整理 | GLP1减重宝典内容团队 当地时间18日，诺和诺德与礼来几乎在同一时间节点抛出重磅进展。一方正式向监管机构递交上市申请，试图通过"机制叠加"进一步抬 升减重治疗的效果上限；另一方则公布关键Ⅲ期研究结果，瞄准"口服替代注射"的长期管理场景，并同步推进上市审批程序。这一高度 同步的动作，标志着围绕下一代减重新药的竞争，已不再局限于实验室和论文，而是正式进入商业化冲刺阶段。 过去数年，GLP-1类药物从糖尿病治疗"意外"延伸至减重领域，迅速演变为全球医药产业最炙手可热的赛道之一。但随着注射型产品逐 步铺开、渗透率持续提升，单一机制、单一给药方式的天花板开始显现。无论是从疗效增量、患者依从性，还是从支付方可承受成本来 看，新一轮竞争都必须给出更明确的答案。 从"更强疗效"到"更易长期使用" 诺和诺德的最新动作，核心在于"机制叠加"。在现有GLP-1路径基础上，通过引入多靶点协同，试图进一步放大体重下降幅度，并改善 代谢相关指标。这一策略并非单纯追求短期减重数字，而是希望在肥胖相关并发症管理上建立更强的临床说服力。 相比之下，礼来的侧重点明显不同。其公布的Ⅲ期研究结果，将焦点放在口服方案的可行性上。口服替代注 ...

Core Viewpoint - The article discusses the emerging role of GLP-1 receptor agonists in managing heart failure with preserved ejection fraction (HFpEF), highlighting their potential cardiovascular benefits beyond weight loss [6][7]. Group 1: HFpEF and GLP-1 Research - HFpEF is becoming the most common type of heart failure globally, closely linked to rising obesity rates and the prevalence of type 2 diabetes [6]. - A recent study utilizing the Medicare claims database found that patients with obesity-related HFpEF and type 2 diabetes who started treatment with semaglutide or tirzepatide had over a 40% reduction in the risk of hospitalization for heart failure or all-cause mortality compared to those using sitagliptin [6][7]. - The study included over 58,000 patients, showcasing the significance of real-world evidence in complementing traditional clinical trials [7]. Group 2: Implications of GLP-1 Treatment - Despite previous beliefs that tirzepatide was superior for weight loss, it did not show a significant advantage in reducing heart failure hospitalization or mortality risk in this study, suggesting that the benefits of GLP-1 drugs in HFpEF may not solely depend on weight loss [7]. - The findings indicate that GLP-1 therapies are reshaping medical practice and public health, with potential implications for millions of HFpEF patients [7]. - The study reinforces the clinical value of GLP-1 treatments in managing cardiometabolic diseases, extending beyond previously established benefits [7].

Core Viewpoint - The article emphasizes the importance of body composition analysis over mere weight or BMI for determining the suitability of GLP-1 medications for weight management [4][10]. Group 1: Suitability of GLP-1 Medications - The use of GLP-1 medications should not be based solely on weight or BMI but should include body composition analysis as a critical decision-making factor [4][6]. - Rocio Salas-Whalen, a specialist in obesity medicine, highlights that weight loss can result from muscle loss, water reduction, or minimal fat changes, which do not necessarily indicate improved metabolic health [6][10]. - Body composition metrics, such as skeletal muscle content, body fat percentage, and visceral fat levels, are essential for assessing health risks [6][8]. Group 2: Health Indicators - Visceral fat is identified as a particularly dangerous indicator, associated with inflammation and metabolic diseases, while body fat percentage reflects overall fat burden [8][10]. - Salas-Whalen recommends that women maintain a body fat percentage below 28% and men below 20% for optimal health [8]. - Skeletal muscle is crucial for metabolic health, as it plays a significant role in glucose utilization and reducing insulin resistance [8][10]. Group 3: Treatment Goals and Recommendations - The goal of weight loss treatment should focus on body recomposition, aiming to reduce fat while preserving or increasing muscle mass [8][10]. - GLP-1 medications should not be prescribed indiscriminately and should be based on clear medical indications [10]. - The World Health Organization suggests GLP-1 medications for adults with a BMI of 30 or higher, but this does not imply universal applicability for all individuals [10].

