整理 | GLP1减重宝典内容团队 最近对 STEP 计划的五项随机对照试验进行的分析发现， 使用司美格鲁肽治疗肥胖的成年人比使用安慰剂的成年人更有可能减少或停 止使用抗高血压和降脂药物 。值得注意的是，两组之间的药物调整存在显著差异，司美格鲁肽使用者的减少幅度更大。 该研究结果于 2025 年 1 月 5 日在线发表在《肥胖》上，研究人员指出，司美格鲁肽是一种胰高血糖素样肽-1 (GLP-1) 受体激动剂，广 泛用于体重管理，并与多种代谢参数的改善有关。观察到的抗高血压和降脂药物使用量的减少与体重显着减轻对血压和血脂状况的已知 影响相一致。他们建议，通过促进治疗强度降低或停药，司美格鲁肽可能为患有肥胖相关心脏代谢疾病的个体简化用药方案提供额外的 优势。 基于上述背景，Beverly G. Tchang 及其同事旨在评估接受司美格鲁肽 2.4 毫克治疗的参与者与接受安慰剂治疗的参与者相比，抗高血 压和降脂治疗的变化。他们分析了五项司美格鲁肽对肥胖人群的治疗效果 (STEP) 试验的汇总数据。 为此，研究人员评估了司美格鲁肽 2.4 毫克在 STEP 临床试验中的疗效和安全性。在这项事后分析中，STEP 1、3 ...

以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 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。 内分泌早知道 solution for injection in pre-filled per semaglutide subcutaneous use 美国心脏病学会最新发布的指南 首次明确将司美格鲁肽和替尔泊肽 列为肥胖症治疗的优选药物 UNDERSTANDING OBESITY 添加小助手 商务合作/投稿/学术交流 备注「姓名+公司+职务+诉求」 美国心脏病学会（ACC）最新发布的《心血管健康体重管理专家共识》引发广泛关注。这份权威指南首次明确将司美格鲁肽和替尔泊 肽列为肥胖症治疗的优选药物,这两种新型营养刺激激素（NuSH）疗法正在重塑减肥治疗新格局。 ▍ 突破性疗法带来双重获益 研究证实，这类创新药物不仅能显著减轻体重，更能为心血管高风险人群提供额外保护。对于合并2型糖尿病或已有心血管疾病的患 者，NuSH疗法可有效降低心血管死亡、心梗及中风风险。其中，司美格鲁肽作为GLP- 1受体激动剂的代表，与双靶点激动剂替尔泊肽 共同构成了当 ...

Group 1 - Eli Lilly has halted an experimental drug study aimed at preventing muscle loss in obese patients due to strategic business considerations [1] - The trial was terminated on June 10, less than a month after its initiation, while a similar study for non-diabetic obese patients remains active [1] - The experimental injection was central to Eli Lilly's strategy for addressing muscle loss in patients undergoing rapid weight loss [1] Group 2 - The terminated trial was intended to follow 180 patients with type 2 diabetes who are obese or overweight for approximately 13 months, focusing on weight loss and fat reduction [1] - Eli Lilly had previously committed around $2 billion to acquire Versanis Bio to obtain bimagrumab, which was to be used in conjunction with its blockbuster drug Zepbound [1] - In a June study, Eli Lilly indicated that bimagrumab could help patients maintain muscle mass while using Novo Nordisk's weight loss drug Wegovy [2] Group 3 - Bimagrumab works by blocking a receptor that typically regulates muscle growth, and it was previously tested by Novartis in a small study involving diabetic patients [2] - In Novartis' early research, one out of 37 patients treated with bimagrumab developed pancreatitis and was hospitalized, raising concerns about the risk of pancreatitis in diabetic patients [2]

