Core Viewpoint - The article discusses the urgent need for new mechanisms in obesity treatment, highlighting the development of a novel siRNA candidate drug, SGB-7342, by Shengyin Biotech, which targets INHBE for obesity treatment [4][11]. Group 1: Obesity as a Public Health Challenge - Obesity is a chronic metabolic disease characterized by abnormal or excessive fat accumulation, significantly increasing the risk of cardiovascular diseases, type 2 diabetes, and various cancers [5]. - The global population of obese individuals has surpassed 1 billion and is expected to reach approximately 1.37 billion by 2035; in China, there are about 180 million adult obesity patients [6]. Group 2: Current Treatment Limitations - Current mainstream obesity treatments primarily involve GLP-1 receptor agonists, which suppress appetite through the central nervous system but have drawbacks such as gastrointestinal side effects, muscle loss risk, and weight regain after discontinuation [7]. Group 3: RNAi Therapy as a New Approach - RNAi therapy offers a differentiated treatment strategy that does not rely on central appetite regulation, aiming to regulate fat metabolism at the source by targeting key genes involved in fat breakdown and storage [8]. - This approach is expected to selectively reduce fat while preserving muscle mass and improving overall metabolic health, potentially lowering the risk of adverse effects associated with traditional therapies [8]. Group 4: INHBE as a Novel Metabolic Target - The INHBE gene, primarily expressed in the liver, encodes the secreted protein Activin E, which regulates fat breakdown and energy storage by binding to the ALK7 receptor in adipose tissue [9]. - Genetic studies indicate that individuals with INHBE loss-of-function mutations exhibit favorable metabolic traits, providing a biological basis for targeting INHBE in drug development [9]. Group 5: SGB-7342 Candidate Drug - SGB-7342 is a siRNA candidate drug targeting INHBE for obesity treatment, utilizing Shengyin Biotech's proprietary GalNAc conjugation delivery technology for precise liver targeting [10]. - The mechanism involves silencing INHBE mRNA in the liver to lower Activin E protein levels, promoting fat breakdown without inducing muscle loss, thereby improving metabolic disorders and insulin resistance [10]. - Preclinical studies show that SGB-7342 leads to significant weight loss and improved body composition while maintaining muscle mass, demonstrating good safety and tolerability [10]. Group 6: Future Outlook - Obesity is recognized as a complex systemic metabolic disease rather than merely a weight issue, with significant unmet clinical needs in the global obesity treatment landscape [11]. - RNAi therapy, with its novel mechanism directly targeting metabolic pathways, is expected to offer differentiated advantages in selective fat reduction, muscle protection, and long-lasting treatment [11].

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。 肥胖不仅是一种身体特征，更被医学界认定为一种疾病。世界卫生组织已将肥胖列为全球十大慢性疾病之一。大量研究证实，肥胖人群更容易 患上代谢综合征、心脑血管疾病、慢性肾病，甚至还是多种癌症的重要风险因素。 在中国，超重和肥胖人数占总人口的49%。虽然中国的肥胖率并非全球最高，但由于人口基数庞大，中国已成为全球肥胖人口最多的国家。 BMI（身体质量指数）是国际上通用的衡量体重是否健康的标准。计算公式为：BMI=体重÷身高的平方。中国成年人BMI标准为18.5-23.9， 超过24为超重，超过28即为肥胖。 目前，关于中国人群在成年早期（18-34岁）BMI与心血管疾病风险之间的关系，尚未有明确结论。2024年6月14日，北京大学余灿清团队在 《柳叶刀》子刊"Lancet Public Health"（影响因子50）发表了题为《成年早期BMI与心血管疾病：中国Kado ...

作用机制：多通路改善代谢与心血管功能 12月15日，华东医药披露，其在研 GLP-1R/GIPR 双靶点激动剂 HDM1005 的减重 II 期临床研究取得积极结果，显示出显著的减重疗 效及良好的安全性和耐受性。 整理 | GLP1减重宝典内容团队 HDM1005 注射液由华东医药子公司 中美华东 自主研发，拥有全球知识产权，属于 1 类创新化学药。该产品为多肽类 长效人源化 GLP-1R/GIPR 双重激动剂，具备同时调控食欲、体重与代谢的潜力。 临床前研究表明，HDM1005 通过同时激活 GLP-1R 与 GIPR，促进环磷酸腺苷（cAMP）生成，从而：增强胰岛素分泌，抑制食欲、 延缓胃排空，改善整体代谢功能。 研究结果显示，基于治疗策略分析（estimand）：0.5 mg、1.0 mg、2.0 mg、4.0 mg 组的22 周体重较基线分别下降7.47%、9.73%、 13.31% 和 13.28%，安慰剂组体重下降 2.46%； 在此基础上，HDM1005 还展现出改善血浆容量、降低氧化应激和全身炎症、提升心血管适应性等综合效应，具备 降糖、减重，并改善 MASH 及射血分数保留型心力衰竭（HFp ...

