Core Viewpoint - The FDA has approved Rybelsus® as the only oral GLP-1 medication for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes, regardless of prior cardiovascular events, highlighting the need for treatment options beyond blood sugar control [2][3][5]. Group 1: FDA Approval and Clinical Evidence - Rybelsus® is now recognized as the only oral GLP-1 drug approved for both primary and secondary prevention of MACE in high-risk type 2 diabetes patients [5]. - The SOUL study aimed to evaluate the effectiveness of oral semaglutide 14mg combined with standard treatment in reducing MACE risk, with MACE defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke [5][6]. - In the study, 12.0% of patients receiving semaglutide experienced MACE events compared to 13.8% in the placebo group, demonstrating a hazard ratio of 0.86, indicating a 14% relative risk reduction over four years [6]. Group 2: Safety and Side Effects - The overall safety profile of oral semaglutide 14mg was consistent with previous studies, with serious adverse events (SAEs) occurring in 47.9% of the semaglutide group compared to 50.3% in the placebo group [8]. - The most common SAEs included heart disease and infections, with gastrointestinal issues being slightly more prevalent in the semaglutide group (5.0% vs. 4.4%) [8]. - Discontinuation due to adverse events occurred in 15.5% of the semaglutide group versus 11.6% in the placebo group, primarily due to gastrointestinal disorders and infections [8]. Group 3: Future Developments - The company has submitted a supplemental application to the FDA for a daily oral semaglutide formulation, Wegovy®, aimed at treating obesity, with results expected later this year [9].

Core Insights - The article challenges the prevailing notion that urban residents are more prone to obesity than rural residents, revealing that rural populations have experienced a faster increase in BMI over the past three decades [7][18]. Summary by Sections Urban vs. Rural Obesity - Obesity has been labeled as an "urban disease," attributed to easy access to high-calorie processed foods and a sedentary lifestyle in cities [7]. - A recent study published in *Nature* analyzed BMI trends from 1985 to 2017 across over 112 million adults in 200 countries, indicating a significant shift in understanding obesity risk [8][12]. BMI Trends - The average BMI for women globally increased from 22.6 to 24.7, while for men it rose from 22.2 to 24.4, translating to an average weight gain of 5 to 6 kg per person [12]. - Notably, rural populations have seen a BMI increase of 2.1 kg/m², compared to urban increases of 1.3 kg/m² for women and 1.6 kg/m² for men [15][16]. Factors Contributing to Rural Obesity - The study highlights that rural areas have become the primary drivers of global BMI increases, contributing over 50% of the global rise, with this figure reaching 80% in low- and middle-income countries [16][20]. - In China, rural men's BMI surged from 20.9 to 23.9, making it one of the fastest-growing obesity rates globally [18]. Misconceptions about Rural Life - Factors leading to increased weight in rural populations include lower income and education levels, limited access to fresh foods, and a lack of recreational facilities [20]. - The "urbanization" of rural lifestyles, characterized by improved food supply and increased consumption of ultra-processed foods, is also a significant factor [20]. Policy Implications - The findings suggest a need for countries to prioritize intervention strategies targeting rural populations, which have been overlooked in obesity research and policy-making [21].

Core Viewpoint - The article emphasizes the importance of maintaining a balanced and nutritious diet for individuals using GLP-1 medications for weight loss, highlighting that even with reduced food intake, nutritional needs must be met to avoid health issues [4][5][6]. Dietary Guidelines - New dietary guidelines suggest that women taking weight loss medications should consume 1,200 to 1,500 calories daily, while men should aim for 1,500 to 1,800 calories [10]. - Recommended protein intake is over 60 to 70 grams per day, with sources including legumes, seafood, lean meats, poultry, low-fat dairy, and eggs [10]. - Healthy carbohydrates should make up 45% to 65% of total energy intake, with added sugars limited to below 10%. Suggested sources include whole grains, nuts, seeds, fruits, vegetables, and dairy [10]. - Fat intake should account for 20% to 35% of energy, with saturated fat limited to below 10%. Recommended fats include nuts, seeds, avocados, plant oils, and fatty fish, while fried and high-fat foods should be avoided [10]. - Daily fiber intake recommendations are 21 to 25 grams for women and 30 to 38 grams for men, with fruits, vegetables, and whole grains as primary sources [10]. - Individuals should consume two to three liters of fluids daily, including water and low-calorie beverages, while limiting caffeine intake [11]. Nutritional Supplements - The guidelines recommend supplementation of multivitamins, calcium, and minerals to ensure adequate intake of micronutrients [12]. Professional Guidance - It is advised that healthcare professionals or nutritionists monitor the dietary intake of patients on weight loss medications to prevent nutritional deficiencies [13]. - A thorough nutritional assessment before and during treatment is deemed necessary to avoid nutrient deficiencies and excessive muscle loss [14].

