整理 | GLP1减重宝典内容团队 司美格鲁肽、替尔泊肽等类似的减肥药已成为世界上最受欢迎的药物之一。但也有大批人停止服用它们。根据一项行业分析， 2021 年，美国约有三分之二开始服用此类药物（称为 GLP-1 激动剂）的人在一年内停止使用它们。 研究显示，当人们停止服用 GLP-1 激动剂时，一些人恢复了一部分体重。 身体自然会试图保持自己的体重点，肥胖专家 Arya Sharma 把这种拉力比作绷紧的橡皮筋。 如果你服用药物来改变你的生理机能，"橡皮筋的张力就会小很多"，他解释道。"但是当我停止服用药物时，这种张力就会再次出现"， Sharma说，他现居柏林，为几家对肥胖感兴趣的公司提供兼职咨询服务。 研究人员和临床医生通常将 GLP-1 激动剂视为终身治疗。 但无数因素可能会 迫使 人们停止服药。人们可能会失去支付昂贵药物的手 段、经历严重的副作用、受到持续短缺的影响或被提供有限期限的处方。 随着肥胖人数不断增加——世界卫生组织估计，目前肥胖人数超过 10 亿，占世界人口的八分之一——研究人员一直在回答一些关键问 题： ▍ 当人们停止服用司美格鲁肽后，体重和健康状况会发生什么变化？ Ozempic 和 ...

Core Viewpoint - The article discusses the gender differences in the usage of GLP-1 medications for weight loss, highlighting that women are more likely to use these drugs compared to men, who prefer dietary and exercise changes [4][5][6]. Group 1: Gender Differences in Usage - Women are more proactive in considering GLP-1 medications like semaglutide for weight loss, while men tend to delay this consideration [5] - A significant majority of prescriptions for Wegovy (78%) and Zepbound (76%) are issued to female patients, despite similar obesity rates between genders (43% for men and 42% for women) [6] - Cultural expectations contribute to the lower usage of weight loss medications among men, as societal norms often allow them to be less concerned about obesity [7] Group 2: Interest in Broader Health Benefits - Men show increasing interest in semaglutide for its cardiovascular, kidney disease, and alcohol use disorder benefits, which may shift the gender balance in usage [8] - The approval of Wegovy for reducing heart disease risk and the anticipated approval of Zepbound for sleep apnea may enhance male interest in these medications [8] - The perception of these drugs as health therapies rather than merely cosmetic solutions is gaining traction among male patients [8] Group 3: Celebrity Influence - High-profile figures like Boris Johnson and Elon Musk have publicly shared their positive experiences with semaglutide, potentially influencing public perception and acceptance of the drug among men [9][13] - Johnson noted a significant decrease in appetite and food intake after starting semaglutide, while Musk reported a weight loss of 30 pounds (approximately 13.6 kg) with the help of the drug [11][13] - Other celebrities, such as Jon Gosselin, have also reported substantial weight loss results, further promoting the drug's effectiveness [15]

Core Viewpoint - GLP-1 agonists, such as semaglutide and tirzepatide, are popular weight loss medications, but a significant number of users discontinue their use within a year due to various factors, including cost, side effects, and prescription limitations [5][7]. Group 1: Impact of Discontinuation - A study indicated that approximately two-thirds of individuals who started using GLP-1 agonists in the U.S. stopped within a year [5]. - Upon discontinuation, many individuals experience weight regain, with studies showing that those who switched to a placebo regained nearly 7% of their weight after 11 months [12]. - An observational study found that 44% of individuals who stopped semaglutide regained at least 25% of their weight within a year [12]. Group 2: Health Risks Associated with Weight Regain - Discontinuation of semaglutide not only leads to weight regain but also a resurgence of health risks, including increased blood pressure, blood sugar, and cholesterol levels [13]. - Abdominal fat, which is linked to metabolic issues like heart disease and insulin resistance, tends to rebound after stopping the medication [13]. Group 3: Recommendations for Discontinuation - Gradual tapering off the medication rather than abrupt cessation may help mitigate rebound hunger and weight gain [14]. - Continuous monitoring of appetite and weight is advised for those who choose to stop the medication [14]. - Lifestyle changes, including diet and exercise, should be maintained even after discontinuation to help manage weight [15]. Group 4: Optimal Dosing Strategies - Research presented at the European Obesity Congress indicated that starting patients on the lowest effective dose of semaglutide and only increasing it when necessary can lead to significant weight loss while minimizing side effects [17]. - In a study, participants lost an average of 14.9 kg over 76 weeks while maintaining a low dose of semaglutide [17]. Group 5: Efficacy of Lower Doses - Another study demonstrated that a weekly dose of 0.5 mg of semaglutide resulted in an approximate 11% weight loss among participants [19].

