整理 | GLP1减重宝典内容团队 ▍减肥平台期"防不胜防" 最终服用 GLP-1 的人趋于达到平台期（plateaus）。 什么是平台期？ 平台期是导致每一次治疗或行为的改变最终都会停滞不前的一种自我保护 机制。 平台期无法避免 ，处于减肥平台期的人们即使仍然携带多余的脂肪，似乎也无法减轻体重。这不应该令人惊讶，因为 平台期通常发生 在所有减肥干预措施中 ，无论是饮食、手术还是减肥药物。 为什么会存在平台期？ 平台期不是意志力的问题，它与 脑化学和新陈代谢密切相关 。大脑分泌饥饿荷尔蒙，用来抵抗卡路里限制，同时新陈 代谢减慢，使得燃烧的卡路里更少。 因此 设定患者的期望很重要 。医生应该在治疗开始时教育他们的患者，没有干预是"万能的"，他们仍然必须采用 健康的饮食和积极的生活方 式 才能做出持久的改变。 ▍改变生活方式 得到 注册营养师和健康教练的个性化支持 ，远比尝试许多时尚饮食来得有用。事实上，GLP-1 仅在用作行为矫正的辅助手段时被 FDA 批准用 于减肥。 注册营养师 可以帮助患者在服药期间处理副作用并预防营养不良，并提供医学营养疗法，帮助人们以健康、可持续的方式减肥。比如 应避免食用油条、浓奶油 ...

Core Viewpoint - Hims & Hers Health is redefining healthcare delivery by focusing on consumer relationships and subscription-based services rather than traditional one-time medical consultations [5][11]. Company Overview - Hims & Hers Health, founded in 2017 and headquartered in San Francisco, is a publicly traded company centered on DTC digital healthcare, initially addressing male health issues like erectile dysfunction and hair loss through online consultations and direct medication delivery [6][8]. Business Structure - The user journey is standardized, where users complete health questionnaires online, receive prescriptions after review, and have medications delivered, primarily through cash payments, minimizing reliance on insurance [9]. - Hims views telehealth as a subscription service for chronic health needs, focusing on long-term relationships rather than one-time visits, leading to predictable cash flow and higher customer lifetime value [11]. Product Selection Capability - Hims' success is attributed to its clear and validated product selection criteria, focusing on long-term demand, manageable medical risks, and high consumer sensitivity to privacy and convenience [12][14]. - The company has introduced new product categories, particularly in weight management, integrating them into existing subscription models to foster long-term service relationships [14]. AI Integration in Business - AI is embedded in Hims' operations for user onboarding, service scheduling, and long-term management, enhancing decision-making based on user health data rather than replacing medical professionals [15][17]. - AI aids in structuring user interactions, analyzing behavior data, and optimizing product offerings, creating a data-driven cycle for service and product iteration [17]. Competitive Advantage - Hims' competitive edge stems from a multi-layered approach, including a deep understanding of compliance, data accumulation from subscription relationships, and establishing itself as a health management entry point for users [18][20].

整理 | GLP1减重宝典内容团队 欧洲减重药物市场迎来重要进展。欧洲药品管理局人用药品委员会已对更高剂量的Wegovy给出积极意见，推荐批准司美格鲁肽7.2 mg新剂量在 欧盟上市。这一决定，意味着肥胖症患者有望获得比现有方案更强效的药物选择，也标志着GLP-1减重治疗正式迈入"20%以上减重"的新阶 段。 从核心数据来看，在STEP UP研究中，不伴2型糖尿病的肥胖症患者接受司美格鲁肽7.2 mg治疗72周后，平均体重下降20.7%。更具突破性的 是，约三分之一的患者体重降幅达到或超过25%。这一结果明显高于当前广泛使用的2.4 mg剂量，显示出更高剂量在重度减重需求人群中的潜 力。 更高效的减重并未以牺牲安全性为代价。研究显示，司美格鲁肽7.2 mg的安全性和耐受性与已获批的2.4 mg剂量总体一致。体成分分析表明， 约84%的体重下降来自脂肪量减少，肌肉功能得以维持，这一结果缓解了外界对"快速减重可能导致肌肉流失"的担忧。 在临床价值层面，新剂量并非只关注体重本身。现有证据进一步巩固了Wegovy在改善肥胖相关并发症方面的综合获益，包括降低主要心血管事 件风险，如心肌梗死和脑卒中，以及减轻膝骨关节炎相 ...

