整理 | GLP1减重宝典内容团队 Christina 并不是第一次尝试减肥。节食、运动，她都试过，体重也确实下降过，但最终总会反弹。尤其是在 2022 年生下儿子之后，体 重问题再次失控。 当以 Wegovy、Zepbound 为代表的 GLP-1 类减重药物出现时，她一度认为这可能是终极答案。这些药物以前所未有的效率帮助人们减 重，但现实很快泼了冷水——高昂的价格和保险不覆盖，让 Christina 无法长期负担。 在几乎没有其他选择的情况下，她报名参加了一项临床试验。试验保证她可以使用数月的明星减重药物，而在药物停止之后，还有一 个"额外选项"。 这个选项不是新的注射剂，也不是口服药，而是一种一次性的医疗器械介入。它不作用于大脑，也不直接改变胃容量，而是将目标锁定 在肠道本身——准确来说，是小肠上段的十二指肠，通过重塑其对营养和代谢信号的处理方式，帮助维持减重成果。 这项技术通过微创内镜完成，目的非常明确：为那些希望停用 GLP-1 药物的人，保住已经来之不易的体重下降效果，避免长期用药的 成本、注射负担和副作用。如果进展顺利，2026 年，这类设备有望首次获得监管批准并走向临床应用。 我们正在创造一个 ...

以下文章来源于AI医疗观察 ，作者关注AI医疗的 AI医疗观察 . 响应《关于深入实施"人工智能+"行动的意见》，推动AI在医疗领域的应用，本账号发布权威资讯 AI不仅能帮你减肥，竟然还能带来巨额收益！ 据报道，总部位于伦敦的Simple Life公司本月完成了3500万美元（约合2.5亿元人民币）的融资。更令人惊讶的是，它的盈利能力远超融资额 度：年收入高达1亿美元（约7亿元人民币），同比增长达到64%。 既然AI减肥如此赚钱，国内市场是否已经涌现大量模仿者？答案却出人意料——相关企业寥寥无几。 在国内，AI应用已火热发展两三年，为何这样一条高收益赛道却鲜有人涉足？本文将尝试分析背后的原因。 Simple Life的最大创新在于将科学减肥与AI深度融合，把原本枯燥的减肥过程变成了充满乐趣的"游戏化"体验。 公司CEO迈克·普里特科夫表示："我们正在把健康习惯变成一款充满激励的游戏，让用户不仅看到成果，还能与健康建立正向关系。" 具体来看，Simple Life的产品设计了以下机制： 1. 成就积分系统：平台会根据用户日常行为，比如拍照、打卡、称重等，智能计算"成功分数"，并实时更新"今日计划"。该分数基于同 ...

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。 近年来，减肥药物的快速发展正深刻改变医疗行业，不仅实现了持久的体重控制，还在心血管健康、血糖平衡以及血压和胆固醇管理方面展现 出显著益处。此次新研究为开发新靶点药物打开了大门，这些靶点未来既可单独应用，也能与现有减重药物联用，从而更有效地控制食欲。 体重受遗传和环境因素双重影响。Zhang博士指出，由于饮食和生活方式差异巨大，直接在人类中寻找导致肥胖的基因变异极具挑战。因此， 研究团队采用了AMM（自动减数分裂定位）增强的遗传学方法，以更好地解析肥胖的遗传基础。 AMM（Automated Meiotic Mapping）是一项结合遗传学与机器学习的新技术，能够高效定位导致特定表型的基因突变。该技术由UTSW团队 与诺贝尔奖获得者Bruce Beutler博士共同开发，通过分析基因型与表型数据，利用统计和人工智能手段，快速筛查出与性状相关的遗传变异。 为进一 ...

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 Rebound 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 Rebound - 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 successful 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, such as increased intake of olive oil, tomatoes, leafy greens, nuts, deep-sea fish, and fruits, while reducing refined carbohydrates, fried foods, sugary drinks, red meat, and margarine, may also lower rebound probabilities [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, increases satiety, promotes fat oxidation, and protects muscle mass, all of which help maintain weight loss. Higher levels of physical activity correlate with better weight maintenance outcomes [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are recommended to prevent weight rebound, such as reducing adipose tissue mass for more stable weight control [13]. 4. **Individualized Management and Ongoing Research** - Weight rebound is influenced by multiple factors, including diet, exercise, medication, and biomedical interventions. Future research should focus on different populations to explore more effective long-term management strategies [14].

