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。 中国糖尿病防治形势严峻，不仅存在1 . 4亿确诊患者，更令人担忧的是约5亿人正处于糖尿病前期状态。临床数据显示，若不采取有效干 预措施，这些糖尿病前期人群3 0年后患病风险将飙升至9 5. 9%。糖尿病前期作为糖尿病发展的关键过渡阶段，主要表现为空腹血糖异常 （IFG）、糖耐量降低（IGT）以及糖化血红蛋白（HbA1 c）水平波动等特征。虽然健康生活方式对预防糖尿病的作用已广为人知，但 其对逆转糖尿病前期的效果却存在显著个体差异。国际权威期刊《Di a b e t e s & Me t a b o li c Sy n d r ome : Cli n i c a l Re s e a r c h & Re v i ews》 最新发表的重磅综述系统性地解答了这一关键问题，研究指出干预效果与个体特征密切相关。 这项研究深入分析了不同干预措施对各类糖尿病前期人群的差异化影响，强调个性化干预的重要性。研究团队通过系统回顾大量临床数 据发现，虽然生活方式 ...

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。 "被确诊为糖尿病的那一天，我以为此生都得依靠药物维持生命。可当我成功减重25公斤后，医生却告诉我：你已经不是糖尿病人了。"这是英国 患者Isobel Murray的亲身经历，也是《柳叶刀》系列研究揭示的科学奇迹——科学减重让近一半2型糖尿病患者实现彻底缓解。本文将结合全球 权威数据，带你深入探讨糖尿病逆转背后隐藏的科学奥秘。 01 • 《柳叶刀》三大里程碑研究 1. 2023年Meta分析：减重幅度越大，缓解效果越显著 《柳叶刀·糖尿病与内分泌学》最新发表的研究（DOI:10.1016/S2213- 8587(23)00134-X），汇总了全球32项临床试验数据，得出以下结论： 1. 体重下降5%，糖尿病风险降低58%（空腹血糖平均下降0.8mmol/L）； 2. 体重减少10%，胰岛素敏感性提升高达70%； 2. DiRECT研究：饮食管理重塑糖尿病走向 ...

Core Viewpoint - Weight loss is not equivalent to fat loss; the ideal scenario is to reduce fat while preserving muscle mass, as muscle helps maintain basal metabolic rate and body shape [2][4]. Group 1: Weight Loss Mechanism - Over-restrictive dieting can lead to muscle loss primarily due to nutritional deficiencies, as the body prioritizes muscle tissue for energy when caloric intake is significantly low [4]. - Hormonal changes, such as increased cortisol and decreased testosterone levels, can further promote muscle breakdown and inhibit muscle synthesis [4]. - Long-term low-calorie intake may reduce metabolic rate, making it harder to maintain muscle mass [4]. Group 2: GLP-1 Medications - GLP-1 receptor agonists (GLP-1 RAs) mimic the action of the natural hormone GLP-1, which plays a crucial role in blood sugar regulation [5]. - These medications promote insulin secretion in a glucose-dependent manner, helping to lower postprandial blood sugar levels [7]. - GLP-1 RAs inhibit glucagon secretion, which typically raises blood sugar levels when they are low, thus aiding in blood sugar control [7]. - They also delay gastric emptying, reducing the speed at which food enters the small intestine, which helps manage post-meal blood sugar spikes [8]. - Additionally, GLP-1 RAs act on the brain's appetite regulation centers to suppress appetite, aiding in weight management [9]. - Long-term use of GLP-1 RAs may improve or protect pancreatic beta-cell function, which is particularly important for type 2 diabetes patients [10]. Group 3: Weight Loss Results - In the PIONEER PLUS phase 3 study, participants treated with oral semaglutide for 68 weeks lost an average of 9.2 kg (9.54%) and 7.0 kg (7.26%) at doses of 50 mg and 25 mg, respectively [11]. - The latest OASIS 1 study reported that participants in the 50 mg group lost an average of 18.34 kg (17.4%), indicating an improvement in weight loss efficacy [12].