Core Viewpoint - The article discusses the successful results of the phase III clinical trial (EECOH-1) for Enoglutide injection, a GLP-1 receptor agonist developed by Xianweida Biotech, which shows significant benefits in lowering blood sugar and weight in adults with type 2 diabetes [4][7]. Group 1: Clinical Trial Results - The EECOH-1 study involved 211 adult participants with poorly controlled blood sugar after dietary and exercise interventions, conducted across 32 centers in China [7]. - Participants were randomly assigned to receive either Enoglutide injection at doses of 0.6mg or 1.2mg, or a placebo, for 24 weeks, followed by an additional 28 weeks of treatment for the placebo group [7]. - After 24 weeks, both doses of Enoglutide significantly reduced HbA1c levels compared to the placebo, with the 1.2mg group achieving a reduction of 2.43% [7]. Group 2: Efficacy and Safety - The proportion of patients achieving HbA1c levels below 7.0% was significantly higher in the Enoglutide groups, with the 1.2mg group reaching 80.3% [7]. - Enoglutide also led to significant weight loss, with reductions of 4.51% and 4.74% for the 0.6mg and 1.2mg groups, respectively, after 24 weeks [8]. - The treatment improved various cardiovascular metabolic risk indicators and showed good overall safety and tolerability, with most adverse events being mild to moderate [8].

Core Insights - The article discusses the challenges faced by millions who stop using GLP-1 weight loss drugs due to side effects, high costs, or supply issues, and highlights emerging alternatives for weight management [11][12]. Group 1: Demand for Alternatives Due to GLP-1 Drug Discontinuation - GLP-1 drugs like Semaglutide (Ozempic, Wegovy) and Tirzepatide (Zepbound) have a high discontinuation rate of 37% to 81% within the first year, prompting patients to seek sustainable alternatives [12]. - Factors such as unstable drug supply, annual costs averaging tens of thousands of dollars, and side effects like nausea are driving patients towards traditional weight loss methods [12]. - The popularity of GLP-1 drugs has led to renewed interest in traditional weight loss methods, creating a new treatment paradigm of "drug initiation followed by diverse follow-up" [12]. Group 2: Innovations in Surgical and Endoscopic Techniques - Traditional weight loss surgeries, such as gastric bypass and sleeve gastrectomy, have been shown to achieve long-term weight loss of 30% to 50%, but global surgical penetration remains below 1% due to patient concerns about surgical trauma [13]. - The 2022 international guidelines lowered the BMI threshold for surgery, and institutions like the Mayo Clinic are exploring "drug-surgery sequential treatment" to enhance weight loss outcomes [13]. - Endoscopic techniques are gaining attention, including Endoscopic Sleeve Gastroplasty (ESG) and Gastric Mucosal Ablation (GMA), which are less invasive and have shown promising results [14][15]. Group 3: Challenges in Popularization and Payment Systems - Despite the potential of endoscopic techniques, their global adoption faces challenges such as limited insurance coverage and the need for standardized operational techniques [16]. - The average out-of-pocket cost for ESG is around $6,000, and GMA is not yet covered by insurance [16]. - Establishing multidisciplinary weight management centers is being promoted in countries like Brazil to integrate drug, endoscopic, and surgical resources, enhancing overall treatment quality [16].

