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 a perplexing ability to facilitate weight loss through both activation and inhibition, with distinct mechanisms involved [5][11]. - Recent studies reveal that GIPR agonists primarily act on GABAergic neurons, while antagonists rely on GLP-1R signaling, indicating different neuronal pathways activated in the central nervous system [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, has shown promising results in reducing appetite and promoting weight loss in animal models [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 tailored therapeutic strategies in obesity management [11].

整理 | GLP1减重宝典内容团队 近期，司美格鲁肽因显著的减重效果备受关注，但随之而来的"跟风式用药"现象却令人担忧。 一些人将药物当作"应急瘦身针"，不规律注射甚 至自行停药，结果不仅体重反弹，不良反应也明显增多。 医学界纷纷呼吁：肥胖是一种慢性病，减重药物的使用必须严格遵循长期管理方案， 盲目追求短期效果往往会适得其反。 还有一些人达到平台期后，继续用同一剂量的司美格鲁肽大多只能维持原体重或逐渐失效，从而停止用药。这些做法都是不对的。下面就来分析 下理由。 ▍"打一针瘦五斤"？不可药物滥用 在朋友眼中，身高158cm、体重110斤的许女士并不胖，可她却对减肥有着强烈的渴望。她打完第一针司美格鲁肽后的第一周，体重就降到了106 斤，她满心期待能回到体重不过百的状态。 然而，中国医学科学院内分泌科的专家指出，司美格鲁肽主要是通过调节食欲、延缓胃排空来发挥减重作用的，只有维持稳定的血药浓度，才能 达到理想的减重效果。如果随意注射、中断用药，就会打破身体的代谢节奏，不仅会影响药物的疗效，还可能加重胃肠道的不良反应，甚至有可 能诱发胰腺炎等严重风险。 北京协和医院肥胖门诊的医生也强调，这类药物并非短期就能解决问题 ...

Core Viewpoint - The article discusses the approval and clinical development of RAY1225, a GLP-1 receptor agonist developed by Guangdong Zhongsheng Ruichuang Biotechnology Co., Ltd., highlighting its potential in treating obesity and related complications, particularly obstructive sleep apnea [4][8]. Group 1: Product Approval and Clinical Trials - RAY1225 has received approval for a new clinical trial aimed at treating obesity combined with obstructive sleep apnea, marking it as one of the few GLP-1 candidates in this area [4]. - The drug has previously been approved for three indications: obesity, type 2 diabetes, and metabolic dysfunction-related fatty liver disease, covering key areas such as weight loss and blood sugar control [4]. - Currently, RAY1225 is advancing three Phase III clinical trials, including one focused on weight management in overweight and obese populations and two studies for type 2 diabetes treatment [7]. Group 2: Mechanism and Advantages - RAY1225 is characterized by its dual activation of GLP-1 and GIP receptors, promoting insulin secretion and suppressing glucagon release in a glucose-dependent manner, which aids in blood sugar control [5]. - The drug's pharmacokinetic properties allow for a longer exposure time and stable blood concentration, enabling a biweekly injection schedule, which is crucial for improving patient adherence [7]. Group 3: Commercialization and Market Potential - In January 2026, Zhongsheng Ruichuang entered a partnership with Qilu Pharmaceutical for the production and commercialization of RAY1225 in China, with a total transaction value of 1 billion yuan, indicating strong recognition of the product's clinical value and market potential [8]. - The expansion of RAY1225's indications, particularly into high comorbidity scenarios like obesity with obstructive sleep apnea, reflects a broader trend in the domestic GLP-1 development landscape towards addressing obesity-related complications [8].