Core Viewpoint - The article discusses the benefits of GLP-1 receptor agonists, such as semaglutide and tirzepatide, in weight loss without significant muscle mass loss, highlighting their positive impact on body composition and energy levels [4][6][10]. Group 1: Research Findings - A study published in JAMA indicates that patients using GLP-1 receptor agonists do not need to worry about excessive muscle loss during rapid weight loss [4]. - Semaglutide has been shown to increase the proportion of lean body mass relative to total weight, leading to higher muscle quality and potential energy expenditure at lower body weights [4][6]. - The relationship between fat-free mass (FFM) and skeletal muscle mass (SMM) ratios and overall weight loss is explored, suggesting that maintaining or slightly increasing muscle mass can enhance basal metabolic rate [6][7]. Group 2: Clinical Perspectives - Concerns regarding muscle loss from GLP-1 agonists are described as hypothetical, with no substantial evidence supporting these fears [9][10]. - Medical professionals report that patients generally do not express concerns about muscle loss, focusing instead on weight loss and overall health improvements [10]. - Recommendations for patients include engaging in strength training and increasing protein intake to preserve muscle mass during weight loss [10]. Group 3: Cautionary Notes - Caution is advised for elderly patients and those losing more than 25% of their body weight, as they may face risks related to muscle loss and bone density [11]. - Additional monitoring, such as body composition scans and blood tests, is suggested for patients experiencing significant weight loss to ensure safety and health [11].

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。 现代社会虽然极大丰富了人们的食物选择，但也让某些疾病变得更加常见，比如肥胖和糖尿病的发病率在过去几十年里迅速攀升。与1975年相 比，全球肥胖人数已经翻了两番。大众普遍认为，肥胖只是体内脂肪不断堆积、腰围逐渐变粗而已。然而，科学家们更关注的是：为什么一旦 肥胖，脂肪会如此迅速增加，甚至后来节食也很难减掉？ 最新发表在《自然-代谢》杂志上的研究指出，肥胖难以逆转的关键原因之一，其实在于脂肪组织的代谢功能受损。当摄入过多能量时，脂肪 细胞中的线粒体会出现障碍，导致身体难以通过ATP代谢和产热将多余能量消耗掉。 | Received: 17 May 2023 | | --- | 当然，这一观点并非首次被提出。此前的研究就曾发现，白色脂肪组织在长期扩大的过程中，会经历炎症反应、激素反应迟钝等一系列代谢变 化，同时线粒体也会受到损伤。这种损伤不仅导致能量消耗下降，还与 ...

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。 办公室一族注意了！每天久坐不动又管不住嘴的你，可能正在陷入"越胖越不想动"的恶性循环。最新一期Ce ll杂志带来突破性发现：餐 桌上常见的甜菜碱（be t a i ne），竟能模拟运动效果，让懒人们坐着也能获得运动带来的三大黄金效益——加速新陈代谢、抗击慢性炎 症、延缓衰老进程！ 这项研究犹如给"运动困难户"投下一剂强心针。甜菜碱作为纯天然营养素，能巧妙激活与运动相似的代谢通路。特别适合那些"办了健 身卡却总找借口"的拖延症患者，以及因体重过重导致运动受限的肥胖人群。现在起，不用汗流浃背也能享受部分运动红利，科学"躺 瘦"时代真的要来了！ ▍ 甜菜碱：科学界发现的"运动黑科技"，躺着也能享受健身效果？ 现代人总抱怨没时间运动，但科学告诉你：或许有一种方法，能让你"不运动"却享受运动的好处！最新研究发现，甜菜碱（be t a i ne） 可能是最接近"运动模拟物"的天然成分——它能在分子层面模拟运动效果，帮你改善代谢、抗炎、抗衰老，甚至保护心脑 ...

Core Insights - Kailera Therapeutics has completed a $600 million Series B financing to advance its KAI-9531 product into global Phase III clinical trials, following a previous $400 million Series A round, totaling $1 billion in funding [2] - KAI-9531 is a dual-target GLP-1/GIP receptor agonist, initially developed by HengRui Medicine, which licensed global rights (excluding Greater China) to Kailera [4] - Clinical trial results indicate that participants treated with KAI-9531 achieved an average weight loss of up to 17.7%, with 88% of participants losing at least 5% of their body weight [4][5] Financing and Development - The Series B financing was led by Bain Capital, emphasizing Kailera's strong position in the weight loss sector [2] - The total funding of $1 billion positions Kailera as a significant player in the weight loss market [2] Clinical Efficacy - In a Phase II trial published in July 2024, KAI-9531 demonstrated that 91.8% of participants lost at least 5% of their body weight, with an average weight reduction of 16.8% [5] - The safety profile of KAI-9531 aligns with existing GLP-1 treatments, with most adverse events being mild to moderate and gastrointestinal in nature [4][6] Competitive Landscape - The only currently approved GLP-1/GIP dual-target receptor agonist is Zepbound, which received FDA approval in November 2023, showcasing the competitive nature of the market [5] - Kailera is also developing two additional obesity treatment drugs, KAI-7535 and KAI-4729, to further enhance its pipeline [6]