Core Viewpoint - Neurovalens has received FDA De Novo approval for its non-invasive weight management product, Modius Lean, which utilizes neurostimulation technology to aid in weight loss and body composition management [4][6][7]. Product Development - Modius Lean is designed to send gentle electrical pulses to the brain 60 minutes before sleep, helping to reduce visceral fat while maintaining lean body mass [6]. - The product has shown a clinically significant improvement, with a 13% average reduction in visceral fat over six months in a study involving 241 overweight and obese adults [6]. Market Strategy - With the De Novo approval, Neurovalens can now sell Modius Lean directly in the U.S. market with a prescription, marking a significant step in the company's long-term growth strategy [6][7]. - The company plans to expand its clinical research to include additional indications, having already submitted an application for PTSD [6]. Financial Background - Neurovalens has raised approximately £20 million (around $27 million), including an $8.1 million funding round completed earlier this year [6]. Industry Context - The CEO of Neurovalens highlighted that about three-quarters of adults in the U.S. are considered overweight or obese, indicating a growing market for low-risk, non-invasive treatment options like Modius Lean [7].

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。 《柳叶刀糖尿病和内分泌学子刊》最新发表的一项突破性Meta分析揭示了减重与糖尿病缓解之间的精确关联：在超重或肥胖的2型糖尿病患者 中，体重下降与疾病缓解呈现强劲的剂量反应关系。这一关键发现与患者年龄、性别、种族背景、病程长短、初始糖化血红蛋白水平、体重指 数或减重方式均无关联。 研究团队对PubMed、Embase和临床试验注册库中截至2024年7月30日的全部相关随机对照试验进行了系统筛查，最终精选出22项高质量研 究，包含29个完全缓解和33个部分缓解评估指标。研究采用严格标准：完全缓解定义为干预一年后糖化血红蛋白低于6.0%或空腹血糖低于 5.6mmol/L且不使用任何降糖药物；部分缓解则为糖化血红蛋白低于6.5%或空腹血糖低于7.0mmol/L且不使用降糖药物。 用 前 沿 科 学 理 解 肥 胖 Obesity World 界卫生组织 read ( ...

Core Viewpoint - The article emphasizes the importance of adhering to the recommended administration guidelines for oral semaglutide to achieve optimal therapeutic effects in weight loss and blood sugar control [12][14]. Administration Guidelines - The FDA recommends taking oral semaglutide before breakfast with no more than 4 ounces (approximately 120 milliliters) of water, followed by a minimum 30-minute wait before consuming breakfast or other medications [2]. - Taking the medication before any meal or after any meal is less effective due to shorter fasting periods compared to taking it before breakfast [3][5]. - If a person only eats lunch and dinner, taking the medication before lunch is acceptable; similarly, if only breakfast and dinner are consumed, taking it before dinner is also permissible [6]. Fasting and Water Intake - Longer fasting times before taking the medication result in higher plasma concentrations of semaglutide, leading to better clinical outcomes [5]. - Drinking excessive water to mask the bitterness of the pill is not advisable, as it may hinder the absorption of the active ingredient [9][10]. - It is crucial to wait at least 30 minutes after taking the medication before eating to avoid food interference with absorption [11]. Occasional Non-compliance - Missing a dose or occasionally not following the guidelines does not significantly impact overall efficacy, but consistent non-compliance can affect results [12][13]. Efficacy Comparison - Oral semaglutide (Rybelsus) and injectable semaglutide (Ozempic) are equally effective, with studies showing similar results in A1C reduction and weight loss among similar patient populations [15][17].

Core Insights - The article discusses the positive results of Eli Lilly's TRIUMPH-4 clinical trial, which evaluated the efficacy and safety of retatrutide in overweight or obese adults with knee osteoarthritis as an adjunct to diet and exercise [4][5]. Group 1: Clinical Trial Results - TRIUMPH-4 is a global study with 84% of participants having a baseline BMI ≥35 kg/m², showing significant weight loss and improvement in pain and physical function at 68 weeks [5][6]. - The average weight loss was 28.7% (approximately 71.2 pounds), and the knee pain score (WOMAC) decreased by up to 4.5 points, a reduction of 75.8% [6]. - Key secondary endpoints showed high rates of extreme weight loss: 47.7% for the 9 mg group and 58.6% for the 12 mg group achieving ≥25% weight loss, with nearly 40% in the 12 mg group achieving ≥30% weight loss [7]. Group 2: Cardiometabolic Benefits - Retatrutide also significantly improved various cardiovascular risk indicators, including non-HDL cholesterol, triglycerides, and high-sensitivity C-reactive protein (hsCRP), with an average systolic blood pressure reduction of 14 mmHg in the 12 mg group [8]. Group 3: Safety Profile - The safety profile of retatrutide is consistent with other GLP-1 receptor agonists, with common adverse events including nausea, diarrhea, constipation, vomiting, and decreased appetite, mostly mild to moderate [9]. - The overall discontinuation rate due to adverse events was similar between treatment and placebo groups, with a lower rate in the high-risk population (BMI ≥35) [9]. Group 4: Future Outlook - The TRIUMPH program has enrolled over 5,800 participants, with seven additional Phase III study results expected by 2026, including lower maintenance doses (4 mg) [11]. - Eli Lilly anticipates that retatrutide could become an important treatment option for patients requiring significant weight loss and suffering from multiple obesity-related complications [11].