Core Viewpoint - A new study published in the Annals of Internal Medicine emphasizes the need for a revised Body Mass Index (BMI) standard for Asian populations due to unique obesity characteristics that increase health risks even at lower BMI levels [4][5]. Group 1: Research Findings - The research led by Dr. Simar S. Bajaj indicates that Asians are prone to central obesity, which poses higher health risks such as type 2 diabetes and cardiovascular diseases, even with a lower BMI [5]. - The study advocates for the establishment of specific BMI thresholds for Asian populations, highlighting the necessity for further research to determine exact values [5]. - Current global obesity diagnostic standards may undergo significant changes based on these findings, as the study suggests that existing standards do not adequately reflect the health risks faced by Asians [5]. Group 2: Current Standards and Discrepancies - The World Health Organization (WHO) has not set a unified standard for obesity in Asia, allowing countries to adjust their standards based on local health risks, leading to significant discrepancies among countries like India and China [7]. - In the United States, there is ongoing debate regarding the classification of Asian populations under a single BMI standard, with some organizations proposing adjustments to the BMI thresholds for Asian individuals [8][9]. - The American Diabetes Association (ADA) and the American Society for Metabolic and Bariatric Surgery (ASMBS) have suggested lowering the BMI screening thresholds for Asians to 23 kg/m² and 27.5 kg/m² respectively [9]. Group 3: Implications for Future Research - Recent studies indicate that different Asian ethnic groups exhibit varying diabetes risk levels at the same BMI, challenging the notion of a homogeneous Asian population regarding obesity risk [11]. - A large-scale study involving 147,000 participants confirmed that the BMI threshold for diabetes risk differs significantly among ethnic groups, necessitating a more nuanced approach to obesity standards [11]. - The research highlights the importance of incorporating additional metrics such as waist circumference and waist-to-hip ratio, especially for populations with a BMI of 23 or higher, to enhance the precision of obesity assessments [11].

Core Viewpoint - The article discusses a groundbreaking study revealing a new physiological phenomenon where the central nervous system regulates intestinal nutrient absorption, particularly fat, through the vagus nerve, with implications for obesity and metabolic disease treatment [10]. Group 1: Research Findings - The study identifies that the Phox2b neurons in the dorsal motor nucleus of the vagus (DMV) can significantly influence fat absorption in the intestines, leading to weight loss in mice on a high-fat diet [7]. - The research team discovered that the herbal compound puerarin can reduce the activity of Phox2b DMV neurons, promoting fat excretion and aiding weight loss [8]. - The study confirmed that the GABRA1 protein, a subunit of the GABA A receptor, is a key target for puerarin, which enhances chloride ion influx and inhibits DMV neuron activity [9]. Group 2: Mechanism of Action - The research demonstrated that the inhibition of DMV neurons or intervention with puerarin leads to a significant reduction in the length of intestinal microvilli, which is crucial for fat absorption [9]. - The study utilized advanced techniques such as pharmacogenetics, neurophysiology, and structural biology to elucidate the molecular mechanisms by which puerarin exerts its effects [10]. Group 3: Implications for Future Research - The findings open new avenues for drug development targeting obesity and metabolic diseases by modulating the central regulation of intestinal fat absorption [10]. - The research highlights the potential for further exploration of the brain-gut signaling pathways, which could lead to innovative therapeutic strategies for managing obesity [10].