整理 | GLP1减重宝典内容团队 一条极具诱惑力、也极其艰难的技术路线 ORMD-0801 最大的亮点，在于它试图解决一个全球医学界长期未解的难题：让胰岛素实现真正的口服给药。相较注射制剂，口服形式 在患者依从性、长期用药体验上具有天然优势。 从需求端看，全球糖尿病患者规模庞大，胰岛素市场本身就具有足够吸引力。更关键的是，在口服降糖药中，绝大多数药物依赖患者自 身残存的胰岛β细胞功能来促进胰岛素分泌。对于病程较长、胰岛功能几乎耗竭的2型糖尿病患者而言，外源性胰岛素几乎是唯一选择。 但长期注射所带来的依从性问题、安全性隐患，也正是口服胰岛素被寄予厚望的根本原因。这一逻辑，并非天汇生物独有，而是整个行 业的共同判断。 12月29日，国家药监局官网一则并不起眼的通知，引发了业内对口服胰岛素命运的再度关注。合肥天汇生物申报的重组人胰岛素肠溶胶 囊 ORMD-0801 出现在当日药品通知件送达信息中，意味着这款备受期待的创新药未能获得批准。 次日，天汇生物方面回应称，此次注册申请终止为公司主动撤回，是整体战略调整的一部分。但在医药产业看来，这一结果并非单一企 业的取舍，而是再次凸显了口服胰岛素这一"高难度赛道"的长期 ...

Core Insights - The article emphasizes the shift in comprehensive health management from human decision-making to system-driven execution, highlighting the importance of products that take on greater responsibility for health outcomes [4][22]. Group 1: Execution Responsibility in Health Management - Traditional health management applications rely on users to record data and follow suggestions, often failing during the transition from advice to action [5]. - Newer products are designed to automate measurement, triggering, and intervention, thereby increasing the system's responsibility for health outcomes [5][22]. - WELT exemplifies this by focusing on waist circumference as a key health metric, integrating sensors to track changes and provide actionable feedback without user input [6][8]. Group 2: Innovative Product Examples - ElliQ integrates health management into the daily routines of elderly users, actively engaging them and their caregivers through reminders and updates, thus expanding execution responsibility to the family network [10][12]. - UREVO automates training plans within its device usage, reducing the need for user decision-making and making health behaviors a default part of device interaction [13][15]. - Appscent Medical and Vagustim explore non-traditional interaction methods to lower execution costs, with Appscent using olfactory stimulation during sleep to assist recovery [19][21]. Group 3: Market Trends and Future Directions - The article suggests that the future of comprehensive health management lies in creating replicable execution Standard Operating Procedures (SOPs) that automate measurement, triggering, and intervention [22]. - Companies like WELT, ElliQ, and UREVO are leading the way by embedding health management into everyday actions, moving from mere health information products to comprehensive health execution systems [22].

Core Viewpoint - GLP-1 agonists, such as semaglutide and tirzepatide, are popular weight loss medications, but a significant number of users discontinue their use within a year due to various factors, including cost, side effects, and prescription limitations [5][7]. Group 1: Usage and Effects of GLP-1 Agonists - In 2021, approximately two-thirds of individuals in the U.S. who started using GLP-1 agonists stopped within a year [5]. - The World Health Organization estimates that over 1 billion people are currently obese, representing one-eighth of the global population [7]. - Studies indicate that when individuals stop using GLP-1 agonists, many regain some weight, as the body naturally attempts to maintain its set weight [10]. Group 2: Weight Loss Outcomes - In a study involving around 800 participants, those who injected semaglutide weekly lost an average of 10.6% of their body weight over four months, but one-third of those who switched to a placebo regained nearly 7% of their weight after 11 months [12]. - Another trial showed that participants lost an average of 17.3% of their weight after more than a year of treatment, but about two-thirds of this weight was regained after one year without clinical intervention [12]. - An observational study found that 44% of individuals who lost at least 2.3 kg and then stopped semaglutide regained at least 25% of their weight within a year [12]. Group 3: Health Risks Associated with Discontinuation - Discontinuation of semaglutide not only leads to weight regain but also results in the rebound of health risk factors such as blood pressure, blood sugar, and cholesterol levels [13]. - Patients who had been on semaglutide for over four months showed a decrease in waist circumference, but those who switched to a placebo began to regain abdominal fat, which is linked to health issues like fatty liver disease [12][13]. Group 4: Recommendations for Discontinuation - It is suggested that individuals gradually reduce their dosage of GLP-1 agonists rather than stopping abruptly to mitigate rebound hunger [14]. - Continuous monitoring of appetite and weight is recommended for those who voluntarily stop medication, with a suggestion to resume medication if weight increases by 5 pounds (2.5 kg) [14]. - For those who must stop using GLP-1 agonists, maintaining dietary changes, exercise, and psychological counseling is essential [15]. Group 5: Optimal Dosing Strategies - Research presented at the European Obesity Congress indicated that starting patients on the lowest effective dose of anti-obesity medications can lead to significant weight loss while minimizing side effects [17]. - In a study of 2,246 individuals, those on a weight management program lost an average of 14.9 kg over 76 weeks, with the average maximum dose of semaglutide being 0.77 mg [17]. - Another study demonstrated that a weekly dose of 0.5 mg of semaglutide resulted in an approximate 11% weight loss in patients with a BMI over 30 [19].

