整理 | GLP1减重宝典内容团队 替尔泊肽（Tirzepatide）和司美格鲁肽（Semaglutide）都是GLP-1类2型糖尿病药物，也可以帮助人们减肥。 ▍ 最近的一项研究结果表明，替尔泊肽在帮助肥胖或超重患者减肥方面可能比司美格鲁肽更有效 发表在 JAMA Internal Medicine 上的一项名为《Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity》的研究比较了司美格鲁肽 和替尔泊肽对肥胖或超重成年人的有效性。 研究人员总共将 18,386 名参与者纳入了倾向评分匹配队列。其中，52% 的人患有 2 型糖尿病，参与者的平均年龄为 52 岁。参与者的平均随访时间为 165 天，略高于 50% 的参与者停止了每种药物的治疗。研究人员记录了参与者中发生的胃肠道不良事件，发现两种药物组的风险相似。 研究人员通过电子健康记录收集信息并链接第三方数据。他们观察了参与者在三个月、六个月和一年时体重的变化。 结果显示，替尔泊肽组在减重比例方面展现出显著优势：体重减轻≥5%的受试者比例： 替尔泊肽组为约 ...

Core Viewpoint - Novo Nordisk's Kyinsu® (IcoSema) has received EU approval, combining weekly insulin with GLP-1 receptor agonist for better management of type 2 diabetes in adults [4][6]. Group 1: Product Overview - Kyinsu® integrates Icodec insulin for sustained blood sugar control and Semaglutide for weight management [7]. - The product allows for a single weekly injection, simplifying treatment with a maximum dosage of 350 units of Icodec and 1.0 mg of Semaglutide [7]. - Clinical trials involving over 2,500 adult type 2 diabetes patients demonstrate Kyinsu®'s efficacy in reducing HbA1c levels and achieving significant weight loss with lower hypoglycemia rates compared to daily insulin regimens [7]. Group 2: Industry Impact - The weekly injection format of IcoSema addresses the common delay in insulin therapy initiation among type 2 diabetes patients, where about 50% delay treatment for over two years, increasing complication risks [6]. - The design of Kyinsu® aims to enhance patient adherence to treatment and offers a new option for personalized therapy [6].

Core Viewpoint - Novo Nordisk is undergoing a significant leadership transition driven by its largest shareholder, the Novo Foundation, aiming for more aggressive measures to revitalize the company amid recent challenges in the obesity and diabetes drug market [2][5]. Group 1: Leadership Changes - The board chairman Helge Lund and six other board members will resign, with former CEO Lars Rebien Sørensen returning to the CEO position for a term of two to three years [2][5]. - Sørensen emphasized the need for a new perspective and energy to support management in crucial transformation processes [4][5]. - The new board will support CEO Maziar Mike Doustdar, who has been pushing for a major restructuring that has led to thousands of job cuts and the closure of several research departments [4][5]. Group 2: Market Challenges - Novo Nordisk's stock has dropped 36% year-to-date, with a further decline of 1.4% following the announcement of board changes [4]. - Analysts have noted that the company has fallen behind competitors like Eli Lilly due to a slow response to changes in the U.S. market [5][6]. - Sørensen acknowledged that the board failed to recognize the importance of market changes in a timely manner, impacting the company's ability to adjust its strategy [8]. Group 3: Strategic Focus - The Novo Foundation expressed dissatisfaction with the previous board's speed and effectiveness in addressing the rapidly changing obesity and metabolic market [5][6]. - The new board will focus on members with consumer experience, as GLP-1 drugs are becoming more consumer-oriented [5][6]. - The leadership changes reflect a desire for Novo Nordisk to adopt a more proactive approach in the competitive obesity and diabetes treatment market [8].

Core Viewpoint - Tirzepatide is more effective than Semaglutide for weight loss in adults with overweight or obesity, as evidenced by a study published in JAMA Internal Medicine [4][5][15] Group 1: Study Overview - The study included 18,386 participants, with 52% having type 2 diabetes and an average age of 52 years [6] - The average follow-up time was 165 days, with over 50% of participants discontinuing treatment [6] - Researchers recorded gastrointestinal adverse events, finding similar risks between both drug groups [6] Group 2: Weight Loss Results - The results showed significant advantages for the Tirzepatide group in weight loss percentages: - ≥5% weight loss: Tirzepatide ~81.8%, Semaglutide 66.5%, risk ratio 1.76 [10] - ≥10% weight loss: Tirzepatide ~62.1%, Semaglutide 37.1%, risk ratio 2.54 [10] - ≥15% weight loss: Tirzepatide ~42.3%, Semaglutide 18.1%, risk ratio 3.24 [10] - Weight changes at follow-ups were also significantly greater for Tirzepatide: - 3 months: Tirzepatide 5.9%, Semaglutide 3.6% - 6 months: Tirzepatide 10.1%, Semaglutide 5.8% - 12 months: Tirzepatide 15.3% [12] Group 3: Expert Insights - Dr. Patricia Rodriguez highlighted that patients using Tirzepatide were more than twice as likely to lose 10% of their weight compared to those using Semaglutide, and three times more likely to lose 15% [16] - Dr. Nick Stucky noted that while Tirzepatide's effectiveness is superior, both medications resulted in significant weight loss, with no difference in gastrointestinal adverse event risks [16] - Factors such as drug availability and insurance coverage may influence the choice between these medications [16]

