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。 近日，《自然》（Nature）旗下期刊Nature Reviews Endocrinology发布了一篇重磅综述，深入解析了影响体重反弹的多种潜在生物学机制。 这篇综述聚焦于那些通过调整生活方式成功减重后又出现体重反弹的人群，并探讨了多种预防体重回升的有效策略。文章指出，虽然通过改善 饮食结构或增加运动量等方式能够实现体重下降，但减重后体重反弹依然是长期管理肥胖的最大难题之一。 一项系统性回顾和meta分析（整合多项观察性研究数据）显示，依靠生活方式干预平均减重约14公斤的受试者中，约有75%的人会在5年左右 出现体重回升。 综述还强调，体重反弹并非仅限于生活方式干预人群，接受减肥手术或药物治疗后停药的人也常面临体重反弹的困扰。更有意思的是，减重后 体重反弹的情况在不同个体间差异巨大：有些人可以多年维持减重成果，而另一些人则在几个月内就恢复到原来的体重。深入 ...

整理 | GLP1减重宝典内容团队 世界卫生组织（WHO）近日正式发布《成人肥胖人群使用 GLP-1 类疗法的适应证与应用指南》，这是全球首个由WHO层面系统评估并规范 GLP-1 药物在肥胖管理中定位的权威文件。 该指南并非单纯"为减肥药背书"，而是在将肥胖明确界定为一种慢性、复发性疾病的前提下，试图回答一个更复杂的问题：在全球不同卫生体 系、资源条件和公平性约束下，GLP-1 药物应如何被"负责任地"使用。 从方法论出发：WHO如何制定这份指南？ 自2009年以来，WHO不断升级其指南制定流程，以确保科学严谨、程序透明、具备全球适用性。本次指南延续了 GRADE（证据分级与推荐强 度评估）方法学，不仅评估疗效证据本身，还系统纳入：患者价值与偏好，可行性与成本，卫生系统承载能力，公平性与可及性影响。 指南由多学科专家组成的 指南制定小组（GDG） 完成，成员涵盖肥胖医学、流行病学、临床药理、卫生经济学、公共卫生政策等领域，并首 次系统纳入肥胖患者的真实生活经验，以避免"技术理性"脱离现实。 肥胖被正式定义为"需要终身管理的慢性病" 点击关注，追踪最新GLP-1资讯 WHO在指南中反复强调：肥胖不是短期生活方 ...

Core Viewpoint - The article discusses the use of GLP-1 receptor agonists, particularly semaglutide, for weight management and the implications of pausing medication, emphasizing the importance of gradual dosage reduction to mitigate hunger rebound effects [4][12][14]. Group 1: Medication Effects and Timeline - After subcutaneous injection, semaglutide is absorbed into the bloodstream within 1-2 hours [8] - Peak concentration in the blood occurs within 24-48 hours, where the drug actively binds to GLP-1 receptors [9] - Noticeable effects, such as reduced appetite and improved blood sugar regulation, may begin within 1-2 weeks [10] - Steady-state levels are achieved after 4-5 weeks of weekly injections, leading to more pronounced appetite suppression and accelerated weight loss [11] Group 2: Discontinuation Strategies - It is recommended to start with the lowest dose and gradually increase to minimize side effects [12] - Gradual dose reduction is preferred over abrupt cessation to avoid increased hunger [14] - Monitoring appetite and weight changes is crucial for those planning to stop medication, with a focus on maintaining healthy eating and exercise habits [14] Group 3: Post-Discontinuation Outcomes - A 2021 clinical trial showed that participants lost an average of 10.6% of their weight during 20 weeks of semaglutide treatment, but those switched to a placebo regained an average of 6.9% of their weight [15] - An observational study indicated that 18% of patients regained their lost weight after one year off the medication, while 26% regained more than 25% of their lost weight [15] Group 4: Importance of Continued Medication - The STEP 5 trial demonstrated that continuous use of semaglutide for 2 years resulted in a 15.2% weight loss compared to placebo [18] - In the SELECT trial, patients maintained an average weight loss of about 10% over 4 years, highlighting the chronic nature of obesity and the need for long-term management [18] Group 5: Obesity as a Chronic Disease - Recent studies confirm obesity as a chronic disease, with 76.8% of patients and 94.6% of doctors agreeing on its classification [19] - Obesity is linked to various health issues, including type 2 diabetes and cardiovascular diseases, necessitating its inclusion in chronic disease management [19] Group 6: Weight Loss and Health Improvement - Weight loss of 5% can improve hypertension and blood sugar levels, while a 10-15% reduction significantly lowers risks of cardiovascular diseases and diabetes [21] - Greater weight loss (over 15%) can effectively alleviate type 2 diabetes symptoms and improve overall health outcomes [21]

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。 肥胖世界 Obesity World 《肥胖世界》(Obesity World)关注电子杂 志官方账号,用前沿科学理解肥胖 www.obesityworld.cn Obesity World 用 前 沿 科 学 理 解 肥 胖 | nature | | | | | --- | --- | --- | --- | | Explore content ✓ | About the journal ✓ | Publish with us > | Subscribe | | nature > news feature > article | | | | NEWS FEATURE | 11 June 2025 How to keep weight off after obesity drugs Options are emerging for the tens of m ...

