug development space: tech giants with substantial resources, startup teams led by top AI and biological scientists, and traditional pharmaceutical companies leveraging AI for drug development [15][16]. - The future of drug development is anticipated to be heavily influenced by AI, with a focus on delivering viable drug candidates that meet market needs, thereby reshaping the competitive landscape of the pharmaceutical industry [17].

Core Viewpoint - The article discusses the advantages and mechanisms of the oral formulation of Semaglutide compared to its injectable counterpart, highlighting its convenience, adherence, and potential health benefits for weight management and metabolic health. Group 1: Advantages of Oral Semaglutide - Oral Semaglutide has higher adherence due to the elimination of injection steps, reducing fear and inconvenience associated with self-injection [5] - The oral formulation is more convenient to store at room temperature, while injectables require cold chain storage, which can lead to secondary contamination [6] - Oral dosing allows for easier adjustment of dosage in response to side effects or social situations, unlike injectables which cannot be adjusted once administered [6] Group 2: Mechanism and Effects - Semaglutide works by delaying gastric emptying and reducing appetite, acting on GLP-1 receptors found in various organs, including the brain and stomach [10] - Users can expect to see weight loss results within a month, typically ranging from 5% to 8% of body weight, depending on individual factors [13] - The drug has been shown to provide cardiovascular benefits, with significant effects observed over at least four years of treatment [14] Group 3: Usage Guidelines and Considerations - It is recommended to start with a lower dose of 7mg for those transitioning from injectable forms, regardless of the previous treatment purpose [11] - Semaglutide should be taken before the first meal of the day, as taking it at bedtime may interfere with absorption and sleep [12] - For individuals with normal blood sugar levels, the risk of hypoglycemia when using Semaglutide is low due to its glucose-dependent action [16] Group 4: Long-term Use and Other Benefits - Long-term use may be necessary for those who have not reached their weight loss goals, while those who have can maintain their weight with lower doses combined with lifestyle changes [17][18] - Semaglutide has additional benefits, including alleviating sleep apnea, hypertension, and non-alcoholic fatty liver disease, and may help prevent Alzheimer's disease and cardiovascular issues [22]

Core Insights - The article discusses the relationship between gut microbiota and exercise fatigue, suggesting that imbalances in gut bacteria can affect the metabolism of tryptophan, leading to decreased dopamine levels and reduced motivation for exercise [4][5][6]. Group 1: Understanding Exercise Fatigue - Exercise fatigue is influenced by two main factors: central fatigue (brain's inefficiency) and peripheral fatigue (muscle's energy depletion) [6]. - Central fatigue occurs when the central nervous system is unable to effectively command muscles, leading to a significant drop in endurance [6]. - Peripheral fatigue is caused by various factors, including energy depletion, low dopamine levels, ammonia interference, hormonal imbalances, metabolic waste accumulation, and muscle fiber damage [6][9]. Group 2: Tryptophan-Kynurenine Pathway - Tryptophan, an essential amino acid, plays a crucial role in regulating central fatigue through its metabolism, primarily via the kynurenine pathway [9][11]. - This pathway can lead to two outcomes: the production of kynurenic acid (which helps alleviate fatigue) and neurotoxic compounds that may exacerbate fatigue [9][11]. Group 3: Role of Gut Microbiota - Gut microbiota can influence tryptophan metabolism, thereby improving neurotransmitter synthesis, reducing lactic acid accumulation, and alleviating central fatigue [9][12]. - Short-chain fatty acids (SCFAs), produced by gut bacteria from dietary fibers, serve as an energy source for muscles and help clear lactic acid, enhancing recovery from exercise [12]. Group 4: Probiotics as a Solution - Probiotics are highlighted as effective in optimizing tryptophan metabolism, promoting the synthesis of neurotransmitters, and reducing lactic acid buildup [13][14]. - Specific probiotic strains have been identified for their unique benefits, such as enhancing endurance and reducing oxidative stress [20]. Group 5: Practical Recommendations - To support gut health and enhance exercise performance, it is recommended to consume whole grains, fresh vegetables, and legumes, which are rich in dietary fibers that promote SCFA production [12]. - The article emphasizes the importance of maintaining a healthy gut microbiome to improve overall physical performance and recovery [17].

Core Viewpoint - The article discusses the collaboration between Paig Bio and PDC FZ-LLC for the exclusive licensing of the innovative drug Visepagendide (PB-119), a GLP-1 receptor agonist aimed at treating type 2 diabetes and weight management in the Middle East and Africa [2][3][4]. Group 1: Product Overview - Visepagendide (PB-119) is a weekly administered GLP-1 receptor agonist developed by Paig Bio, showing good safety, tolerability, and significant effects on blood sugar reduction and weight loss in clinical studies [3]. - The product's innovative molecular structure and long-acting mechanism provide a more convenient and stable treatment option, positioning it as a representative of the next generation of GLP-1 therapies [3]. Group 2: Market Potential - The Middle East and Africa are rapidly growing markets for diabetes and obesity treatment drugs, with a high prevalence of related diseases indicating a strong potential demand for innovative therapies like PB-119 [3]. - The collaboration with PDC, a leading pharmaceutical research organization in the region, is expected to enhance the market entry and commercialization of PB-119 [3][4]. Group 3: Strategic Partnership - PDC will have exclusive rights to develop, register, produce, distribute, market, and commercialize PB-119 in the Middle East and Africa, including comprehensive technology transfer and local production [2][3]. - The partnership reflects Paig Bio's strong R&D capabilities and the promising clinical performance of PB-119, further solidifying its position in the metabolic disease sector [4].

以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖已成为癌症的重要诱因，目前已知有超过13种癌症的发生与肥胖密切相关。作为仅次于吸烟的第二大可预防癌症风险因素，肥胖的危害不 容忽视。 然而，科学家们却发现一个令人困惑的现象：尽管肥胖会加速癌症的发生和进展，但在接受免疫治疗时，肥胖患者却往往表现出"保护效 应"——高BMI人群对免疫疗法的响应率更高，生存预后也更理想。 这究竟是肥胖隐藏的"善意"，还是背后藏着不为人知的机制？ 近日，范德堡大学的科研团队在《自然》杂志上发表了最新研究。他们发现，肥胖引发的炎性细胞因子会刺激肿瘤相关巨噬细胞（TAM）上 PD-1的表达，削弱了机体对肿瘤的免疫监视能力。虽然这种机制助推了癌症的发展，但同时也让抗PD-1免疫疗法有了更大的施展空间。 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。 研究人员将小鼠分为两组，分别喂以低脂饮食（LFD，脂肪提供10%的能量）和高脂饮食（HFD，脂肪占比高达45%），喂食周期从6周龄 ...