Core Viewpoint - The brain-computer interface (BCI) industry is entering a rapid growth phase, with the global market expected to reach approximately $12.4 billion by 2034, reflecting a compound annual growth rate (CAGR) of 17.35% [4] Group 1: Market Overview - The BCI market is experiencing significant advancements due to the integration of technologies such as artificial intelligence, flexible materials, and biosensors [4] - Strong Brain Technology, one of the "Six Little Dragons" in Hangzhou, has completed a Pre-B round of financing, achieving a post-investment valuation exceeding $1.3 billion, positioning it as a leading unicorn in the domestic BCI sector [4][7] Group 2: Technological Directions - There are two main technological directions in the BCI field: invasive and non-invasive. Invasive technologies, represented by Neuralink, involve surgical implantation of electrodes, offering high signal quality but facing high costs and ethical concerns [5] - Non-invasive technologies, exemplified by Strong Brain Technology, do not require surgery and are more suitable for large-scale applications, primarily used in rehabilitation training and seen as having greater commercial potential [5] Group 3: Product Development and Controversies - Strong Brain Technology is developing a product akin to an "electronic version of semaglutide," aimed at reducing appetite to assist with weight loss, which has sparked discussions about the boundaries of consumer applications for BCI [7] - The company's product portfolio spans three main areas: smart bionics, smart health, and smart education, including devices like bionic hands and legs, sleep devices, and attention training systems [7] Group 4: Technological Accumulation - Strong Brain Technology has developed a proprietary solid-state gel electrode known as the "super sensor," capable of high-precision collection of brain and muscle electrical signals [8] - The company has secured over 460 authorized patents, with more than 250 core invention patents, placing it among the leaders in the global BCI industry [8]

Core Viewpoint - The article focuses on individuals who successfully lose weight through lifestyle changes but experience weight regain, highlighting the challenges of long-term obesity management and effective strategies to prevent weight rebound [7]. Summary by Sections Weight Regain Challenges - A systematic review and meta-analysis indicate that approximately 75% of individuals who lose an average of 14 kg through lifestyle interventions will regain weight within about 5 years [7]. - Weight rebound is not limited to those who undergo lifestyle changes; individuals who stop medication or have undergone weight loss surgery also face similar challenges [7]. Mechanisms Behind Weight Regain - A 2022 study found that macrophages in adipose tissue produce elevated levels of lipopolysaccharide-induced cytokines, contributing to a "fat memory" that increases the risk of weight regain [9]. - A 2023 study published in *Nature Metabolism* revealed that obese individuals have a diminished brain response to nutritional stimuli, which may be a key factor in weight rebound after weight loss [9]. Strategies to Reduce Weight Rebound Risk 1. **Dietary Adjustments** - High-protein, low glycemic index (GI), or low glycemic load diets can help reduce the risk of weight rebound. Anti-inflammatory dietary patterns are also recommended [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, and promotes fat oxidation, which aids in maintaining weight loss [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are suggested to prevent weight regain by reducing fat tissue mass [13]. 4. **Individualized Management and Ongoing Research** - Weight rebound is influenced by multiple factors, necessitating further scientific research to explore effective long-term management strategies tailored to different populations [14].

整理 | GLP1减重宝典内容团队 一种每日一次口服的减重药物，正被视为注射类GLP-1减肥药之外的更易获得选择。美国生物科技公司Syntis Bio近日宣布，已完成 3800万美元融资，用于加速其口服减重药的研发进程。该药物通过模拟胃旁路手术的生理效果，在不进行侵入性手术的情况下，帮助调 节食欲与代谢。 Syntis Bio总部位于波士顿，本轮融资中，公司完成了3300万美元A轮融资，资金将用于推进核心产品Synt-101的开发，同时还获得了 最高500万美元的非稀释性科研资助。 Synt-101是一款每日服用一次的口服制剂，其作用机制并非直接抑制食欲，而是暂时阻断小肠上段对营养的吸收，并将营养物质重新引 导至下段，从而激活人体自身释放调节饱腹感和代谢的激素反应。该产品基于公司自主研发的"Synt"合成组织内衬技术，通过类似贻贝 黏附机制的涂层，在小肠内形成可持续约24小时的功能性覆盖层。 尽管当前研发重点集中在减重领域，Syntis Bio认为，这一技术平台具备高度延展性，未来可应用于多种疾病治疗场景。 公司披露的临床前数据显示，在动物模型中，Synt-101实现了每周约1%的稳定体重下降，同时瘦体重保持 ...