Core Insights - The article discusses the alarming rise in global cancer cases, projected to exceed 35 million by 2050, a 77% increase from 2022, driven by factors such as smoking, alcohol consumption, obesity, and air pollution [1] - A novel cancer treatment mechanism developed by Professor Liang Run-song's team at Hong Kong Polytechnic University focuses on starving cancer cells by targeting their specific amino acid needs, particularly arginine [3][10] - The drug BCT-100, which utilizes this mechanism, has been approved for clinical trials by the FDA and targets arginine-dependent cancers like acute myeloid leukemia and melanoma [4][3] Research and Development - Liang Run-song's background in chemistry and molecular biology has shaped his focus on converting protein molecules into therapeutic agents for difficult-to-treat diseases [2] - The research team discovered that rapidly proliferating cancer cells have a heightened demand for specific nutrients, particularly certain amino acids, leading to the hypothesis that reducing these nutrients could inhibit cancer cell growth [10][3] - The development of BCT-100 involves injecting arginase to lower blood arginine levels, effectively starving cancer cells while sparing normal cells [3][11] Clinical Trials and Future Prospects - BCT-100 is currently in the third phase of clinical trials, with hopes for market availability in the near future [4][13] - The research team has also expanded their focus to metabolic diseases, developing a long-acting formulation of arginase, ABarginase, which shows promise in treating obesity and diabetes [5][15] - ABarginase has received recognition for its innovative design and is currently advancing through preclinical trials with support from Roche's accelerator program [6][5] Industry Context - The biotechnology startup ecosystem in Hong Kong is thriving, with a significant increase in the number of startups and a growing number of unicorns in high-growth sectors like biotechnology [7] - Liang Run-song emphasizes the importance of local support in terms of funding and facilities for the successful translation of research into clinical applications [8][19] - The establishment of the He Tao Innovation and Technology Park is seen as a potential hub for biotechnology development, providing essential resources for startups [19]

Core Viewpoint - The article discusses the development of a new oral medication, ATR-258, which shows similar blood sugar regulation and weight loss effects as injectable GLP-1 receptor agonists, without the common side effects associated with GLP-1 drugs [2][3][15]. Group 1: Drug Development and Mechanism - ATR-258 is a β2 adrenergic receptor agonist that activates skeletal muscle metabolism positively, improving metabolic health without reducing muscle mass [3][6]. - The research utilized ligand-based virtual screening and chemical evolution techniques to develop a selective agonist that couples with G protein-coupled receptor kinases (GRK) [8][12]. - ATR-258 demonstrates lower cardiac side effects compared to standard β2 receptor agonists and lower muscle side effects compared to GLP-1 receptor agonists like liraglutide [12][15]. Group 2: Clinical Trials and Future Prospects - A Phase 1 clinical trial involving 48 healthy subjects and 25 type 2 diabetes patients showed that ATR-258 has good pharmacokinetic properties and tolerability [13]. - Atrogi AB plans to conduct a larger Phase 2 clinical trial to observe the positive effects seen in preclinical animal models in human patients with type 2 diabetes or obesity [16].

Core Viewpoint - The development and application of GLP-1 receptor agonists, particularly Semaglutide, have significantly transformed obesity treatment, demonstrating effective weight loss and potential heart protection properties [2][5]. Group 1: Mechanism of Action - Semaglutide primarily reduces weight by suppressing appetite, leading to decreased caloric intake, although its direct effects on peripheral metabolism remain unclear [2]. - Recent research indicates that Semaglutide's effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex (DVC), which play a crucial role in appetite regulation and metabolism [3][5]. - Activation of Adcyap1+ neurons promotes fat loss without significant muscle loss and minimizes side effects like nausea, paving the way for safer and more effective weight loss medications [6][8]. Group 2: Research Findings - The study published in Cell Metabolism reveals that Semaglutide activates specific neurons in the DVC, leading to reduced food intake and weight loss while enhancing fat utilization [3][5]. - The research team found that eliminating Adcyap1+ neurons in the AP/NTS significantly reversed Semaglutide's appetite-suppressing effects and fat reduction, indicating their critical role in the drug's mechanism [6][8]. - The findings provide a theoretical foundation for developing more precise anti-obesity therapies that target the Adcyap1+ neuronal pathway, emphasizing a "fat loss while preserving muscle" approach [8].