Core Viewpoint - The article discusses the promising results of the oral small molecule GLP-1 receptor agonist MDR-001 developed by Derui Zhiya, which shows significant weight loss in overweight or obese individuals after a 12-week treatment period [2][3]. Group 1: Study Results - The study included 24 adult participants, randomly assigned in a 2:1 ratio to receive either MDR-001 or a placebo for 12 weeks [3]. - The MDR-001 group experienced an average weight loss of 8.9%, compared to 0.6% in the placebo group, resulting in a net weight loss of 8.3% after adjusting for placebo effects [2][3]. - 93.8% of participants in the MDR-001 group achieved at least a 5% weight loss, and 37.5% achieved at least a 10% weight loss, with beneficial changes observed in various metabolic and cardiovascular indicators [3]. Group 2: Safety and Tolerability - The overall safety and tolerability of MDR-001 were reported to be good, with no serious adverse events noted during the trial [3]. - The most common side effects were gastrointestinal reactions, which were mostly mild to moderate and manageable [3]. Group 3: Comparison with Previous Studies - The article highlights that in a previous Phase IIb study using a "twice daily" (BID) dosing regimen, a weight loss of 10.3% was reported over 24 weeks, indicating that the current "once daily" (QD) regimen provides new evidence for dosing frequency optimization and long-term validation [3].

整理 | GLP1减重宝典内容团队 近年来，GLP-1受体激动剂（GLP-1RA）显著改变了肥胖管理格局，但"停药即反弹"的现实挑战同样显著。来自丹麦的一项随机对照研 究延伸随访显示：与单用药物相比，将监督运动纳入治疗与停药过渡期，能在一年后显著改善体重与体成分维持。这一发现为临床决策 与患者长期管理提供了更具操作性的路径。 ▍ 研究设计与方法概览 试验纳入18–65岁肥胖成人（BMI 32–43 kg/m²），整体分三阶段推进： 停治随访（52–104周）：全部干预在第52周终止，于第104周评估体重、体脂等结局。 主要终点为从随机化（第0周）至停药后一年（第104周）的体重变化，次要终点为体脂百分比变化。共有109名完成治疗者参加了停药 一年后的评估。 ▍ 主要发现与证据 联合方案的持久优势：与单用利拉鲁肽相比，"监督运动+利拉鲁肽"在停药一年后体重更低（约−5.1 kg，具有统计学意义），体脂百分 比亦显著下降（约−2.3 个百分点）。达成并维持≥10%初始体重减轻的比例，联合组显著高于单药与安慰剂。 运动带来的"后劲"：停药后一年，单用利拉鲁肽的体重回升幅度高于监督运动组（约+6.0 kg的差异），也 ...

Core Viewpoint - The article discusses the recent announcement by Borui Pharmaceutical regarding its plan to issue H-shares and list on the Hong Kong Stock Exchange, while emphasizing the company's commitment to balancing shareholder interests with market conditions [2]. Product Portfolio - Borui Pharmaceutical has a diverse product line covering multiple therapeutic areas, including metabolism, antiviral, antifungal, immunosuppressive, respiratory, and oncology. Key innovative drugs in the metabolism category include BGM0504 and BGM1812, while antiviral products include Entecavir and Oseltamivir. The antifungal category features Caspofungin and Micafungin Sodium, among others [3]. Financial Performance and R&D Progress - In the first half of 2025, Borui Pharmaceutical reported a revenue of 537 million yuan and a net profit of 14.36 million yuan after deducting non-recurring items. The company is focusing on multi-target metabolic drugs containing GLP-1 and exploring new administration routes beyond injections for chronic metabolic diseases. The self-developed peptide-based hypoglycemic drug BGM0504, a dual receptor agonist for GLP-1 and GIP, shows potential in controlling blood sugar, weight loss, and treating non-alcoholic fatty liver disease (NASH). Currently, BGM0504 has completed patient enrollment for phase III clinical trials in China for both type 2 diabetes and weight loss indications, with progress being reported as smooth [5]. Industry Engagement - The "GLP-1 Club" has established a network of hundreds of professionals, providing a platform for industry insights and discussions related to the GLP-1 drug development and its applications in weight loss and diabetes management [9]. GLP-1 Drug Overview - GLP-1 (Glucagon-like peptide-1) is a hormone produced by intestinal L cells, classified as an incretin. GLP-1 receptor agonists are a new class of hypoglycemic drugs that enhance insulin secretion in a glucose-dependent manner, suppress glucagon secretion, and delay gastric emptying, leading to reduced food intake and lower blood sugar levels [13].