Core Viewpoint - Eli Lilly's oral GLP-1 therapy orforglipron has demonstrated superior efficacy in treating type 2 diabetes compared to AstraZeneca's SGLT2 inhibitor Farxiga, achieving significant reductions in A1C levels and weight loss in recent trials [2][4]. Group 1: Clinical Trial Results - In the latest Phase III trial ACHIEVE-2, orforglipron was tested on 962 adult participants with type 2 diabetes who had inadequate blood sugar control after metformin. The study compared three doses of orforglipron against Farxiga, with the primary goal of demonstrating non-inferiority in A1C reduction after 40 weeks [2][4]. - All doses of orforglipron met the primary and all key secondary endpoints, significantly lowering A1C levels and promoting weight loss. Specifically, the 3 mg dose resulted in a 1.3% reduction in A1C, while the 12 mg and 36 mg doses achieved a 1.7% reduction. In contrast, Farxiga only resulted in a 0.8% reduction [4]. - Another late-stage study, ACHIEVE-5, also showed positive results for orforglipron compared to placebo in patients with insufficient blood sugar control who were using titrated insulin glargine. The 3 mg dose led to a 1.5% reduction in A1C, the 12 mg dose achieved a 2.1% reduction, and the 36 mg dose resulted in a 1.9% reduction, while placebo only saw a 0.8% reduction [4]. Group 2: Safety and Tolerability - The safety and tolerability of orforglipron in both studies were consistent with previous findings, with stable discontinuation rates. The most common adverse reactions were gastrointestinal symptoms, which were generally mild to moderate, and no liver safety issues were observed [4]. Group 3: Future Developments - Detailed data from the two studies will be presented at an upcoming medical conference. The final global registration study of the ACHIEVE program, ACHIEVE-4, is expected to be completed in the first quarter of 2026, paving the way for orforglipron's market application in type 2 diabetes [5]. - Additionally, the application for orforglipron's use in obesity treatment is set to be initiated by the end of this year [6].

Core Insights - The article discusses the rising trend of GLP-1 drugs, particularly semaglutide and tirzepatide, among Silicon Valley elites, who are using these medications not just for weight loss but also for enhancing cognitive function and overall lifestyle optimization [5][11][12]. Group 1: Usage and Perception - A survey indicated that 50.5% of respondents in the tech industry are using GLP-1 drugs, significantly higher than the general population [6]. - Users are adopting "micro-dosing" strategies to maintain lower doses of the medication, which they believe can provide benefits while minimizing side effects [8]. - Many tech professionals view GLP-1 drugs as tools for "biohacking," aiming to improve energy levels and cognitive performance during demanding work situations [11]. Group 2: Competitive Advantage - GLP-1 drugs, initially developed for diabetes treatment, are now being recognized for their potential benefits in weight management and cognitive enhancement [12]. - Users report significant lifestyle improvements, such as reduced cravings and better focus during meetings, which they attribute to the effects of GLP-1 medications [10][13]. - The trend is particularly strong among individuals seeking competitive advantages in their professional lives, with some users feeling empowered and more confident in their decision-making [11][13]. Group 3: Market Dynamics - Companies in the healthcare sector are increasingly focusing on GLP-1 drugs, with remote healthcare services expanding their offerings to include these medications [15]. - The rise of GLP-1 drugs has led to a shift in consumer habits, with companies like Hims and Noom integrating these medications into their business models [15][16]. - The article highlights the potential for significant market growth as more individuals seek out GLP-1 drugs for both weight management and overall health optimization [16].

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。 美国希望之城医学中心与加州大学洛杉矶分校的联合研究团队在《科学》期刊发表突破性发现。这项题为《随年龄增长出现的独特脂肪 前体细胞驱动活跃脂肪生成》的研究指出，中年时期内脏脂肪的异常堆积，源于一类特殊的脂肪干细胞突然活跃。这些"潜伏者"会随着 年龄增长被激活，像叛逆期的青少年般疯狂增殖，最终导致内脏脂肪组织不可逆的扩张。研究不仅解开了中年发福的生理密码，更为代 谢综合征等年龄相关疾病提供了全新解释维度。 当岁月的痕迹悄然爬上腰腹，许多中年人都会困惑：为何体重秤的数字与日俱增？那些曾经合身的西装裤为何逐渐变得紧绷？最新科学 研究揭示，这场"中年膨胀"的背后，竟是一场蓄谋已久的脂肪细胞叛乱。 值得注意的是，这种脂肪堆积机制与单纯的热量过剩截然不同。即便保持青年时期的饮食运动习惯，中年人仍可能遭遇这场无声的"腰 围革命"。科学家们通过追踪脂肪干细胞的分子特征发现，这些细胞会随着机体衰老获得独特的表观遗传标记，就像被装上定时炸弹， 在中年时期集中爆发增 ...