Core Viewpoint - Novo Nordisk's oral GLP-1 weight loss drug, Wegovy, has exceeded market expectations with rapid prescription growth, outperforming its injectable version and competitors in the same category [4][6]. Group 1: Market Performance - In just two weeks post-launch, oral Wegovy achieved approximately 18,400 prescriptions, with some estimates nearing 20,000, compared to 1,600 for the injectable version and 7,300 for Eli Lilly's Zepbound during the same period [4]. - The strong performance of oral Wegovy is crucial for Novo Nordisk to regain its footing in the weight loss market, which has been challenged by Eli Lilly's competitive advantages [6]. Group 2: Product Attributes - Oral Wegovy received FDA approval in December 2025 as the first oral GLP-1 drug for obesity treatment, with a maximum daily dose of 25 mg and an indication for reducing cardiovascular risk, broadening its applicability [6]. - The pricing strategy for oral Wegovy is set at $149 per month for cash-paying patients, with a minimum of $25 for those with commercial insurance through the company's discount program, which is seen as a key factor for early adoption [6]. Group 3: Industry Implications - The rapid uptake of oral Wegovy signals strong market demand for oral GLP-1 weight loss drugs, potentially benefiting Eli Lilly's upcoming oral product, orforglipron [7]. - Analysts note that the competitive landscape is shifting from efficacy comparisons to factors like administration method, affordability, and long-term adherence, indicating a new phase in the weight loss drug market [8].

Core Viewpoint - The article emphasizes the importance of hydration for individuals using GLP-1 medications for weight loss, highlighting that adequate water intake can enhance the efficacy of the drugs and mitigate side effects [5][7][8]. Group 1: Importance of Hydration - Water constitutes about 20% of daily total water intake from food, and using GLP-1 medications may lead to reduced food intake and potential dehydration risks [5] - Proper hydration is crucial for digestion and drug metabolism, ensuring sufficient digestive fluids are available to aid in food breakdown and nutrient absorption [7] - Insufficient water intake can lead to constipation and bloating, which may hinder weight loss efforts [7] Group 2: Symptoms of Dehydration - Users of GLP-1 medications may experience mild dehydration, leading to symptoms such as headaches, muscle cramps, nausea, constipation, fatigue, and dizziness [8] - Dehydration can exacerbate common gastrointestinal side effects of GLP-1, such as nausea and constipation, making hydration particularly important for those experiencing vomiting or diarrhea [8] Group 3: Detoxification and Fat Metabolism - Water aids in the elimination of toxins released from fat cells during weight loss, preventing their accumulation and ensuring effective metabolism [9] - Adequate hydration is necessary for the body to metabolize fat efficiently, as insufficient water can slow down weight loss progress [10] Group 4: Energy Levels and Exercise Performance - Fatigue is a common side effect of dehydration and weight loss medications; drinking water can help restore energy levels [12] - Hydration is essential for muscle function, endurance, and recovery, especially when exercise is part of a weight loss plan [12] Group 5: Hydration Guidelines - There are no specific guidelines for water intake for individuals using GLP-1 medications, but general recommendations suggest women should consume about 91 ounces and men about 125 ounces of water daily [13] - Individual hydration needs may vary based on factors such as body size, other medications, outdoor temperature, and physical activity [13] Group 6: Monitoring Hydration - A simple method to check hydration status is by observing urine color; light yellow indicates adequate hydration, while dark yellow suggests a need for increased intake [14] - Keeping track of fluid intake and ensuring regular hydration throughout the day can help meet daily liquid goals [14]