Core Viewpoint - The article discusses the significant weight loss effects of oral semaglutide in overweight or obese patients without diabetes, highlighting the results of the OASIS 1 study and the PIONEER PLUS study, which demonstrate its efficacy and safety in weight management and blood sugar control [6][20]. Group 1: OASIS 1 Study Findings - The OASIS 1 study showed that daily oral administration of 50mg semaglutide led to an average weight loss of 15.1% after 68 weeks, with 85% of participants achieving clinically meaningful weight loss (≥5%) [6][9]. - The study included 667 adults with a BMI of ≥30kg/m² or ≥27kg/m² with weight-related complications, randomly assigned to either the semaglutide group or a placebo group [6][8]. - The treatment demonstrated a significant difference in weight loss compared to the placebo group, which only saw a 2.4% reduction (p<0.0001) [9][11]. Group 2: PIONEER PLUS Study Insights - The PIONEER PLUS study focused on the effects of high-dose oral semaglutide on blood sugar control in patients with type 2 diabetes and obesity, showing that higher doses (25mg or 50mg) resulted in better glycemic control and weight loss compared to the standard 14mg dose [20]. - Results indicated that the 50mg dose group achieved an average HbA1c reduction of 2.0%, with 63% of patients reaching the target HbA1c <7.0% [18][20]. - The study also reported that patients in the higher dose groups had a higher percentage of weight loss exceeding 5% or 10% compared to the standard dose group [18][20]. Group 3: Safety and Tolerability - The overall tolerability of semaglutide treatment was good, with 80% of patients reporting gastrointestinal adverse effects, mostly mild to moderate [13][15]. - The incidence of any adverse events was higher in the semaglutide group (91.9%) compared to the placebo group (85.6%), but serious adverse events were relatively low [15]. - Common adverse events included nausea (51.8% in the semaglutide group) and gastrointestinal disorders, but no fatal events were reported [15].

以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 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。 最新研究显示，当实验小鼠的饮食中去除半胱氨酸后，短短7天内体重骤降30%，这一突破性发现为代谢调控研究开辟了新方向。 在全球肥胖问题日益严峻的背景下，这项研究无疑为理解体重调控机制提供了全新视角。 当前全球肥胖人口已突破总人口的六分之一，传统减肥方式如低碳饮食、生酮疗法等虽然各具特色，但效果参差不齐。这项发表在权威 期刊的研究首次揭示，半胱氨酸在能量代谢中扮演着关键角色。实验过程中，研究人员观察到停止供应该氨基酸的小鼠不仅体重急剧下 降，更令人惊讶的是，在恢复正常饮食后，其体重能够快速回升。这种可逆的体重变化模式暗示着人体内可能存在着类似代谢"开关"， 为未来开发新型减肥干预措施提供了重要线索。 深入分析表明，半胱氨酸缺乏可能触发了某种未知的代谢重编程机制。科学家推测，这种氨基酸或是连接能量摄入与消耗的重要媒介， 其缺失直接导致体内能量平衡系统发生剧烈调整。值得注意的是，这种减重效果远超现有饮食干预手段，其背后隐藏的分子机制或将改 写我们对体 ...

Core Viewpoint - Tirzepatide has gained unprecedented attention as an effective solution for sustainable weight loss, initially developed for treating type 2 diabetes, and has proven effective in controlling blood sugar and aiding weight loss [4] Group 1: Clinical Trial Data - Mounjaro has shown significant results in the SURMOUNT-5 phase 3 clinical trial, where participants lost an average of 50.3 pounds (22.8 kg) over 72 weeks [6] - Experts highlight that Mounjaro is one of the first drugs to effectively combine weight loss and metabolic health improvement, marking a cornerstone in modern obesity treatment [6] Group 2: Mechanism of Action - Mounjaro employs a dual-target mechanism, affecting two key hormones, GIP and GLP-1, which helps patients feel full longer and reduces binge eating impulses [6][7] - This multi-target approach is noted to provide comprehensive support for weight management, leading to better long-term results compared to traditional methods [7] Group 3: Health Benefits Beyond Weight Loss - Tirzepatide has shown improvements in metabolic indicators such as blood pressure, blood lipids, BMI, and waist circumference, which are critical risk factors for cardiovascular diseases [8] - Ongoing SURPASS-CVOT trials aim to clarify the cardiovascular benefits of Tirzepatide compared to other treatments [8] Group 4: Broader Implications - The drug has been approved for treating moderate to severe obstructive sleep apnea (OSA) in obese adults, indicating a close link between obesity and OSA [9] - Positive results from the SUMMIT trial show a 38% reduction in heart failure risk among patients treated with Tirzepatide, along with significant improvements in heart failure symptoms and physical ability [9] - The SYNERGY-NASH study indicates that Tirzepatide can help 73% of patients achieve resolution of metabolic dysfunction-associated fatty liver disease (MAFLD) without worsening fibrosis [9] Group 5: Future Outlook - The impact of obesity extends beyond health, contributing to various complications and economic burdens on society [10] - Effective weight loss interventions can significantly reduce the risk of related conditions, such as type 2 diabetes and sleep apnea, by over 50% for patients without complications [12] - Experts believe that advancements in science may lead to a turning point in the battle against obesity, making weight loss less of a struggle [12]

