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 . 核心发现： 1. 全球首次证实：GLP- 1 /GIP双受体激动剂Tir z e pa ti de能有效减少2型糖尿病患者肌肉脂肪沉积，同时保持肌肉量合理变化 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。 2. 5 2周治疗数据显示：患者体重显著降低同时，肌肉脂肪浸润程度明显改善，肌肉量变化与体重下降呈科学匹配 3. 创新研究方法：结合UK Bi oba nk近3000例真实世界数据，为临床结果提供精准参照系 研究价值与发表背景 这项具有里程碑意义的研究源自SURPASS- 3临床试验的MRI亚组分析，最新发表于《柳叶刀·糖尿病与内分泌学》2025年6月刊。研究 团队采用高精度MRI技术，系统对比了Tir z e pa ti de与德谷胰岛素治疗5 2周后，2型糖尿病患者大腿肌肉体积、脂肪浸润程度及标准化Z 分数的动态变化。 研究突破性地引入英国生物库大规模人群数据，首次建立了糖尿病药物治疗与肌肉健康变化的科学评价体系。这不仅为Tir z e p a ti de的 临床优势提供了影像学证 ...

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。 核心发现： 1. 全球首次证实：GLP- 1 /GIP双受体激动剂Tir z e pa ti de能有效减少2型糖尿病患者肌肉脂肪沉积，同时保持肌肉量合理变化 2. 5 2周治疗数据显示：患者体重显著降低同时，肌肉脂肪浸润程度明显改善，肌肉量变化与体重下降呈科学匹配 3. 创新研究方法：结合UK Bi oba nk近3000例真实世界数据，为临床结果提供精准参照系 研究价值与发表背景 这项具有里程碑意义的研究源自SURPASS- 3临床试验的MRI亚组分析，最新发表于《柳叶刀·糖尿病与内分泌学》2025年6月刊。研究 团队采用高精度MRI技术，系统对比了Tir z e pa ti de与德谷胰岛素治疗5 2周后，2型糖尿病患者大腿肌肉体积、脂肪浸润程度及标准化Z 分数的动态变化。 研究突破性地引入英国生物库大规模人群数据，首次建立了糖尿病药物治疗与肌肉健康变化的科学评价体系。这不仅为Tir z e p a ti de的 临床优势提供了影像学证 ...

Core Viewpoint - GIP (Gastric Inhibitory Polypeptide) plays a crucial role in insulin secretion and glucose metabolism, especially in the context of type 2 diabetes (T2D), where its function is often impaired. Recent studies highlight the significance of GIP in enhancing the efficacy of diabetes treatments, particularly through the development of dual receptor agonists like Tirzepatide [2][4]. Group 1: GIP and Its Role in Diabetes - GIP is secreted by intestinal K cells and, along with GLP-1, is classified as an incretin hormone that stimulates insulin secretion, helping to clear approximately 80% of glucose absorbed from food. In T2D patients, the function of incretins is nearly lost, making the restoration of this function vital for treatment [2]. - After oral glucose intake, GIP is responsible for about 44% of insulin secretion, while GLP-1 accounts for only 22% [2]. Group 2: Tirzepatide Overview - Tirzepatide is a modified peptide based on the GIP sequence and is recognized as a leading GLP-1/GIP dual receptor agonist. It has a half-life of 5 days, allowing for weekly administration [4]. - Clinical trials indicate that Tirzepatide outperforms GLP-1 single receptor agonists, such as Semaglutide, in controlling blood sugar and reducing weight [4]. Group 3: Efficacy of Tirzepatide - In the SURMOUNT-1 study, patients treated with Tirzepatide (5mg, 10mg, and 15mg) experienced significant weight loss of 15.4%, 19.9%, and 22.9% respectively, compared to a mere 2.1% in the placebo group over 176 weeks. Additionally, Tirzepatide reduced the risk of diabetes progression by 88% [6]. - The SURMOUNT-2 study confirmed that higher doses of Tirzepatide led to an average weight loss of 15.7% (15.6kg) in obese patients with T2D over 72 weeks, with 81.6% and 86.4% of patients in the 10mg and 15mg groups losing over 5% of their body weight, respectively [8]. - The SURMOUNT-3 trial showed a weight reduction of up to 26.6% after 12 weeks of lifestyle intervention and 72 weeks of Tirzepatide treatment [10]. - In the SURMOUNT-4 trial, participants lost an average of 26.0% of their body weight over 88 weeks, with a 21.1% reduction during the initial 36 weeks [11]. Group 4: Side Effects and Tolerability - Approximately 80% of Tirzepatide users report at least one side effect, primarily nausea, diarrhea, constipation, or vomiting, similar to those experienced with Semaglutide. Notably, 33% of patients on the highest dose of Tirzepatide reported nausea, compared to 44% for Semaglutide [12]. - Tirzepatide may have a lower frequency and milder symptoms of side effects compared to Semaglutide due to its dual action mechanism, which can mitigate some of the central nervous system-related side effects associated with GLP-1 [14].

