复旦大学附属中山医院内分泌科李小英主任、恒瑞医药霍仕文副总裁分别代表研究者和研发企业致辞。 霍仕文副总裁介绍了恒瑞医药在减重领域的产品布局情况以及HRS9531的开发进展。复旦大学附属中山 医院内分泌科赵琳教授向与会嘉宾及媒体详细介绍了HRS9531注射液Ⅲ期临床结果。 2025年11月19-22日，中华医学会糖尿病学分会第二十七次学术会议在西安顺利召开。会议期间，我国 首个自主研发的GLP-1/GIP双受体激动剂HRS9531注射液在中国超重或肥胖成人中的Ⅲ期临床试验 （GEMINI-1研究）结果媒体发布活动同步召开。 陈虹总监表示，恒瑞医药已在中国递交HRS9531用于长期体重管理的新药上市申请并获受理，在不久的 将来有望惠及广大超重患者。围绕HRS9531注射液目前还有一系列临床研究正在同步开展。其布局的适 应症涵盖阻塞性睡眠呼吸暂停、心力衰竭、骨关节炎、多囊卵巢综合征等多种与体重密切相关的疾病， 未来有望为更广泛的患者群体提供治疗选择，提升整体临床获益。 ...

Core Insights - The results of the phase III clinical trial (GEMINI-1 study) for HRS9531, a GLP-1/GIP dual receptor agonist developed by HengRui Medicine, were presented at the 2025 American Obesity Week conference, indicating promising weight loss effects and safety in overweight or obese adults in China [1][3] Group 1: Product Development - HRS9531 is designed for the treatment of overweight, obesity, related comorbidities, and type 2 diabetes [3] - The clinical trials for HRS9531 have involved over 2,000 participants in China [3] Group 2: Clinical Trial Results - The study demonstrated that HRS9531 has beneficial effects not only on weight loss but also in the cardiovascular metabolic domain [1]

Core Viewpoint - HengRui Medicine and Kailera Therapeutics have announced significant results from the Phase III clinical trial of the GLP-1/GIP dual receptor agonist HRS9531, demonstrating substantial weight loss compared to the placebo group [1] Group 1: Clinical Trial Results - After 48 weeks of treatment, the average weight loss percentage in the HRS9531 groups was significantly better than that of the placebo group, with the 6 mg group achieving an average weight loss of 19.2% [1] - Previous Phase II clinical trial results indicated that the 8 mg group had an average weight loss of 23.6% [1] Group 2: Future Plans - HengRui Medicine has submitted a new drug application, while Kailera plans to initiate global Phase III clinical trials by the end of the year [1]

Core Viewpoint - The article discusses the advancements and efficacy of Tirzepatide, a dual GLP-1/GIP receptor agonist, in treating obesity and type 2 diabetes, highlighting its superior weight loss results compared to traditional GLP-1 receptor agonists like Semaglutide [7][10][12]. Group 1: Mechanism and Efficacy - GIP plays a crucial role in insulin secretion, accounting for approximately 44% of insulin release after oral glucose intake, while GLP-1 contributes only 22% [5]. - Tirzepatide, modified from GIP, has a half-life of 5 days, allowing for weekly administration, and shows better efficacy in blood sugar control and weight loss compared to GLP-1 receptor agonists [7][8]. - Clinical trials indicate that Tirzepatide significantly reduces body weight in patients with obesity or prediabetes, with weight loss percentages of 15.4% (5mg), 19.9% (10mg), and 22.9% (15mg) compared to a mere 2.1% in the placebo group [10]. Group 2: Clinical Trials and Results - The SURMOUNT-2 study demonstrated that higher doses of Tirzepatide led to an average weight loss of 15.7% (15.6kg) in type 2 diabetes patients over 72 weeks, with 81.6% of patients in the 10mg group losing over 5% of their body weight [12]. - 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 [14]. - In the SURMOUNT-5 trial, patients treated with Tirzepatide lost an average of 22.8kg, outperforming the active control group by 47% in weight loss [14]. Group 3: Safety and Side Effects - Approximately 80% of Tirzepatide users reported at least one side effect, primarily gastrointestinal issues such as nausea and diarrhea, similar to those experienced with Semaglutide [15]. - The incidence of nausea was reported at 33% for the highest dose of Tirzepatide, compared to 44% for Semaglutide, indicating a potentially lower side effect profile for Tirzepatide [15][17]. - GIP's role in appetite suppression may help mitigate some of the adverse effects associated with GLP-1 receptor activation, enhancing patient compliance and treatment efficacy [19].