Core Insights - The weight loss drug sector is experiencing significant activity, highlighted by Novo Nordisk's strong sales performance and strategic partnerships in the industry [2][3][5] Company Developments - Novo Nordisk reported a sales figure of 1127.56 billion Danish Krone (approximately 16.63 billion USD) for semaglutide in the first half of the year, accounting for 73% of its total revenue, with the weight loss version Wegovy generating 368.88 billion Danish Krone (54.41 billion USD), a 78% year-over-year increase [2] - BoRui Pharmaceutical's stock reached a new high of 114 CNY per share following the announcement of a partnership with China Resources Sanjiu to co-develop its weight loss drug BGM0504, with milestone payments potentially reaching 280 million CNY [3][4] - BoRui Pharmaceutical clarified that the 280 million CNY is not a business development fee but a milestone payment based on clinical progress and regulatory approvals, which they consider a fair price [4] Industry Trends - Pfizer announced the discontinuation of its last GLP-1 agonist, PF-06954522, marking the third GLP-1 candidate it has abandoned, citing a strategic assessment of the competitive landscape rather than safety issues [5] - The weight loss market remains highly attractive, with semaglutide and tirzepatide setting high entry barriers due to their established market presence and ongoing data improvements [6]

Core Insights - The weight loss drug sector is experiencing significant activity, highlighted by Novo Nordisk's strong sales performance and strategic partnerships in the industry [1][2]. Group 1: Company Performance - Novo Nordisk reported a sales figure of 1127.56 billion Danish Krone (approximately 16.63 billion USD) for semaglutide in the first half of the year, accounting for 73% of its total revenue [1]. - The sales of the weight loss version Wegovy reached 368.88 billion Danish Krone (54.41 billion USD), marking a year-on-year growth of 78% [1]. - BoRui Pharmaceutical's stock hit a record high of 114 CNY, with a market capitalization of 48.196 billion CNY, following the announcement of a partnership with China Resources Sanjiu for the development of its weight loss pipeline [1][2]. Group 2: Strategic Partnerships - BoRui Pharmaceutical announced the authorization of its product BGM0504 to China Resources Sanjiu, with milestone payments potentially reaching 280 million CNY [2]. - The collaboration allows BoRui to retain patent rights while leveraging China Resources Sanjiu's strengths in commercialization and market access [2][3]. Group 3: Market Dynamics - Pfizer announced the discontinuation of its last GLP-1 agonist, PF-06954522, marking the third GLP-1 candidate it has abandoned [4][5]. - The decision to halt development was based on an assessment of clinical trial data and the competitive landscape in the GLP-1 sector, rather than safety issues [4][5]. - The weight loss market remains attractive, with Novo Nordisk's semaglutide and Eli Lilly's tirzepatide leading the way, raising the competitive barriers for new entrants [5].

Core Viewpoint - Semaglutide, marketed as Ozempic, is emerging as a groundbreaking drug with potential to treat multiple diseases beyond diabetes, including obesity, cardiovascular issues, and possibly neurodegenerative diseases like Alzheimer's [2][5][10]. Group 1: Therapeutic Potential - Semaglutide has shown the ability to reduce the risk of heart attacks and strokes by nearly 20% in patients using Wegovy, a weight-loss version of Ozempic [2]. - Research indicates that semaglutide can lower the risk of kidney failure and mortality in diabetic patients over a three-year trial [2]. - The drug has also been linked to improvements in mental health, showing positive effects on depression and anxiety [2]. Group 2: Mechanisms of Action - The mechanisms behind semaglutide's effectiveness are still being explored, but it is known to influence brain reward pathways and inflammation [3]. - Semaglutide mimics the natural hormone GLP-1, which helps lower blood sugar levels and affects appetite regulation by signaling the pancreas to release insulin and slowing gastric emptying [5]. - The drug may also alter gut microbiota, promoting a healthier metabolism [5]. Group 3: Broader Health Benefits - Weight loss from semaglutide use is associated with improved fertility and overall organ health, as even slight weight reductions can benefit various bodily functions [6]. - Semaglutide has demonstrated anti-inflammatory properties, which may contribute to its effectiveness in treating cardiovascular diseases and other inflammation-related conditions [7][9]. - The drug has shown promise in treating conditions like asthma, non-alcoholic fatty liver disease, arthritis, and psoriasis due to its anti-inflammatory effects [9]. Group 4: Alzheimer's Disease Research - Studies indicate that semaglutide may reduce brain atrophy by 50% and slow cognitive decline by 18% in Alzheimer's patients compared to placebo [10]. - A significant study found that semaglutide use was associated with a 70% reduction in the risk of developing Alzheimer's among diabetic patients [10]. - Ongoing trials are evaluating the oral version of semaglutide for early Alzheimer's treatment, highlighting its potential multi-faceted approach to addressing the disease [10].