Core Insights - Novo Nordisk is set to present 35 abstracts related to its diabetes and obesity portfolio at the EASD congress 2025, highlighting the health benefits and weight loss effects of semaglutide, along with new obesity pipeline therapies [1][3][4] Company Developments - The company will host an R&D investor event on 17 September to discuss the science and abstracts presented at the congress, which will be available via live webcast [2] - Semaglutide is recognized for having the broadest approved indications for obesity and type 2 diabetes, contributing to weight loss and cardiovascular protection [3] Research Presentations - Key presentations include the SOUL trial on oral semaglutide's cardiovascular outcomes, and various studies on the effectiveness of semaglutide and its impact on eating behaviors and body composition [5][7][8] - The REDEFINE trials will present data on the efficacy of cagrilintide and amycretin as next-generation obesity treatments [11][17] Product Information - Semaglutide is marketed under the brand names Wegovy® (2.4 mg injection), Ozempic® (1.0 mg injection), and Rybelsus® (14 mg oral) [14] - The drug has a well-established safety profile supported by over 33 million patient-years of exposure since its launch in 2018 [13]

Financial Data and Key Metrics Changes - The company is focused on next-generation obesity therapies, particularly therapeutic peptides targeting hormone pathways, with a strong emphasis on scalability and combinability [2][3] - The clinical stage assets include MET-097i, an ultra-long-acting GLP-1 receptor agonist, which is expected to enter phase three trials later this year [3][4] - The company reported a 10% to 11% placebo-adjusted weight loss at 12 weeks for MET-097i, which is competitive within the landscape [15][30] Business Line Data and Key Metrics Changes - MET-097i has shown a unique profile with a half-life of 18 days, allowing for better tolerability and efficacy compared to existing treatments [11][12] - The amylin analog MET-233i demonstrated up to 8.5% placebo-adjusted weight loss with well-tolerated starting doses [5][45] - The oral peptide strategy aims to deliver injectable-like efficacy at lower doses, with clinical data expected later this year [6][65] Market Data and Key Metrics Changes - The company is positioning itself as a best-in-class candidate in the obesity treatment market, targeting a significant portion of the population that benefits from dual agonists [40][56] - The competitive landscape includes drugs like tirzepatide, with MET-097i aiming to match or exceed its efficacy and tolerability [30][40] Company Strategy and Development Direction - The company is focused on developing scalable oral peptides that can provide the same benefits as injectables, addressing the limitations of small molecules [66][67] - The strategy includes exploring combination therapies with MET-097i and MET-233i, leveraging their compatible pharmacokinetics for enhanced efficacy [46][57] - The long-term vision includes maintenance therapies that could potentially reduce the frequency of dosing, aiming for quarterly dosing strategies [75][76] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming clinical data and the potential for MET-097i to set a new standard in obesity treatment [9][19] - The company anticipates significant advancements in the obesity treatment landscape, with a focus on maintaining weight loss over extended periods [74][76] - Management highlighted the importance of tolerability and efficacy in their drug development, aiming to provide alternatives for patients who struggle with existing therapies [56][58] Other Important Information - The company is preparing for multiple data readouts in the coming months, including interim data from ongoing studies [19][42] - The development of prodrugs and combination therapies is seen as a key area for future growth and innovation [75][76] Q&A Session Summary Question: Can you elaborate on the long half-life of MET-097i and its impact on tolerability? - The long half-life allows for a smoother concentration rise, reducing gastrointestinal adverse events associated with rapid concentration changes [11][12] Question: What are the expectations for the upcoming VESPER-1 and VESPER-3 studies? - The target profile for MET-097i is to achieve dual agonist-like efficacy, with expectations of over 10% placebo-adjusted weight loss at 28 weeks [30][32] Question: How does the company differentiate itself from competitors in the obesity treatment market? - The company aims to provide a more consumer-friendly profile with fewer titration steps and a focus on monthly dosing, setting it apart from other treatments [40][56]