过去一年，对诺和诺德来说并不轻松。股价大幅回撤、百年历史上最大规模的管理层调整、资本市场情绪急转直下，这家丹麦制药巨头 正站在聚光灯下，被反复拷问一个问题：它是否还能把 GLP-1 的科学领先，转化为可持续的商业回报？ 在投资者眼中，答案似乎越来越悲观。随着礼来等强劲对手入场、仿制药和复合制剂扩散，减重药这一曾经的"黄金赛道"开始显露出竞 争红海的轮廓。但在科研界，情绪却几乎完全相反——科学家们普遍认为，GLP-1 的潜力远未被完全释放。 最初，人们关注的是这类药物在控制体重、改善血糖以及降低心血管风险方面的价值。而如今，研究的边界正在被不断推远，新的焦点 逐渐转向一个更复杂、也更具想象空间的领域：大脑。 整理 | GLP1减重宝典内容团队 从降糖药到"系统性调节器" 司美格鲁肽，也就是人们熟知的 Ozempic 和 Wegovy，最早被开发用于治疗 2 型糖尿病。随着其显著的抑制食欲和减重效果被发现， 大规模"超适应症使用"迅速蔓延，并最终推动其正式获批用于肥胖治疗，成为诺和诺德每年贡献数十亿美元收入的核心产品。 但故事并未止步于此。监管机构和学术界正陆续确认，这类药物在多个系统性疾病中展现出额外获益。司美 ...

Core Viewpoint - The article discusses the approval of SYH2069 injection by the National Medical Products Administration of China for clinical trials, marking it as a potential first-in-class GLP-1/GIP receptor dual agonist in China, which shows promising weight loss and metabolic improvement effects [6][7]. Group 1: Product Development - SYH2069 injection has received approval for clinical trials in both China and the United States, indicating its potential for significant market entry [6]. - The product selectively activates the cAMP pathway, significantly reducing β-arrestin recruitment, which enhances drug efficacy and duration of effect [7]. - In studies involving diet-induced obesity mice and non-human primates, SYH2069 demonstrated superior weight loss and metabolic improvement compared to existing products [7]. Group 2: Safety and Efficacy - Toxicology studies in non-human primates showed good tolerance for SYH2069, with no observed vomiting or gastrointestinal adverse reactions [7]. - The product is expected to be a new generation therapy for overweight/obesity and other metabolic diseases, with a clinical indication for weight management in individuals with obesity or overweight and at least one weight-related comorbidity [7]. Group 3: Clinical Value - SYH2069 also has potential for improving blood glucose control in adults with type 2 diabetes (T2DM), indicating high clinical development value [7].

Core Viewpoint - The article discusses the rising obesity rates in China and the global implications of obesity, highlighting the transformative role of GLP-1 medications like semaglutide in the weight loss market, while also addressing the challenges of medication adherence and the reasons for discontinuation of use [4][6][20]. Group 1: Obesity Statistics and Economic Impact - China has the highest number of overweight and obese individuals globally, with over 530 million adults affected, including approximately 100 million classified as obese [4] - By 2030, it is projected that the number of overweight adults in China will reach 540 million, and the number of obese individuals will increase to 150 million, representing a 2.8-fold and 7.5-fold increase from 2000, respectively [4] - The global obesity rate is expected to rise to 25% by 2035, up from 14% in 2020, with obesity impacting global economic productivity equivalent to 3.6% of the US GDP, leading to indirect costs as high as $1.24 trillion [4] Group 2: Medication Adherence and Discontinuation - A study published in the journal "Obesity" found that semaglutide has the highest adherence rate among weight loss medications, with 63% of users still on the medication after three months, 56% after six months, and 40% after one year [6] - Common side effects of GLP-1 medications include nausea, diarrhea, and vomiting, which may lead to discontinuation; 17% of patients reported nausea even at low doses of semaglutide [9] - Supply issues have plagued semaglutide since 2022, contributing to challenges in patient adherence [10] Group 3: Effects of Discontinuation - A clinical trial indicated that participants who stopped semaglutide after an initial 20-week treatment regained an average of 6.9% of their body weight, while those who continued the medication lost an additional 7.9% [7] - Participants who maintained semaglutide use and lifestyle changes lost an average of 17.3% of their body weight over 68 weeks, while those who stopped regained about two-thirds of their weight [7] Group 4: Reasons for Stopping Medication - Patients may stop using semaglutide after reaching their target weight or due to a plateau in weight loss, mistakenly believing the medication is no longer effective [12][15] - Gradual dose reduction is recommended to mitigate increased hunger sensations that may occur after stopping the medication [15] Group 5: Importance of Lifestyle Changes - Effective weight loss requires a combination of medication and lifestyle changes; reliance solely on medication is insufficient [16] - Regular exercise is crucial for preventing weight regain and improving overall health [19] Group 6: Long-term Use of Semaglutide - Studies show that continuous use of semaglutide over two years can lead to a weight reduction of 15.2% compared to placebo, with 77.1% of patients losing at least 5% of their body weight [20] - Obesity is a chronic condition requiring ongoing management, similar to other chronic diseases, emphasizing the need for long-term medication use [21]