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 such as nausea [7][12][14]. Group 1: Peptide Hormones and Their Role - Peptide hormones play a crucial role in regulating energy balance and appetite, making them ideal targets for obesity treatment [6]. - Over the past 40 years, scientists have identified 12 peptide substances involved in appetite regulation, but challenges remain in their discovery and functional characterization due to low abundance and difficulty in distinguishing active fragments from degradation products [6][9]. Group 2: Discovery of BRP - A significant study published by Stanford University utilized artificial intelligence to identify BRP, which effectively reduces food intake in mouse and pig models without causing nausea [7][12]. - BRP was found to activate the FOS protein in the central nervous system, independent of leptin, GLP-1 receptor, and melanocortin 4 receptor signaling pathways [7][12]. Group 3: Mechanism of Action - BRP's mechanism involves the activation of the CREB-FOS signaling pathway, which is crucial for its appetite-suppressing effects [20][22]. - The peptide was shown to induce significant phosphorylation of CREB and increase intracellular cAMP levels, indicating its action through Gαs-coupled GPCRs [20][22]. Group 4: Efficacy and Safety - In studies, BRP demonstrated a dose-dependent effect on food intake, with a 5 mg/kg dose significantly reducing consumption and a 20 mg/kg dose nearly completely suppressing it [12][13]. - Importantly, BRP did not affect animal activity, water intake, or induce aversive reactions, highlighting its potential as a safe weight-loss agent [13][14]. Group 5: Comparative Effectiveness - In pig models, BRP reduced food intake by 50% within one hour, showing effects comparable to GLP-1 receptor agonists like liraglutide [15]. - In obese mouse models, BRP treatment led to a significant reduction in body weight and fat mass without muscle loss, indicating its effectiveness in targeting fat reduction [17]. Group 6: Future Implications - The innovative methods used to identify BRP and its demonstrated efficacy suggest it could be a valuable therapeutic option for obesity treatment, potentially offering a new avenue for weight management without the side effects associated with current treatments [22].

Core Viewpoint - The global GLP-1 market is shifting, with multinational pharmaceutical companies increasingly focusing on Chinese biopharmaceutical assets, a trend expected to peak in 2025 and be confirmed in early 2026 [5] Group 1: Market Dynamics - The competition in the weight loss and metabolic disease market is evolving from single product competition to a comprehensive contest involving multiple mechanisms, indications, and long-term medication [5] - Multinational pharmaceutical companies are experiencing anxiety regarding pipeline breadth and technological reserves, with China emerging as a key source for supplementing GLP-1 pipelines [5] - Over the past decade, the role of Chinese innovative drug companies has shifted from introducing overseas technology to exporting self-developed assets [5] Group 2: Asset Development - Chinese companies have accumulated a number of candidates in the GLP-1 field, particularly in dual-target, triple-target, and oral formulations, with several in Phase II and III [5] - These assets are characterized by preliminary validation of scientific pathways and identifiable clinical risks, making them valuable for multinational companies to quickly fill their pipelines through licensing or acquisition [5] Group 3: Transaction Highlights - Novo Nordisk made a significant move by securing rights to a triple-target agonist, UBT251, with a payment structure of $200 million upfront and up to $1.8 billion in milestone payments, reflecting a strategic choice to rebuild its next-generation weight loss product lineup [7] - Regeneron entered a licensing agreement with Hansoh Pharma worth over $2 billion for a GLP-1/GIP dual-target agonist in Phase III, aiming to strengthen its position in the metabolic disease field [7] - Pfizer, after terminating two late-stage oral GLP-1 candidates due to safety issues, acquired Metsera for nearly $10 billion and entered a licensing agreement with YaoPharma for an early-stage oral GLP-1 candidate, demonstrating a cautious approach to re-entering the oral weight loss drug market [7] Group 4: Strategic Implications - These transactions signal that multinational pharmaceutical companies are preparing for the second phase of competition in the GLP-1 market, focusing on efficacy limits, medication convenience, long-term safety, and combination therapy potential [8] - The shift indicates a structural adjustment in the global pharmaceutical industry, with China transitioning from merely a clinical trial and production base to a significant technology supplier in key therapeutic areas [8]

