Core Viewpoint - The article discusses the usage, storage, dietary considerations, and potential side effects of the GLP-1 receptor agonist drug Semaglutide, emphasizing the importance of proper administration and nutrition for users [2][3][4][6]. Usage Guidelines - Initial dosage of Semaglutide should start at 0.25 mg weekly, gradually increasing as per medical advice, with a maximum single dose of 1 mg [2]. - Oral Semaglutide should be taken before breakfast with no more than 120 ml of water, and patients should wait at least 30 minutes before consuming food or other medications [2][5]. - The injectable form is administered subcutaneously once a week, with recommended sites being the abdomen, outer thigh, and upper arm [2][5]. Storage Conditions - Oral Semaglutide is more flexible in storage and does not require refrigeration, while unopened injectable Semaglutide must be stored in a refrigerator (2°C-8°C) and can be kept at room temperature (below 30°C) for up to 6 weeks after first use [3]. Monitoring and Side Effects - Regular blood sugar monitoring is essential during Semaglutide use, with necessary dosage adjustments made under medical supervision [4]. - Gastrointestinal side effects such as nausea, vomiting, and diarrhea may occur, particularly in the initial treatment phase, but often lessen over time [4]. Dietary Considerations - Users of Semaglutide should focus on nutrient-dense foods, ensuring adequate intake of quality protein, fiber, and hydration, while considering the potential for nutrient deficiencies due to reduced food intake [6][10]. - A balanced meal plate should include protein, vegetables, and starches, tailored to individual health conditions and preferences [9][10]. Foods to Avoid - High-fat foods, especially fried and heavily oil-based dishes, should be avoided as they may cause gastrointestinal discomfort [12]. - Foods high in trans fats and saturated fats, such as full-fat dairy and red meats, can exacerbate gastrointestinal issues and affect drug efficacy [12]. - High-sugar foods and refined carbohydrates should be limited to prevent blood sugar spikes, particularly for diabetic patients [14]. - Alcohol consumption should be minimized as it can aggravate digestive issues and increase the risk of hypoglycemia [15]. Positive Body Composition Changes - A study involving 241 patients showed that those who lost weight while using Semaglutide experienced positive changes in body composition, including reductions in visceral fat area and liver volume, which are beneficial for metabolic health [16][17].

Core Viewpoint - The article discusses a recent study published in *Science* that reveals the underlying biological mechanisms contributing to abdominal fat accumulation in middle-aged individuals, particularly focusing on a specific type of fat cell that becomes more active with age [5][10]. Group 1: Mechanisms of Fat Accumulation - The study indicates that the increase in abdominal fat in middle-aged individuals is primarily due to the generation of new fat cells rather than the enlargement of existing ones, challenging the previous belief that fat cell numbers remain constant after adulthood [7]. - Researchers found that a specific subgroup of fat precursor cells, known as CP-A, significantly increases in number and activity in middle-aged mice, accounting for 34.23% of the visceral white adipose tissue [8][10]. - The proliferation and differentiation capabilities of CP-A cells are four times greater than those of another type of precursor cell, CP-1, indicating that CP-A plays a crucial role in the accumulation of visceral fat in middle age [9]. Group 2: Role of LIFR in Fat Cell Generation - The study identifies LIFR (leukemia inhibitory factor receptor) as a key gene that is highly expressed in CP-A cells and is associated with aging and fat generation [12]. - Inhibition of LIFR using a specific inhibitor (EC359) resulted in a 60% reduction in fat generation from CP-A cells, while having minimal effect on CP-1 cells, highlighting the dependency of CP-A on LIFR signaling [15]. - The activation of the JAK-STAT3 signaling pathway by LIFR is crucial for the proliferation and fat-generating capabilities of CP-A cells, suggesting that targeting LIFR could be a potential strategy to mitigate abdominal fat accumulation in middle-aged individuals [15].