Core Insights - Kailera has officially launched three global multi-center Phase III clinical trials for its core candidate drug KAI-9531, targeting obesity with type 2 diabetes and obesity without diabetes, marking a critical stage in clinical validation [4] - The trials aim to enroll over 4,700 participants, demonstrating the company's commitment to long-term safety and efficacy validation of the drug [4] - The studies are designed to progress simultaneously across multiple countries and regions, with completion expected between March and April 2028, potentially leading to regulatory submission and commercialization [6] Clinical Development - The Phase III trial for obesity with diabetes plans to enroll approximately 1,700 participants, while the two trials for obesity alone aim for around 1,200 and 1,800 participants respectively [4] - Kailera is accelerating the late-stage development of its obesity and metabolic disease product pipeline to secure a position in the competitive GLP-1 and novel metabolic drug market [6] Industry Context - GLP-1 receptor agonists are a new class of hypoglycemic drugs that enhance insulin secretion and suppress glucagon secretion in a glucose-dependent manner, also delaying gastric emptying and reducing appetite, thus aiding in blood sugar control and weight loss [14]

Core Viewpoint - Novo Nordisk's GLP-1 drug Wegovy has received conditional marketing authorization from Health Canada for treating adults with moderate to severe liver fibrosis (F2-F3) associated with non-alcoholic steatohepatitis (NASH), marking its expansion into liver disease treatment beyond obesity and metabolic disorders [5]. Regulatory Perspective - The conditional approval indicates that further research is needed to validate long-term efficacy and safety, reflecting a cautious support from regulators for products with clear potential clinical benefits in the NASH field, which currently lacks established treatment options [7]. Market and Medical Value - As Wegovy's indications continue to expand, its positioning within the metabolic disease spectrum is evolving from a singular weight loss and diabetes treatment to a comprehensive therapeutic tool addressing obesity, metabolic syndrome, and related organ damage, thereby stretching its commercial and medical value boundaries in the global market [7].

Core Viewpoint - GLP-1 receptor agonists, such as semaglutide, not only alter external appearance but also significantly impact body composition, which is crucial for understanding overall health effects beyond standard weight loss metrics [4][5][6] Group 1: Impact on Body Composition - The study analyzed 241 patients using semaglutide, comparing abdominal CT scans before and after five years of treatment, revealing significant changes in body composition [8] - In the weight loss group, reductions were observed in visceral fat area, subcutaneous fat area, muscle area, and liver volume, with an increase in liver density, indicating positive changes for cardiovascular metabolic health [8] - Conversely, in the weight gain group, increases in visceral fat area, subcutaneous fat area, and intermuscular fat area were noted, along with a decrease in muscle density, highlighting the importance of body composition metrics [8][9] Group 2: Importance of Advanced Metrics - Traditional clinical assessments like weight, waist circumference, and BMI fail to capture critical tissue-specific changes that can be evaluated through CT scans, which are essential for understanding the full impact of GLP-1 agonist treatments [9]

Core Viewpoint - The article highlights the significant achievements of Innovent Biologics in the field of metabolic disease treatment, particularly through the dual receptor agonist, Ma Shidu Te (MGC/GLP-1), which has shown promising results in clinical trials for type 2 diabetes and weight management [10][12]. Group 1: Clinical Research Achievements - Innovent Biologics announced the publication of two Phase III clinical trial results for Ma Shidu Te in the prestigious journal Nature, marking the first time two such studies in the metabolic and endocrine disease field have been published back-to-back [10][11]. - The DREAMS-1 trial involved 320 participants with type 2 diabetes who did not achieve target results through diet and exercise, showing significant reductions in HbA1c levels with Ma Shidu Te compared to placebo [13][15]. - The DREAMS-2 trial included 731 participants whose blood sugar was poorly controlled on metformin, demonstrating that Ma Shidu Te significantly outperformed the comparator drug in reducing HbA1c levels [14][15]. Group 2: Efficacy and Safety - Ma Shidu Te achieved a 2.02% reduction in HbA1c levels at 24 weeks in the DREAMS-1 trial, with 81.8% of participants in the 6mg group reaching HbA1c levels below 7%, compared to only 11.7% in the placebo group [15]. - In the DREAMS-2 trial, the 6mg group achieved a 1.66% reduction in HbA1c, with 70.4% of participants reaching the same target, indicating strong efficacy in blood sugar control [15][16]. - The overall safety profile of Ma Shidu Te was consistent with previous studies, showing good tolerability and no new safety signals, with gastrointestinal side effects being the most common [19]. Group 3: Broader Implications - The successful results of Ma Shidu Te not only contribute to the treatment of obesity and diabetes but also reflect China's growing capabilities in drug development and innovation on the global stage [10][12]. - The dual receptor mechanism of Ma Shidu Te offers a unique advantage in managing weight and metabolic health, particularly for the Chinese population, which faces specific challenges related to visceral fat accumulation [18]. - The ongoing research and development efforts by Innovent Biologics aim to expand the indications for Ma Shidu Te, further enhancing its role in global diabetes and weight management strategies [12][19].