Core Insights - The 85th American Diabetes Association (ADA) conference showcased innovative metabolic drugs, particularly focusing on weight loss medications, with GLP-1 agonists being a prominent research area [1][2] - Novo Nordisk reported that a higher dose of Wegovy (semaglutide 7.2 mg) resulted in an average weight reduction of 21% for obesity patients, with one-third of participants losing 25% or more of their body weight [1][4] - The competitive landscape includes multiple companies, with Novo Nordisk leading in the number of obesity drug pipelines, followed by Eli Lilly and several domestic firms [1][6] Company Developments - Novo Nordisk's STEP UP trial demonstrated significant weight loss effects with the higher dose of semaglutide, maintaining safety profiles consistent with existing GLP-1 medications [2][4] - Eli Lilly announced positive results for its oral small molecule GLP-1 receptor agonist, Orforglipron, showing significant reductions in A1C levels and an average weight loss of 7.3 kg in the highest dose group [5] - Novo Nordisk plans to submit a label update for the higher dose of Wegovy in the EU by mid-2025, while Eli Lilly aims to submit Orforglipron for weight management approval by the end of this year [4][5] Industry Trends - The focus on innovative mechanisms for weight loss drugs includes long-acting, oral, multi-target, and muscle-preserving approaches, indicating a shift towards more effective treatment options [6][8] - The dual and triple-target GLP-1 agonists are gaining traction, with Eli Lilly's Retatrutide leading in global development, while several Chinese companies are advancing their products into clinical phases [7][8] - The market is seeing a growing number of combination therapies, with 13 dual-target and 9 multi-target combinations currently in development, totaling 88 related investigational drugs [7]

Core Viewpoint - The article discusses the potential of GLP-1 agonists, such as Wegovy and Ozempic, not only for weight loss but also for altering brain functions and reducing cravings for various substances, which could have significant implications for addiction treatment [2][3]. Group 1: Impact on Cravings and Addictions - Users of Wegovy report reduced cravings not only for food but also for alcohol, cigarettes, shopping, and nail-biting, suggesting a broader impact on addictive behaviors [2]. - A study involving over 500,000 individuals with a history of opioid use disorder indicated that those taking Ozempic or similar GLP-1 drugs had a significantly lower likelihood of opioid overdose compared to those not using these medications [2]. Group 2: Mechanisms and Effects on Mental Health - GLP-1 agonists may reduce the motivation for food and addictive substances by targeting brain areas responsible for food reward signals, which is currently being tested for potential use in treating alcohol and drug addiction [3]. - Research shows that GLP-1 agonists are associated with lower rates of anxiety and depression, potentially due to weight loss and the reduction of "food noise," allowing individuals to enjoy other aspects of life [5]. - A trial involving 19 patients with severe depression or bipolar disorder indicated that liraglutide improved mood, attention, and cognitive function, regardless of weight loss [7]. Group 3: Ongoing Research and Side Effects - The mechanisms behind GLP-1's effects are still being studied, with researchers noting that understanding these mechanisms could help address significant health questions [8]. - Side effects of semaglutide include constipation, muscle wasting, and accelerated facial aging, which may arise from changes in fat tissue and stem cell growth [8]. - There is excitement about the potential broad applications of semaglutide, with ongoing discussions about its possible benefits for various conditions, including cancer and Alzheimer's disease, although more research is needed to validate these claims [10].