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].

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。 近日，《自然》（Nature）旗下期刊Nature Reviews Endocrinology发布了一篇重磅综述，深入解析了影响体重反弹的多种潜在生物学机制。 这篇综述聚焦于那些通过调整生活方式成功减重后又出现体重反弹的人群，并探讨了多种预防体重回升的有效策略。文章指出，虽然通过改善 饮食结构或增加运动量等方式能够实现体重下降，但减重后体重反弹依然是长期管理肥胖的最大难题之一。 一项系统性回顾和meta分析（整合多项观察性研究数据）显示，依靠生活方式干预平均减重约14公斤的受试者中，约有75%的人会在5年左右 出现体重回升。 综述还强调，体重反弹并非仅限于生活方式干预人群，接受减肥手术或药物治疗后停药的人也常面临体重反弹的困扰。更有意思的是，减重后 体重反弹的情况在不同个体间差异巨大：有些人可以多年维持减重成果，而另一些人则在几个月内就恢复到原来的体重。深入 ...

整理 | GLP1减重宝典内容团队 世界卫生组织近日首次发布面向成人肥胖管理的GLP-1药物指南，明确将GLP-1受体激动剂纳入长期综合治疗体系，并强调必须与行为 干预同时开展。这一信号标志着全球公共卫生体系正式将GLP-1从"创新药物"提升为"结构性治疗工具"，凸显肥胖作为慢性疾病的长期 治理需 求。 指南的推出背景，是肥胖已成为全球最紧迫的公共健康挑战之一。全球超过十亿人受到肥胖影响，而超重与肥胖相关疾病所引发的死亡 在全球非传染性疾病负担中占比不断上升。新的指南明确指出，肥胖具有持续性、复发性，需要综合治理，而GLP-1药物已在多个大规 模临床研究中证明在体重管理、血糖控制与代谢健康改善方面具有显著作用。 此次指南对利拉鲁肽、司美格鲁肽和替尔泊肽三类药物作出评估，认为其在体重下降和心代谢获益方面效果明确，同时也指出用药成 本、长期安全性和可及性仍是影响全球采用的重要因素。因此，WHO给出的推荐为"有条件纳入"，并呼吁各国在采纳时兼顾公平性与 卫生体系承载能力。 ▍长期管理思路被进一步强化 指南首先明确，肥胖是一种需要终身管理的慢性疾病，其治疗应覆盖从筛查、早期诊断到并发症管理的全链路过程。在必要时，可结 ...

Core Insights - The article discusses the significant impact of GLP-1 receptor agonists (GLP-1RAs) on obesity management, highlighting the challenge of weight rebound after discontinuation of medication [2] - A Danish randomized controlled trial indicates that incorporating supervised exercise during the treatment and withdrawal phases can significantly improve weight and body composition maintenance after one year [2] Research Design and Methodology - The trial included obese adults aged 18-65 with a BMI of 32-43 kg/m², progressing through three phases: - Induction phase (8 weeks): Strict low-calorie diet (~800 kcal/day), average weight loss of approximately 13.1 kg - Randomized maintenance phase (52 weeks): Participants were assigned to supervised exercise, liraglutide 3.0 mg/day, a combination of both, or a placebo - Follow-up phase (52-104 weeks): All interventions ceased at week 52, with assessments at week 104 for weight and body fat changes - The primary endpoint was weight change from randomization (week 0) to one year post-discontinuation (week 104), with secondary endpoints including percentage change in body fat [3] Key Findings and Evidence - The combination of supervised exercise and liraglutide showed a persistent advantage: one year post-discontinuation, the combination group had a lower weight (approximately -5.1 kg, statistically significant) and a significant decrease in body fat percentage (approximately -2.3 percentage points) compared to liraglutide alone [5] - Weight regain was more pronounced in the liraglutide-only group (approximately +6.0 kg) compared to the supervised exercise group (approximately +3.6 kg), indicating better stability in the exercise group [5] Body Composition and Functional Benefits - The combination group exhibited clearer reductions in body fat and waist circumference, with lean body mass increasing across all groups - Quality of life metrics indicated that the combination group outperformed the liraglutide-only group in energy/fatigue and physical function, while the supervised exercise group also showed improvements in energy/fatigue and pain [7] Mechanisms and Practical Implications - During the weight loss induction phase, the medication suppresses appetite and reduces intake, but after discontinuation, energy intake and appetite signals may revert to previous levels, leading to weight regain - Supervised exercise can enhance insulin sensitivity, increase resting energy expenditure, preserve lean body mass, and improve appetite regulation and psychological state, helping to establish a new energy balance during the withdrawal phase - Previous observations indicated that approximately 67% of weight loss achieved with semaglutide is regained after discontinuation, supporting the complementary relationship between medication and exercise [10] Conclusion - Obesity is a chronic and relapsing condition; while medications can effectively reduce weight, the long-term outcome depends on the ability to maintain exercise and lifestyle changes post-medication - Viewing supervised exercise as a long-term prescription, alongside medication and intensified during the withdrawal phase, is currently one of the most evidence-supported and feasible strategies [10]