整理 | GLP1减重宝典内容团队 一篇发表在权威 国际综合性医学期刊 JAMA（Journal of the American Medical Association）上名为《Is Weight Loss–Induced Muscle Mass Loss Clinically Relevant》的研究论文显示，服用胰高血糖素样肽 1 (GLP-1) 受体激动剂（如司美格鲁肽、替尔泊肽）的患者以及 治疗他们的医生 不必担心服用这些药物时通常会伴随体重快速下降而出现的肌肉过度流失。 研究表明，司美格鲁肽使得瘦体重占总体重的比例增加，导致个体在相对较轻的体重下拥有更高的肌肉质量和潜在的能量消耗能力。这 种变化可能会使个体在进行日常活动和体育锻炼时感到更加有力和健康。 ▍ 研究表明，关于司美格鲁肽等GLP-1 类减肥药物在降糖减重的同时还会改善身体机能 GLP-1 药物的受欢迎程度呈指数级增长，患者报告称，在已知具有心血管益处的情况下，其体重迅速下降了 25% 。 在线同步发表于《JAMA》上的论文中， Caterina Conte 医学博士、哲学博士（意大利圣拉斐尔罗马开放大学）、Kevin D. Hall 哲学 ...

Core Viewpoint - Eli Lilly has initiated a Phase III clinical trial for Brenipatide, a dual GLP-1 and GIP receptor agonist, in adult depression patients, marking a significant expansion of GLP-1 drug applications beyond metabolic diseases into central nervous system disorders [4][5]. Group 1: Clinical Development - The RENEW-MDD-1 study aims to evaluate the efficacy and safety of Brenipatide as an adjunct therapy compared to placebo in delaying disease relapse in adults with depression, with approximately 1,000 participants globally, including 90 from China [4]. - Brenipatide is the first GLP-1 class product to enter Phase III clinical trials for depression, indicating a pioneering step in this therapeutic area [5]. Group 2: Market Context - Eli Lilly's commercial success with its core product, Tirzepatide, which achieved sales of $24.8 billion in the first three quarters of 2025, growing 125% year-over-year, supports the potential for Brenipatide's cross-indication expansion [6]. - The company is strategically broadening the potential value of the GLP-1/GIP mechanism, exploring applications in addiction, mental health, and inflammation-related diseases, beyond just glucose control and weight loss [6]. Group 3: Broader Implications - The entry of Brenipatide into the depression treatment space signifies a critical transition for GLP-1 drugs, potentially reshaping their disease landscape and offering a new biological pathway for depression treatment [7]. - If the clinical trial demonstrates clinical value in relapse prevention, it could represent a pivotal shift for GLP-1 drugs from metabolic-focused therapies to a more versatile platform molecule [7].

Core Viewpoint - The article emphasizes the importance of maintaining a balanced and nutritious diet for individuals using GLP-1 medications for weight loss, highlighting that even with reduced food intake, nutritional needs must be met to avoid health issues [5][6][7]. Dietary Guidelines - New dietary guidelines suggest that women taking weight loss medications should consume between 1,200 to 1,500 calories daily, while men should aim for 1,500 to 1,800 calories [11]. - Recommended protein intake is over 60 to 70 grams per day, with sources including legumes, seafood, lean meats, poultry, low-fat dairy, and eggs [11]. - Healthy carbohydrates should make up 45% to 65% of total energy intake, with added sugars limited to below 10%. Suggested sources include whole grains, nuts, seeds, fruits, vegetables, and dairy [12]. - Fat intake should account for 20% to 35% of energy, with saturated fats limited to below 10%. Recommended fats include nuts, seeds, avocados, plant oils, and fatty fish, while fried and high-fat foods should be avoided due to gastrointestinal side effects from the medications [12]. - Daily fiber intake recommendations are approximately 21 to 25 grams for women and 30 to 38 grams for men, with fruits, vegetables, and whole grains as primary sources. Fiber supplements can be used if dietary intake is insufficient [12]. - Individuals are advised to consume two to three liters of fluids daily, including water, low-calorie beverages, and low-fat dairy, while limiting or avoiding caffeine [13]. - The guidelines also recommend supplementation of multivitamins, calcium, and minerals to ensure adequate micronutrient intake [14]. Monitoring and Professional Guidance - It is recommended that healthcare professionals or nutritionists monitor the dietary intake of patients using weight loss medications to prevent nutritional deficiencies [15]. - The necessity of thorough nutritional assessments before and during treatment with weight loss medications is emphasized, as many patients may require detailed guidance on what and how much to eat to ensure optimal dietary quality and avoid muscle loss [16].