Core Viewpoint - The article discusses the significant clinical data from the PIONEER 11 and PIONEER 12 studies, which support the approval of semaglutide tablets (brand name: Ozempic) for treating type 2 diabetes (T2DM) in the Chinese population, highlighting its efficacy in blood sugar control and weight loss [5][6][17]. Group 1: PIONEER 11 Study - The PIONEER 11 study evaluated the efficacy and safety of semaglutide as a monotherapy in Chinese T2DM patients with poor dietary and exercise control, revealing differences in clinical profiles compared to Western populations [7][12]. - This study was a 26-week, randomized, double-blind, placebo-controlled trial involving 521 T2DM patients, with approximately 75% being from China. The primary endpoint was the change in HbA1c levels at week 26, and the secondary endpoint was weight change [8]. - Results showed that all doses of semaglutide (3mg, 7mg, 14mg) significantly reduced HbA1c levels compared to the placebo, with the 14mg group achieving a reduction of 1.6%. Additionally, the 7mg and 14mg groups experienced significant weight loss, with the 14mg group losing 3.0kg overall and 2.6kg in the Chinese subgroup [8][10]. Group 2: PIONEER 12 Study - The PIONEER 12 study assessed the combined effect of semaglutide and sitagliptin in T2DM patients stabilized on metformin, indicating potential differences in drug response between Chinese and Western populations [12][14]. - This study also lasted 26 weeks and included 1,441 patients, with around 75% from China. The primary and secondary endpoints were consistent with those of PIONEER 11 [13]. - Findings revealed that all doses of semaglutide significantly outperformed sitagliptin in reducing HbA1c levels, with the 14mg group showing a reduction of 1.6%. Weight loss was also significant, with the 14mg group losing 3.8kg overall and 3.4kg in the Chinese subgroup [14][16]. Group 3: Safety and Tolerability - Both PIONEER studies reported gastrointestinal adverse events as the most common side effects, which were mostly mild and transient. No severe hypoglycemic events were reported in either study [10][16]. - The completion rates for the trials were high, indicating good patient adherence and tolerability to the treatment [8][13]. Group 4: Conclusion - The 14mg dose of oral semaglutide demonstrated significant weight loss and blood sugar control in the Chinese population, suggesting it is well-suited for use in this demographic despite their lower baseline weight [17].

Core Viewpoint - Metsera's ultra-long-acting GLP-1 receptor agonist MET097 has entered the critical phase of global weight loss drug competition with its Phase 3 clinical trial registration, following its acquisition by Pfizer, indicating a strategic move in the metabolic disease sector [5][9]. Group 1: Clinical Trial Details - The VESPER-4 trial is a large-scale, randomized, controlled Phase 3 study involving 3,500 participants with obesity or overweight, expected to complete preliminary research by September 2027 [6][8]. - The trial will assess the efficacy and safety of MET097, administered via weekly subcutaneous injections, with the primary endpoint being weight reduction after 64 weeks of continuous treatment [7][8]. Group 2: Pharmacokinetics and Administration - MET097 has a half-life of 18 days, suggesting potential for monthly dosing regimens, which could enhance patient compliance and optimize real-world usage scenarios [9]. - Despite its potential for longer dosing intervals, the initial Phase 3 trial will utilize a weekly administration schedule, reflecting Pfizer's balance between regulatory risks and commercial aggressiveness [10]. Group 3: Competitive Landscape - Pfizer's acquisition of Metsera and the development of MET097 represent a strategic entry into the GLP-1 weight loss market, where competitors like Novo Nordisk and Eli Lilly have established significant product and market barriers [10].

肥胖世界ObesityWorld . 以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 减肥道理人人都懂，"少吃多动"四字真言简单明了。然而实践起来却难如登天，改变生活方式需要决心、毅力、时间、金钱缺一不可。至于那 些激进医疗手段，多数人又没到非用不可的地步，吃药手术既花钱又伤身。 有没有谁能替我吃掉那些热量，让我不费力就变瘦呢？（做梦谁不会呀） 别笑，这还真不是痴人说梦！近期《细胞·代谢》杂志刊登了日本RIKEN研究所科研团队的一项突破性研究，提出了一种借助肠道菌群"代 吃"的减重创新思路。 研究人员发现，乙酰纤维素(AceCel)能有效重塑肠道菌群组成与功能，特别是显著增强了肠道多形拟杆菌(Bacteroides thetaiotaomicron)的碳 水化合物代谢能力，大量消耗原本会被人体吸收的单糖。 《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。 研究者发现，乙酰纤维素组小鼠肠道中大多数二糖和单糖含量显著降低。在乙酰纤维素存在下，这些本应被小鼠肠道吸收的碳水化合物更多地 被"转移"给 ...