Core Viewpoint - Eli Lilly Canada has launched ZEPBOUND™ KwikPen® (tirzepatide injection) in Canada, providing a new chronic weight management solution for adults with obesity or overweight [2][5]. Group 1: Product Overview - ZEPBOUND™ is a once-weekly injection approved for long-term weight control in conjunction with a healthy diet and regular exercise [2]. - It is suitable for adults with a Body Mass Index (BMI) of 30 or higher, or those with a BMI between 27 and 30 who have weight-related conditions such as hypertension, dyslipidemia, type 2 diabetes, sleep apnea, or cardiovascular diseases [2]. Group 2: Mechanism of Action - ZEPBOUND™ regulates appetite and metabolism by simultaneously activating two hormone receptors: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) [3]. - It is the first and only dual receptor agonist approved in Canada for long-term weight management, offering both weight loss and weight maintenance effects [3]. Group 3: Clinical Evidence - The approval of ZEPBOUND™ is based on results from four global SURMOUNT phase 3 clinical trials (SURMOUNT-1 to SURMOUNT-4) [5]. - In the SURMOUNT-1 study, 2,539 adults without diabetes but with obesity or overweight and related conditions participated. After 72 weeks, participants using the maximum dose (15 mg) lost an average of 21.8 kg (48 lbs), while those using the minimum dose (5 mg) lost an average of 15.4 kg (34 lbs). The placebo group lost an average of only 3.2 kg (7 lbs) [5]. Group 4: Health Challenges and Economic Impact - Obesity is a serious chronic disease affecting one in three Canadians, linked to over 200 diseases, including heart disease and type 2 diabetes [6]. - The annual economic loss related to obesity in Canada has reached CAD 27.6 billion, which is 20% higher than previous estimates [6]. Group 5: Reception and Advocacy - Medical professionals and patient organizations have welcomed the launch of ZEPBOUND™, highlighting it as an important advancement in obesity treatment [8]. - Experts emphasize the need for equitable access to treatment and recognition of the challenges faced by individuals with obesity, advocating for societal change and support [8].

Core Viewpoint - China has the highest number of overweight and obese individuals globally, with over half of the adult population affected, leading to significant health and economic implications [2] Group 1: Obesity Statistics - As of 2021, 16.4% of adults in China are classified as obese, and 34.3% as overweight, totaling approximately 532 million individuals, with nearly 100 million being obese [2] - By 2030, projections indicate that the number of overweight adults in China will reach 540 million, and the obese population will increase to 150 million, representing growth of 2.8 times and 7.5 times since 2000, respectively [2] - By 2035, it is estimated that one-quarter of the global population will be classified as obese, up from 14% in 2020 [2] Group 2: GLP-1 Drug Usage and Compliance - The introduction of GLP-1 drugs like semaglutide has transformed the weight loss market, although many users discontinue the medication after a period [3][5] - A study published in the journal "Obesity" found that 44% of patients remained on weight loss medication after three months, 33% after six months, and only 19% after one year [5] - For semaglutide users, the retention rates were higher, with 63% after three months, 56% after six months, and 40% after one year [5] Group 3: Effects of Discontinuation - A clinical trial indicated that participants who used semaglutide for 20 weeks lost an average of 10.6% of their body weight, but those who switched to a placebo regained an average of 6.9% of their weight [6] - Participants who continued semaglutide and lifestyle interventions maintained an average weight loss of 17.3% over 68 weeks, while those who stopped regained about two-thirds of their lost weight within a year [6] Group 4: Reasons for Discontinuation - Common side effects of GLP-1RA drugs include nausea, diarrhea, vomiting, constipation, abdominal pain, and gastroesophageal reflux, which may lead to discontinuation [8] - Approximately 17% of patients reported nausea even at low doses of semaglutide, with diarrhea and vomiting rates at 12.2% and 6.4%, respectively [8] - Drug supply issues have also been a concern since 2022, leading to shortages of semaglutide [9] Group 5: Recommendations for Discontinuation - It is advised to gradually reduce the dosage of GLP-1 drugs rather than stopping abruptly to mitigate increased hunger sensations [12][14] - Patients should monitor their appetite and weight closely after discontinuation, and if weight begins to increase, they may consider resuming medication at a lower dose [14] - Maintaining healthy eating habits and regular exercise is crucial to prevent weight regain after stopping medication [14][15] Group 6: Importance of Continued Medication - Long-term management of obesity is essential, as it is considered a chronic disease, similar to hypertension or heart disease [19] - In the STEP 5 trial, participants using semaglutide for two years lost an average of 15.2% of their body weight, with 77.1% of patients achieving at least a 5% weight loss [19] - The SELECT trial showed that patients who continued semaglutide for four years maintained an average weight loss of about 10% without rebound [19]