Core Viewpoint - The article discusses a recent study published in *Nature Metabolism* by a team from Shanghai Jiao Tong University, which demonstrates that resistant starch (RS) can significantly aid overweight or obese individuals in weight loss and improving metabolic health through modulation of gut microbiota and metabolic pathways [6][8]. Group 1: Research Highlights - The study integrates microbiome and metabolomics data to comprehensively assess the impact of resistant starch on gut microbiota structure and human metabolism [6]. - It employs a randomized, placebo-controlled crossover trial design, enhancing the reliability of results by minimizing confounding variables [6]. - The research reveals that resistant starch affects bile acid metabolism, reduces inflammation, repairs gut barriers, and inhibits lipid absorption, providing a new theoretical basis for obesity prevention and treatment [6][8]. Group 2: Study Methodology - The study included participants aged 18 to 55 years, classified as overweight or obese (BMI ≥ 24 kg/m²), and excluded those with acute diseases or recent antibiotic use [9]. - A randomized controlled crossover design was used to evaluate the effects of resistant starch on weight control and insulin resistance, combined with metagenomic and metabolomic techniques to analyze gut microbiota changes [10]. Group 3: Key Findings - The intervention with resistant starch resulted in significant weight loss, reduced fat mass, and improved insulin sensitivity among 37 overweight or obese participants over an 8-week period [11]. - Resistant starch increased the abundance of beneficial bacteria such as *Bifidobacterium*, enhancing gut barrier function and reducing inflammation [11][13]. - In animal models, the transplantation of gut microbiota from resistant starch-fed humans led to lower body weight and fat mass, indicating the effectiveness of RS-modulated gut microbiota in weight management [16]. Group 4: Mechanisms of Action - The study found that resistant starch-induced gut microbiota changes lowered systemic inflammation markers and improved gut barrier integrity, which is crucial for managing obesity-related chronic inflammation [18][19]. - The increase in *Bifidobacterium adolescentis* was closely linked to the alleviation of abdominal obesity, suggesting its potential role in metabolic health [21].

Core Viewpoint - The article emphasizes the critical role of managing prediabetes and obesity in preventing the progression to diabetes and cardiovascular diseases, highlighting the effectiveness of the drug Semaglutide (weight loss version) in improving health outcomes for overweight and prediabetic patients [5][6][20]. Group 1: Prediabetes and Health Risks - Prediabetes is a significant health warning signal, with 5%-10% of patients progressing to diabetes annually, and it is associated with increased cardiovascular risks [5][8]. - Meta-analysis shows that prediabetic patients have higher all-cause mortality and cardiovascular event rates compared to those with normal blood sugar levels [8][26]. Group 2: Obesity as a Risk Factor - There is a strong positive correlation between obesity and the risk of prediabetes, with risk increasing significantly as BMI rises: 25% increase for BMI 25.0-29.9 kg/m² and 184% for BMI ≥40 kg/m² [9][11]. - The 2023 Expert Consensus on Diabetes Prediabetes Intervention emphasizes weight management as a core strategy to prevent the progression of prediabetes [9][11]. Group 3: Semaglutide's Impact - The SELECT study demonstrated that Semaglutide (weight loss version) significantly reduces the risk of major cardiovascular adverse events (MACE) by 20% compared to placebo [17][18]. - The drug also shows remarkable effects on blood sugar control, with nearly 70% of patients achieving normal blood sugar levels, far exceeding the placebo group [18][20]. Group 4: Future Outlook - There is optimism that more prediabetic patients will receive early intervention, leading to improved long-term outcomes for overweight and obese individuals [21][22]. - The treatment of metabolic diseases is expected to enter a new era of precision and individualization [22].