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。 《柳叶刀》（The Lancet）近日刊登了一项涵盖全球八大地区的研究，聚焦全身及腹部肥胖与高血压之间的关系。该研究深入分析了全球各地 不同人群内部及群体间BMI与腰高比的关联，并对这两个指标在高血压患者与非高血压患者之间的差异进行了量化。结果显示，BMI能够较为 准确地区分腹部脂肪含量高低的中青年人群，准确度达到中等偏高水平；同时，BMI和腰高比这两个指标均可有效区分高血压患者与非高血压 人群。 肥胖通常通过体重指数（BMI，即体重与身高的比值）以及腹部肥胖指数来评估。本文探讨了全球不同地区人群内部及地区之间的BMI与腰高比 （WHtR，即腰围与身高的比值）的关系，并进一步量化了这两个指标在高血压患者与非高血压人群之间的差异。 01 • 背景 02 • 方法 本研究收集了1990至2023年间，全球八大地区20-64岁一般人群中关于BMI、WHtR与高血压 ...

以下文章来源于内分泌早知道 ，作者关注内分泌的 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。 对于2型糖尿病患者来说，外周动脉疾病（PAD）是个不容忽视的"隐形杀手"。它不仅严重影响患者行动能力，更会显著降低生活质 量，甚至增加死亡风险。然而目前临床上能有效改善PAD症状的药物却寥寥无几。 作为GLP- 1受体激动剂的明星药物，司美格鲁肽最初以出色的降糖效果闻名。但随着研究深入，人们发现它更像一个"多面手"——不仅 能控制血糖、减轻体重，还对心血管、肾脏等多个系统都有显著保护作用。更令人振奋的是，早前STRIDE试验的初步数据就显示，每 周注射1.0mg司美格鲁肽，可以明显改善合并PAD的2型糖尿病患者的身体机能和生活质量。 内分泌早知道 . 最新发表在权威期刊《Di a be t e s Ca r e》上的研究给出了更确凿的证据。这项基于STRIDE试验的深入分析采用随机双盲、安慰剂对照 的严格设计，重点探讨了司美格鲁肽对PAD患者的功能改善作用是否在不同特征人群中具有普遍性。这一发现为临床治疗提供了重要参 考。 ▍ 研究目标 1.司美格鲁肽的疗效是 ...

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。 越来越多的研究都在揭示，缺觉简直是健康和身材的"头号敌人"。 别说白天精神萎靡，最可怕的是，体重直线上升的风险也随之大增。 流行病学数据显示，每晚睡眠少于6小时的人，比那些保证7到9小时睡眠的人，变胖的概率高出近50%！可以说，别人搭电梯慢悠悠地往上， 你却按下了火箭加速键。 如果能够多睡一会儿，是不是就能把超重的风险拉下来，轻松瘦几斤呢？事实证明，还真是这样！ 最新登上权威医学期刊《JAMA Internal Medicine》的研究，首次直接证实：多睡觉，真的能辅助减肥。 这项研究专门招募了80位超重成年人，年龄介于21到40岁，BMI在25.0到29.9之间，而且平时睡眠时间都不足6.5小时。 研究团队将他们随机分为两组：一组维持原有作息不变，另一组则接受个性化睡眠延长建议，目标是每天多睡1小时。 首先，所有参与者先经历两周的原始睡眠阶段，随后进入两周 ...