Core Insights - The article discusses the impending patent expiration of GLP-1 drugs, particularly semaglutide, in March 2026, which is expected to trigger a significant shift in the Indian market for these weight loss and diabetes medications [4][6] - Indian pharmaceutical companies are preparing to enter the GLP-1 market aggressively, with several firms already obtaining regulatory approvals to sell semaglutide formulations, indicating a pre-launch state [6][7] - The market for GLP-1 drugs in India has seen explosive growth, with the segment's size increasing from approximately 1.86 billion INR in November 2022 to over 10 billion INR by November 2025, reflecting a more than fivefold increase in just three years [6] Industry Dynamics - The Indian GLP-1 market is characterized by a competitive landscape where original drug manufacturers, like Eli Lilly and Novo Nordisk, are actively trying to maintain their market share through price reductions and product line expansions [7] - The outcome of ongoing legal proceedings regarding semaglutide's patent will significantly influence the market dynamics, with a ruling expected before the patent expiration [4][7] - The demand for GLP-1 drugs in India is anticipated to surge once price barriers are lowered, as the country has one of the largest diabetic populations globally, coupled with rising obesity rates [6]

Core Viewpoint - Tirzepatide is emerging as a leading candidate for treating overweight and obesity due to its significant weight loss effects and improvements in various metabolic parameters [5][7][8]. Group 1: Clinical Efficacy and Market Demand - In the SURMOUNT-5 clinical study, Tirzepatide demonstrated an average weight loss of 20.2% over 72 weeks in overweight adults with related comorbidities, significantly surpassing Semaglutide's 13.7% [8]. - Tirzepatide received approval for obesity treatment in November 2023 and for moderate to severe obstructive sleep apnea in December 2024, marking it as the first drug approved for this condition [8]. Group 2: Mechanism of Action - Tirzepatide activates GIP/GLP-1 receptors, promoting insulin secretion, inhibiting glucagon release, delaying gastric emptying, and suppressing appetite, which collectively aid in weight management and blood sugar control [9]. Group 3: Indications for Use - Tirzepatide is indicated for type 2 diabetes patients, particularly those with poor blood sugar control despite other treatments and those needing weight loss [10]. - It is also indicated for obesity management in adults with a BMI of ≥28 kg/m² or ≥24 kg/m² with at least one weight-related comorbidity [11]. Group 4: Contraindications and Cautions - Tirzepatide is not suitable for type 1 diabetes patients, those with acute diabetic ketoacidosis, severe gastrointestinal diseases, or a history of medullary thyroid carcinoma [12][13][14].

Core Viewpoint - The article discusses the increasing interest and cautious use of GLP-1 drugs among the elderly population for weight management and diabetes treatment, highlighting both potential benefits and necessary precautions [4][7][11]. Group 1: GLP-1 Drugs in Elderly Population - GLP-1 drugs have gained popularity among patients aged 65 and older, with many seeking these medications for weight management [4]. - The CDC reports that nearly 40% of individuals aged 60 and above are classified as obese, which significantly impacts their health and quality of life [4]. - Experts emphasize the importance of careful evaluation of elderly patients' overall health before prescribing GLP-1 drugs, particularly for those with frailty or cognitive impairments [7][11]. Group 2: Broader Implications of GLP-1 Drugs - Recent studies suggest that GLP-1 drugs may have effects beyond glucose control and weight loss, potentially influencing cardiovascular diseases, addiction behaviors, certain cancers, and cognitive function [5][9]. - In oncology, some studies indicate that patients using GLP-1 receptor agonists have lower all-cause mortality rates compared to other diabetes treatments, although the causal relationship remains unclear [10]. - The mechanism of GLP-1 receptor agonists involves mimicking natural hormones to slow gastric emptying and signal satiety to the brain, raising interest in their broader health impacts [7]. Group 3: Clinical Considerations and Future Research - Experts stress the need for a cautious approach when prescribing GLP-1 drugs to elderly patients, considering the potential for adverse effects and the complexity of their medication regimens [10][11]. - There is a growing recognition of the need for more representative clinical trial data for older adults, as current studies show that older patients may experience higher rates of discontinuation due to gastrointestinal side effects [11]. - The article concludes that with careful assessment and monitoring, GLP-1 drugs could provide significant benefits for some elderly patients, particularly when combined with lifestyle interventions [11].