Core Viewpoint - The article discusses the evolution of GLP-1 receptor agonists, highlighting the transition from semaglutide to the next-generation drugs like tirzepatide and retatrutide, which show enhanced efficacy in weight loss and metabolic management [5][8][10]. Group 1: Semaglutide and Tirzepatide - Semaglutide, originally developed for type 2 diabetes, has gained popularity as a weight loss drug, demonstrating significant reductions in blood sugar and body weight, while also showing cardiovascular and renal protective effects [5]. - Tirzepatide, known as a "second-generation miracle drug," is the first GLP-1/GIP dual agonist, offering amplified effects on weight loss and lipid metabolism, particularly beneficial for high-risk cardiovascular patients [5][8]. - Clinical trials indicate that tirzepatide may provide renal protection comparable to or better than semaglutide, establishing it as a new standard in metabolic treatment [5][8]. Group 2: Retatrutide - Retatrutide, currently in Phase III clinical trials, activates three metabolic pathways: GLP-1, GIP, and glucagon receptors, leading to significant improvements in weight loss, blood sugar control, and lipid profiles [6][8]. - In obese populations, retatrutide's weight loss results are approaching those of surgical interventions, and it shows superior reductions in HbA1c levels among type 2 diabetes patients [8][9]. - Preliminary studies suggest that retatrutide may not impose additional burdens on renal function and could potentially offer renal benefits through improved metabolic states [9]. Group 3: Future Implications - The advancements from semaglutide to tirzepatide and now to retatrutide signify a fundamental shift in metabolic disease treatment, moving beyond mere glucose control or weight loss to a comprehensive approach addressing energy metabolism, lipid metabolism, and cardiovascular risks [9][10]. - If retatrutide fulfills its potential in ongoing trials, it could herald a new era in the treatment of metabolic diseases, combining weight loss, blood sugar reduction, and lipid management in one therapy [10].

Core Viewpoint - The article discusses the discovery and potential of a new anti-obesity peptide called BRP (BRINP2-related peptide), which shows promise in reducing food intake and body weight without causing adverse effects, marking a significant advancement in obesity treatment [7][12][20]. Group 1: Discovery of BRP - BRP was identified by a research team at Stanford University using artificial intelligence, demonstrating its effectiveness in reducing food intake in mouse and pig models without causing nausea [7][12]. - The peptide is derived from the BRINP2 protein and consists of 12 amino acids, showing a significant increase in Fos expression in neuronal cells, indicating its biological activity [12][13]. Group 2: Mechanism of Action - BRP operates through the CREB-FOS signaling pathway in the central nervous system, specifically activating neurons in the hypothalamus, which is crucial for appetite regulation [20][22]. - The peptide's action is independent of leptin, GLP-1 receptor, and melanocortin 4 receptor signaling pathways, highlighting its unique mechanism [7][20]. Group 3: Efficacy and Safety - In studies, BRP significantly reduced food intake in mice, with a dose of 5 mg/kg leading to a notable decrease in consumption, while a higher dose of 20 mg/kg nearly completely suppressed food intake [12][13]. - Importantly, BRP did not induce adverse reactions such as nausea or aversion, which are common side effects associated with other weight loss treatments [14][20]. Group 4: Comparative Effectiveness - In a pig model, BRP demonstrated a 50% reduction in food intake within one hour of administration, comparable to the effects of GLP-1 receptor agonists like liraglutide [15][17]. - Over a 14-day treatment period in obese mice, BRP led to a significant reduction in body weight and improved glucose and insulin tolerance, primarily through fat loss rather than muscle mass reduction [17][20]. Group 5: Future Implications - The research presents BRP as a potential therapeutic agent for obesity, offering a new avenue for treatment that may be free from the side effects associated with current obesity medications [22].