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。 今年两会热词榜上，"减肥"意外走红。 国家卫健委发出紧急提醒：体重管理刻不容缓，全民健康亮红灯！这绝非推崇"以瘦为美"或制造焦虑，而是基于严峻健康现实。肥胖已成全 球公共卫生危机，是多种代谢疾病的元凶，直接引发2型糖尿病、心血管疾病及众多难言之隐。身边案例不胜枚举：奇点糕的朋友三番五次 医院求诊，查打嗝做完肠胃镜毫无异常，医生建议：减肥；足跟剧痛就诊，医生直言：体重过大压迫所致，减肥是根本。是的，明天就开 始！ 体重管理双管齐下：一方面靠自律，合理运动、规律作息、科学饮食（详见往期文章）；另一方面借助外力，包括药物干预或手术治疗。 目前市场上司美格鲁肽、利拉鲁肽等GLP-1受体激动剂已获减重适应症批准。这类药物本质是模拟人体内天然生物活性肽GLP-1，参与能量 平衡调节、食欲控制与体重管理。 近期重磅消息！美国斯坦福大学Katrin J. Svensson团 ...

Viking Therapeutics (VKTX) Conference Call Summary Company Overview - **Company**: Viking Therapeutics (VKTX) - **Date**: August 19, 2025 - **Key Speakers**: Brian Lyon (President and CEO), Maryann Mancini (COO), Karen Modesto (Executive Director, Clinical Development), Greg Zanti (CFO) Core Industry and Product Focus - **Industry**: Biotechnology, specifically focused on obesity treatment - **Product**: VK2735, a dual agonist of GLP-1 and GIP receptors Key Points and Arguments Phase II Study Results - Viking announced top-line results from the Phase II Venture oral dosing trial for VK2735, aimed at treating obesity [3][5] - The study achieved its primary and secondary endpoints, demonstrating statistically significant reductions in body weight [11] - Subjects receiving VK2735 showed weight loss up to **12.2%** from baseline and **10.9%** relative to placebo [12] - The treatment was reported as safe and well-tolerated, with most adverse events classified as mild or moderate [11][16] Weight Loss and Efficacy - VK2735 demonstrated a progressive weight loss trend throughout the 13-week treatment period, with no evidence of plateauing [12] - Up to **97%** of subjects achieved at least **5%** weight loss compared to **10%** for placebo, and **80%** achieved at least **10%** weight loss compared to **5%** for placebo [13] - The study included an exploratory arm assessing the transition from high daily doses to lower maintenance doses, showing effective weight retention [14] Safety and Tolerability - Adverse event rates were higher in VK2735 treated cohorts compared to placebo, primarily due to gastrointestinal (GI) events [16][17] - **11%** of VK2735 treated subjects discontinued the study early, compared to **5%** for placebo [16] - GI-related adverse events were most prevalent in the first week, with rates declining over time [18] Future Development Plans - Viking plans to initiate a Phase III registration program for VK2735, named the Vanquish studies, which will evaluate the drug in adults with obesity and those with type 2 diabetes [6][7] - The company is also developing an oral tablet formulation of VK2735, which could provide an alternative treatment option for patients [7][8] Market Positioning and Strategy - The company believes that the dual formulation (oral and subcutaneous) could mitigate safety challenges when transitioning patients between treatments [8] - Viking aims to explore the potential for lower maintenance doses based on the encouraging results from the maintenance dosing cohort [19] Questions and Answers Insights - Discussions highlighted the need for a slower titration rate in future studies to improve tolerability [22][56] - The company is considering the implications of dosing regimens, including the potential for less frequent dosing to enhance patient compliance [120] Other Important Considerations - The results from the exploratory maintenance dosing cohort provide a proof of concept for transitioning patients to low-dose maintenance therapy [19] - Viking's approach to addressing GI tolerability through optimized titration regimens is a key focus for upcoming studies [34][56] This summary encapsulates the critical insights from the Viking Therapeutics conference call, focusing on the company's advancements in obesity treatment through VK2735 and its strategic plans moving forward.