智通财经APP讯，信达生物(01801)发布公告，信尔美®(玛仕度肽注射液，胰高血糖素"GCG"/胰高血糖 素样肽-1"GLP-1"双受体激动剂)高剂量9mg用于成人中重度肥胖患者长期体重控制的上市申请已获中国 国家药品监督管理局(NMPA)药品审评中心(CDE)受理。玛仕度肽有望在减重手术之外，为中国中重度 肥胖人群提供一个强效、安全的新治疗选择。 • 此外，研究还观察到玛仕度肽9mg可显著降低部分受试者的肝脏脂肪含量，较基线平均百分比降幅达 71.9%，并在血压、血脂、血尿酸等关键心血管代谢指标及腰围上也展现出显著的全面改善。 • 玛仕度肽9mg的安全性良好，未发现新的安全性信号。 有关GLORY-2研究达成所有终点的详细数据，计划在未来的国际学术期刊或学术大会上公布。 信尔美®(玛仕度肽注射液)9mg是目前唯一采用2步剂量滴定即可实现治疗1年超过20%减重的GLP-1类药 物，其开发为中国中重度肥胖患者提供了减重手术之外的有效体重管理的循证医学证据。玛仕度肽高剂 量9mg上市申请获得受理，从针对广阔超重/肥胖人群的2-4-6mg，到如今针对中重度肥胖人群的3-6- 9mg，这一布局源于深刻的科学洞察与明 ...

Core Viewpoint - The article emphasizes the importance of adequate protein intake while using semaglutide, a GLP-1 receptor agonist, for weight loss and overall health maintenance [2][5]. Group 1: Importance of Protein Intake - Sufficient protein intake is crucial during semaglutide treatment to maintain muscle mass [2][4]. - A balanced diet including protein, vegetables, and whole grains is recommended to enhance fiber intake and reduce side effects like constipation [2][5]. Group 2: Mechanism of GLP-1 Drugs - GLP-1 receptor agonists promote insulin secretion by activating GLP-1 receptors on pancreatic beta cells, which is glucose-dependent [6]. - They inhibit glucagon secretion from pancreatic alpha cells, helping to lower blood sugar levels [6]. - GLP-1 drugs delay gastric emptying, controlling postprandial blood sugar spikes [7]. - They also regulate appetite by acting on the brain's appetite centers, aiding in food intake reduction and weight management [8]. Group 3: Metabolic Effects - Research indicates that GLP-1 drugs not only increase satiety but also directly influence metabolism [10]. - Individuals using GLP-1 analogs exhibit increased metabolic activity, leading to higher energy expenditure and potential weight loss [11][13].

Core Insights - The article discusses groundbreaking research published in Nature that reveals the complex biological mechanisms behind obesity and weight loss, challenging traditional views of fat as merely an energy storage tissue [6][7]. Group 1: Obesity Mechanisms - Fat tissue is described as a complex "micro-society" composed of various cell types that communicate to maintain metabolic balance, rather than just a storage depot for energy [7]. - The study identifies five catastrophic changes in fat tissue during obesity: 1. An "inflammatory storm" occurs with a significant increase in immune cells, particularly lipid-associated macrophages (LAMs), leading to chronic inflammation [8]. 2. The metabolic system of fat cells becomes overloaded and dysfunctional, resulting in the accumulation of toxic byproducts [9]. 3. Cells within fat tissue exhibit signs of aging, activating senescence-associated secretory phenotype (SASP) and exacerbating inflammation and metabolic disorders [9]. 4. The microenvironment of fat tissue is altered, leading to abnormal communication between stressed fat cells and immune cells, which amplifies inflammation [9]. 5. The vascular network within fat tissue deteriorates, causing dysfunction and contributing to hypoxia and inflammation [10]. Group 2: Weight Loss and Recovery - The research highlights that weight loss leads to a remarkable transformation in fat tissue, characterized by: 1. A "metabolic super-reboot," where fat cells regain and enhance their metabolic flexibility, improving insulin sensitivity [10]. 2. A significant reduction in inflammatory immune cells, restoring immune balance in fat tissue [10]. 3. The elimination of senescent cells, which may provide new insights into anti-aging therapies [10]. 4. Restoration of normal vascular function, improving blood supply and alleviating hypoxic conditions [10]. Group 3: Implications for Obesity Treatment - The study reveals concerning findings about "obesity memory," where certain immune cells retain a "memory" of the obese state, potentially leading to rapid weight regain after weight loss [11][12]. - This suggests that successful weight loss may require interventions targeting the mechanisms of inflammation memory to achieve long-term weight management [13]. - The research indicates a shift in obesity treatment strategies from simple weight loss to more complex approaches focused on "tissue reprogramming," offering hope for billions affected by obesity [14].

Core Viewpoint - The article discusses a groundbreaking study by Professor Katrin Svensson's team at Stanford University, which developed an AI system called "Peptide Predictor" that discovered 2,683 previously unknown bioactive peptides, potentially revolutionizing obesity treatment [6][8]. Group 1: AI and Drug Discovery - The AI model significantly enhances drug discovery by accurately predicting which prohormone fragments may have therapeutic potential, moving from a trial-and-error approach to a more precise method [8]. - The discovery of the BRP (BRINP2-related peptide) highlights the potential of AI in identifying effective obesity treatments, showcasing its ability to select promising candidates from a vast pool [10]. Group 2: BRP's Mechanism and Benefits - BRP demonstrated remarkable appetite suppression in animal studies, showing effects comparable to popular GLP-1 drugs, indicating its strong anti-appetite activity [10]. - The peptide also optimizes metabolic regulation, enhancing fat oxidation while maintaining stable oxygen consumption and carbon dioxide production, suggesting it primarily regulates appetite rather than basal metabolic rate [12][14]. - BRP's unique mechanism of action, which activates specific neurons in the hypothalamus, avoids common side effects associated with GLP-1 drugs, such as nausea and gastrointestinal discomfort [14]. Group 3: Future Prospects - The research team has initiated preclinical safety assessments for BRP and plans to conduct the first human trials in 2026, with hopes of bringing the drug to market by 2030 [17]. - The goal is to develop a safe and effective weight loss medication that respects the body's natural metabolic balance, representing a new direction in obesity drug development [17].