Core Viewpoint - The article discusses the development and clinical research of HRS9531, a GLP-1/GIP dual receptor agonist, highlighting its potential in treating obesity and type 2 diabetes mellitus (T2DM) as global rates of these conditions rise [2]. Group 1: Research Findings - Research 1: HRS9531 injection showed a significant average weight loss of 22.8% in the treatment group compared to 1.7% in the placebo group after 36 weeks, with a difference of 21.1% (P<0.0001) [6]. - Research 2: In a 52-week study, HRS9531 maintained an average weight loss of up to 18.0% at week 32, while the placebo group experienced a weight gain of 0.74% [11]. - Research 3: The oral version of HRS9531 demonstrated good tolerability and a weight loss of 3.8 kg in the 10 mg group after 28 days, compared to 1.6 kg in the placebo group [17]. Group 2: Safety and Tolerability - In the first study, the adverse event rate was 91.8% for the HRS9531 group, primarily involving mild gastrointestinal issues, with no patients discontinuing treatment [7]. - The second study reported adverse event rates between 75.5% to 91.8% across different dosage groups, with no new safety risks identified [12]. - The oral formulation showed a total adverse event rate of 62.5% in the single-dose phase and 84.4% in the multiple-dose phase, with no severe adverse events reported [17]. Group 3: Future Outlook - HRS9531 is positioned as a leading candidate in the clinical development of GLP-1/GIP dual receptor agonists in China, with significant potential for managing obesity and T2DM [19]. - The dosing strategy indicates that switching to a bi-weekly administration after achieving initial weight management goals can maintain efficacy and improve long-term adherence [20]. - The development of the oral formulation fills a gap in the domestic market for GLP-1/GIP agents, supporting its broader application in metabolic disease treatment [20].

Core Viewpoint - Semaglutide, developed by Novo Nordisk, has significantly impacted the weight loss market with over $7.8 billion in global sales in Q1 this year, approved for treating type 2 diabetes and obesity [2] - Tirzepatide, developed by Eli Lilly, is rapidly gaining ground, showing superior weight loss results compared to Semaglutide in recent studies [4][5] Group 1: Clinical Trial Results - In the SURMOUNT-5 trial, Tirzepatide led to an average weight loss of 20.2% (approximately 22.8 kg) over 72 weeks, with 31.6% of participants losing 25% or more of their body weight [5] - The REDEFINE 1 trial showed that the combination of Cagrilintide and Semaglutide (CagriSema) resulted in an average weight loss of 20.4% (approximately 26.6 kg) over 68 weeks, outperforming both Semaglutide and Cagrilintide alone [8] - In the REDEFINE 2 trial, CagriSema achieved an average weight loss of 13.7% in type 2 diabetes patients, significantly higher than the 3.4% in the placebo group [10][13] Group 2: Safety and Side Effects - CagriSema treatment was associated with a higher incidence of gastrointestinal adverse events (79.6%) compared to the placebo group (39.9%), though most symptoms were mild to moderate [8][13] - In the REDEFINE 2 trial, 72.5% of CagriSema participants reported gastrointestinal side effects, again higher than the 34.4% in the placebo group [13] Group 3: Market Outlook - The combination of Semaglutide and Cagrilintide shows potential to become a significant player in the obesity treatment market, alongside Semaglutide and Tirzepatide [14] - The results from recent clinical trials suggest that CagriSema may redefine the competitive landscape of weight loss medications, particularly in both diabetic and non-diabetic populations [14]