以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 《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。 在减重药物领域，司美格鲁肽无疑是近年来的"明星选手"。作为胰高血糖素样肽-1受体(GLP-1R)激动剂，它通过刺激胰岛素分泌、调节代谢和 抑制食欲，实现了显著的减重效果，掀起全球减重药物革命。 肠促胰岛素激素家族堪称人类对抗肥胖的宝库。除了GLP-1R，另一位家族成员葡萄糖依赖性促胰岛素多肽受体(GIPR)近年来也成为研究热 点。双靶点减重药物替尔泊肽正是同时激动GIPR和GLP-1R的代表作。 然而，科学家们在研究中发现了一个令人困惑的现象：GIPR这个靶点似乎"任性"得让人难以理解——无论是激活它还是抑制它，竟然都能达 到减重效果！虽然最终结果相似，但中间机制却一直是个谜。 肥胖世界ObesityWorld . 单核RNA测序结果更是令人惊讶：近30万个细胞的分析显示，GIPR拮抗和激动在大脑中诱发的转录反应几乎完全相反。在脑干背侧迷走神经 复合体中，GIPR拮抗剂引起的转录反应与GLP-1 ...

Investment Rating - The investment rating for the pharmaceutical and biotechnology industry is "Positive" (maintained) [1] Core Insights - Major multinational corporations (MNCs) such as Pfizer, Eli Lilly, and Novo Nordisk are actively expanding their long-acting pipelines and technology platforms, with Pfizer's acquisition of Metsera for approximately $9.2 billion being a significant move [4][14] - The report anticipates that long-acting new therapies will become a key competitive direction in the weight loss and diabetes treatment sectors, with increasing clinical data expected to highlight the value of these long-acting pipelines and technology platforms [14][30] Summary by Sections Long-Acting Revolution in Weight Loss - The long-acting revolution in the weight loss sector is being driven by MNCs, with Pfizer's acquisition of Metsera providing access to core assets like MET-097i and MET-233i, which are long-acting GLP-1 receptor agonists and amylin analogs [4][14] - The HALO platform from Metsera allows for significant extension of drug half-lives, with MET-097i and MET-233i having half-lives of approximately 15.8 days and 19 days, respectively [30][31] Key Technologies for Long-Acting Delivery - The report identifies several key technologies for achieving long-acting drug delivery, including: - **Antibody-Drug Conjugation**: A mature technology exemplified by Amgen's AMG133, which is in Phase III clinical trials [18] - **Fatty Acid End Modification**: Gaining attention following Pfizer's acquisition of Metsera, with platforms like MBX's dual fatty acid chain modification technology also in development [24][33] - **Subcutaneous Reservoir Controlled Release**: Widely applicable technology with strategic partnerships formed by Eli Lilly and Novo Nordisk [5][12] - **Peptide Stapling Technology**: Enhances the stability of short peptides, with companies like Zhongsheng Pharmaceutical and Tonghua Dongbao developing relevant products [6][17] Recommended Companies - The report recommends focusing on innovative drugs and their supply chains, particularly in the context of flu-related investment opportunities. Monthly and weekly recommended stocks include: - Monthly: 3SBio, Innovent Biologics, Baillie Gifford, Frontier Biotechnologies, Haofan Biologics, Aopumai, Shanghai Yizhong, WuXi Biologics, Zai Lab, and Fangsheng Pharmaceutical [7] - Weekly: Yuyuan Pharmaceutical, East China Pharmaceutical, Hotgen Biotech, Yaokang Biotech, Bid Pharmaceutical, Haoyuan Pharmaceutical, and Sunshine Novo [7]

Summary of Key Points from the Conference Call Industry Overview - The conference focused on advancements in the pharmaceutical industry, particularly in the development of weight loss and glucose-lowering medications, highlighted during the 2025 ADA conference [1][2]. Core Insights and Arguments - **CagriSema by Novo Nordisk**: This drug combines GLP-1 and Amylin receptor agonists, showing a weight reduction of 22.7% over 75 weeks, with a net effect of 20.4%. However, nausea was reported more frequently than with semaglutide alone [1][11]. - **AMG133**: This drug acts as a GLP-1 receptor agonist and GIP receptor antagonist. In a Phase II trial, the high-dose group (420 mg) achieved nearly 20% weight loss, with an adjusted effect of about 16% after accounting for IVG effects [1][13]. - **Bimagrumab**: When used in combination with semaglutide, it reduced muscle loss associated with semaglutide, leading to weight loss primarily from fat tissue. However, higher rates of diarrhea and muscle cramps were noted in the high-dose combination group [1][2]. - **Eli Lilly's Small Molecule GLP-1 Agonist**: In the Achieve One Phase III trial, the 36 mg dose resulted in nearly 8% weight loss, but higher doses did not show a clear dose-response relationship, with gastrointestinal issues being the main adverse effects [1][9][10]. - **Sema's Phase III Results**: The 2.4 mg group showed a significant weight loss of 15.4% over 48 weeks, outperforming semaglutide 2.4 mg and approaching the efficacy of tirzepatide [1][17]. Additional Important Content - **Emerging Drugs and Combination Therapies**: The conference highlighted several new drugs and combination therapies, emphasizing a multi-target strategy and the importance of preserving lean muscle mass during weight loss [5][6]. - **Adverse Effects**: Common gastrointestinal adverse effects were reported across various drugs, including nausea, vomiting, and diarrhea. The high-dose combination therapy groups experienced increased rates of these side effects, particularly nausea [8][14][23]. - **GRP5 Receptor Agonist VCTR20**: Developed by Wente and an international partner, this small molecule showed significant effects in weight loss and body composition in Phase II trials [4][6]. - **Future Directions**: The industry is moving towards multi-target therapies for comprehensive metabolic management, with promising results from three-target combinations showing better outcomes than dual-target therapies [24][25]. This summary encapsulates the key developments and insights from the conference, providing a comprehensive overview of the current landscape in weight loss and glucose-lowering drug development.