Core Viewpoint - Australia is at the forefront of obesity research, with recent breakthroughs from the University of Melbourne potentially addressing obesity challenges [6][10]. Group 1: Research Breakthroughs - Researchers at the University of Melbourne have discovered three distinct types of adipocyte progenitor cells, challenging the long-held belief that there is only one type [10]. - The first type of cell leads to unconditional fat accumulation around organs, contributing to metabolic diseases like fatty liver [11]. - The second type, known as "fast-burning fat cells," can suppress weight gain and efficiently burn body fat, representing a significant focus for weight loss and health management [13]. - The third type functions to balance fat within the body, maintaining a stable state [14]. Group 2: Obesity Statistics in Australia - Australia has one of the highest obesity rates globally, with 70% of adults classified as overweight or obese, and one in five children also affected [16][17]. - The obesity issue has prompted ongoing scientific interest and research in Australia, with significant public engagement in weight loss advancements [17]. Group 3: Genetic Factors in Obesity - A recent study indicates that body shape is largely determined by genetics, with findings suggesting that infants with larger heads are more likely to become overweight as adults [24]. - Key brain regions, the nucleus accumbens and the medial orbitofrontal cortex, are linked to body fat content, with larger sizes in these areas correlating with higher fat levels [27]. - The nucleus accumbens is associated with pleasure and desire, while the medial orbitofrontal cortex relates to reward mechanisms and emotional regulation, impacting individuals' ability to resist food cravings [29].

Core Viewpoint - Roche's investigational dual-target GLP-1/GIP receptor agonist CT-388 has shown significant weight loss efficacy and safety in treating obesity, paving the way for further clinical development [4][6]. Group 1: Clinical Trial Results - The Phase 2 trial CT388-103 included 469 participants and evaluated three dosage levels of CT-388, with a maximum dose of 24mg administered weekly for 48 weeks [6]. - In the highest dose group, the average weight loss after 48 weeks was 22.5% after placebo correction, with a significant statistical difference, and no noticeable weight loss plateau was observed throughout the treatment [6]. - 95.7% of participants in the 24mg group lost at least 5% of their body weight, 87% lost at least 10%, and 47.8% lost at least 20%, with 26.1% losing over 30% [6]. - 54% of participants achieved obesity remission, with a BMI below 30 kg/m², compared to only 13% in the placebo group [6]. - Among prediabetic participants, 73% normalized their blood sugar levels after treatment with 24mg CT-388, while only 7.5% in the placebo group did so [6]. Group 2: Safety and Tolerability - CT-388's safety profile aligns with existing GLP-1 class drugs, with no new or unexpected safety signals reported [8]. - Adverse events were primarily gastrointestinal and mostly mild to moderate, with a discontinuation rate due to adverse events of 5.9% in the CT-388 group and 1.3% in the placebo group, indicating an acceptable range for similar drugs [8]. Group 3: Development Strategy - Roche has prioritized CT-388 as a key asset in obesity treatment, with ongoing Phase 2 trial CT388-104 assessing its efficacy and safety in obese patients with type 2 diabetes [9]. - Phase 3 clinical projects Enith1 and Enith2 targeting obesity alone are expected to start this quarter, marking a critical validation phase for the molecule [9]. - Roche plans to explore combination therapy with petrelintide alongside CT-388 to enhance its weight management efficacy and create a differentiated obesity treatment regimen [9]. Group 4: Mechanism of Action - CT-388 is a weekly subcutaneous injection dual receptor agonist that activates both GLP-1 and GIP pathways, suppressing appetite, regulating blood sugar, and improving overall energy homeostasis [9]. - The design employs biased signaling to achieve strong receptor activation while minimizing β-arrestin recruitment, reducing receptor internalization and desensitization risks, which may help prolong drug action and maintain long-term efficacy [9].