Core Findings - The study confirms that the GLP-1/GIP dual receptor agonist Tirzepatide effectively reduces muscle fat deposition in type 2 diabetes patients while maintaining reasonable muscle mass changes [4][5] - After 52 weeks of treatment, patients showed significant weight loss and improved muscle fat infiltration, with muscle mass changes scientifically aligned with weight loss [4][5] - The research utilized data from the UK Biobank, involving nearly 3,000 real-world cases, providing a precise reference for clinical outcomes [4] Research Background - This milestone study originated from the MRI subgroup analysis of the SURPASS-3 clinical trial and was published in The Lancet Diabetes & Endocrinology in June 2025 [5] - The research team employed high-precision MRI technology to systematically compare the effects of Tirzepatide and insulin degludec on muscle volume and fat infiltration in type 2 diabetes patients [5][7] Clinical Significance - Weight management is a core strategy in type 2 diabetes treatment, with over 10% weight loss potentially leading to disease remission and cardiovascular benefits [7] - Traditional weight loss methods often result in muscle loss, increasing the risk of sarcopenia in elderly patients [7] - Tirzepatide, as the first GIP/GLP-1 dual receptor agonist, has demonstrated superior weight loss and fat regulation effects, with this study providing authoritative data on its impact on muscle composition [7][8] Research Methodology - The study employed an international multicenter, randomized controlled trial design, including strictly defined type 2 diabetes patients [8] - Participants were divided into four groups: Tirzepatide 5mg/10mg/15mg weekly injection groups and a daily injection control group of insulin degludec [8] Research Highlights - Precise imaging assessments were conducted at baseline and after 52 weeks using MRI to quantify thigh muscle fat infiltration and muscle volume [9] - The introduction of UK Biobank data established a muscle-weight change model, enhancing the generalizability of the results [9] - Key findings indicated that weight loss does not equate to muscle loss, showcasing Tirzepatide's unique advantages [9][10] Clinical Breakthrough - The study innovatively used MRI technology to assess the effects of Tirzepatide on muscle composition, revealing that significant weight loss (average 10.1%) coincided with reduced muscle fat infiltration [13] - The findings challenge the traditional belief that weight loss necessarily leads to muscle loss, providing a new perspective for diabetes management [13] Multiple Clinical Benefits - Tirzepatide demonstrated a unique "fat loss with muscle preservation" advantage, significantly reducing muscle fat infiltration by 0.36 percentage points [15] - The muscle volume reduction of 0.64 liters was proportionate to weight loss, outperforming muscle loss associated with simple dieting [15] - The study supports the notion of comprehensive metabolic improvement through multi-target collaboration, including reductions in liver fat and visceral fat [15] Clinical Decision-Making - The research fills a gap in muscle safety data for new hypoglycemic agents, offering critical decision-making references for clinicians [15] - For patients needing enhanced weight management, especially those with obesity and fatty liver, Tirzepatide is recommended as a priority choice [15] - The study provides objective imaging assessment standards for developing personalized treatment plans [15] Research Limitations and Future Directions - The study did not assess changes in muscle strength and daily activity capabilities [15] - There was a lack of strict control over lifestyle factors such as diet and exercise [15] - Long-term efficacy and safety beyond one year require further validation [15] - The research sets the stage for future exploration of drug-exercise combined interventions and treatment strategies for special populations [15]

Core Findings - The study confirms that the GLP-1/GIP dual receptor agonist Tirzepatide effectively reduces muscle fat deposition in type 2 diabetes patients while maintaining reasonable muscle mass changes [4][5] - After 52 weeks of treatment, patients showed significant weight loss and improved muscle fat infiltration, with muscle mass changes scientifically aligned with weight loss [4][5] - The research utilized data from the UK Biobank, involving nearly 3,000 real-world cases, providing a precise reference for clinical outcomes [4] Research Background - This milestone study originated from the MRI subgroup analysis of the SURPASS-3 clinical trial and was published in The Lancet Diabetes & Endocrinology in June 2025 [5] - The research team employed high-precision MRI technology to systematically compare the effects of Tirzepatide and insulin degludec on muscle volume and fat infiltration in type 2 diabetes patients [5][7] Clinical Significance - Weight management is a core strategy in type 2 diabetes treatment, with over 10% weight loss potentially leading to disease remission and cardiovascular benefits [7] - Traditional weight loss methods often result in muscle loss, increasing the risk of sarcopenia in elderly patients [7] - Tirzepatide, as the first GIP/GLP-1 dual receptor agonist, has demonstrated superior weight loss and fat control effects, with this study providing authoritative data on its impact on muscle composition [7][8] Research Methodology - The study employed an international multicenter, randomized controlled trial design, including strictly defined type 2 diabetes patients [8] - Participants were divided into four groups: Tirzepatide 5mg/10mg/15mg weekly injection groups and a daily injection control group of insulin degludec [8] Research Highlights - Precise imaging assessments were conducted at baseline and after 52 weeks using MRI to quantify thigh muscle fat infiltration and muscle volume [9] - The introduction of UK Biobank data established a muscle-weight change model, enhancing the generalizability of the results [9] - Key findings indicated that weight loss does not equate to muscle loss, showcasing Tirzepatide's unique advantages [9][10] Clinical Breakthrough - The study innovatively used MRI technology to assess the dual benefits of weight loss and muscle quality optimization in diabetes treatment [13] - Tirzepatide achieved significant weight loss (average 10.1%) while effectively reducing muscle fat infiltration, with muscle mass decrease within physiological adaptation limits [13][15] Multiple Clinical Benefits - Tirzepatide demonstrated a unique "fat loss, muscle preservation" advantage, significantly lowering muscle fat infiltration by 0.36 percentage points [15] - The muscle volume decrease of 0.64 liters was proportionate to weight loss, outperforming muscle loss from simple dieting [15] - The study provides critical decision-making references for clinicians, especially for patients needing enhanced weight management [15] Limitations and Future Directions - The study did not assess changes in muscle strength and daily activity capabilities [15] - There was a lack of strict control over lifestyle factors such as diet and exercise [15] - Long-term efficacy and safety beyond one year require further validation [15] - The research lays the groundwork for future exploration of drug-exercise combined interventions and tailored treatment strategies for specific populations [15]

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]