Core Insights - The article highlights the significant advancements in weight loss medications, particularly focusing on the role of GLP-1R agonists like semaglutide and the emerging interest in GIPR as a target for obesity treatment [5][8]. Group 1: Mechanisms of Action - Semaglutide, a GLP-1R agonist, has revolutionized weight loss by stimulating insulin secretion, regulating metabolism, and suppressing appetite [5]. - GIPR, another member of the incretin hormone family, has shown perplexing effects where both its activation and inhibition can lead to weight loss, indicating a complex underlying mechanism [5][8]. - Recent studies reveal that GIPR agonists and antagonists activate different neuronal pathways in the central nervous system, with agonists primarily affecting GABAergic neurons and antagonists relying on GLP-1R signaling [5][11]. Group 2: New Drug Developments - The dual-target weight loss drug tirzepatide, which activates both GIPR and GLP-1R, has demonstrated significant weight loss effects, surpassing the sum of individual effects [8]. - The GIPR-Ab/GLP-1 peptide antibody conjugate developed by Amgen requires the presence of both GIPR and GLP-1R in the brain to exert its anti-obesity effects, confirming the findings of the Gutgesell team [6][11]. - AMG133, a bispecific hybrid antibody that activates GLP-1R and antagonizes GIPR, is currently in Phase 2 clinical trials and shows promise in appetite suppression and weight loss [8][11]. Group 3: Implications for Future Research - The understanding of GIPR and GLP-1R mechanisms opens new avenues for developing more precise and effective weight loss therapies [11]. - The contrasting transcriptional responses induced by GIPR agonists and antagonists in the brain suggest potential for targeted therapeutic strategies in obesity management [11].

整理 | GLP1减重宝典内容团队 替尔泊肽是一种基于GIP序列改良的分子，它增加了GLP-1的活性，其GIP活性大约是 GLP-1的10倍。这种结合GLP-1和GIP的双靶点 药物，通过两者的互补和协同作用，展现出显著的疗效。 首先，GLP-1可能会引起恶心和呕吐等中枢神经系统的副作用。而GIP在降低食欲的同时，能够减轻这些不适症状，从而在一定程度上 抵消了GLP-1的副作用。 其次，GIP和GLP-1在胰腺的作用也有所不同。GIP不仅能调节糖代谢，还能调节脂代谢，这对于控制血糖和血脂都非常重要。此外， GIP在皮下脂肪组织中的表达量很高，这意味着它在脂肪代谢中扮演着重要角色。GIP有助于促进体内脂肪的再平衡和再分布，提高脂 肪组织的储存能力，同时减少异常脂肪堆积，这是含有GIP的双靶点药物相较于单靶点药物的一个显著优势。 点击关注，追踪最新GLP-1资讯 通过这种创新的分子设计，替尔泊肽不仅提高了治疗效果，还减少了可能的副作用，为糖尿病患者提供了一种新的治疗选择。 在代谢性疾病的研究领域，继GLP-1（胰高糖素样肽-1）单靶点药物之后，GLP-1/GIP（葡萄糖依赖性促胰岛素多肽）双靶点药物因其 在胰腺、 ...

Core Viewpoint - The article discusses the effectiveness of Tirzepatide, a dual agonist of GIP and GLP-1 receptors, in weight loss, highlighting its clinical trial results and personal success stories from various individuals who have used the drug for weight management [4][6][12]. Group 1: Clinical Research Findings - Tirzepatide has shown significant weight loss results comparable to bariatric surgery in a clinical trial involving 2,539 adults with obesity-related complications, where participants lost an average of 16.1 kg, 22.2 kg, and 23.6 kg in different dosage groups over 72 weeks, compared to a 2.4 kg loss in the placebo group [4]. Group 2: Personal Success Stories - Dan Yongping reported a weight loss of 15 pounds (approximately 13.6 kg) after using Tirzepatide for two and a half months, noting improvements in his blood lipid levels without significant side effects [6]. - Whoopi Goldberg shared her experience of losing nearly double her weight since starting Tirzepatide, emphasizing its positive impact on her health [7]. - Lauren Manzo, after using Tirzepatide, lost 30 pounds (approximately 27.2 kg) and stated that the drug was more effective than other weight loss methods, even better than weight loss surgery [11]. - Charles Barkley mentioned a weight loss of 65 pounds (approximately 58.9 kg) while using Tirzepatide, highlighting the challenges he faced with traditional weight loss methods [12][14].