预约演示
更新于：2025-04-19
Dulaglutide
度拉糖肽
更新于：2025-04-19
概要
基本信息
原研机构 |
非在研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2014-09-18), |
最高研发阶段(中国)批准上市 |
特殊审评优先审评 (中国) |
登录后查看时间轴
结构/序列
Sequence Code 51033
来源: *****
关联
135
项与 度拉糖肽 相关的临床试验NCT06851962
Single-blinded, Double-arm, Controlled, Randomized, Multicentre Clinical Trial to Evaluate the Impact of Pharmacogenetic-guided Treatment in Patients With Insufficiently Controlled Type 2 Diabetes
The goal of this clinical trial is to assess the efficacy of a pharmacogenetics-guided treatment, compared to standard optimized treatment, in patients with inadequately controlled type 2 diabetes. The main questions it aims to answer are:
* Is the disease better controlled when the treatment prescribed is based on the participant's pharmacogenetic profile?
* What medical problems do participants experience while taking the treatment?
Participants will:
* Take the treatment described according to the Summary of Product Characteristics (SmPC).
* Visit the clinic once every 12 weeks for checkups and tests.
* Keep a diary of their symptoms to inform the Investigator.
* Is the disease better controlled when the treatment prescribed is based on the participant's pharmacogenetic profile?
* What medical problems do participants experience while taking the treatment?
Participants will:
* Take the treatment described according to the Summary of Product Characteristics (SmPC).
* Visit the clinic once every 12 weeks for checkups and tests.
* Keep a diary of their symptoms to inform the Investigator.
开始日期2025-04-01 |
申办/合作机构- |
ChiCTR2500098958
Targeted GLP-1R PET imaging in the clinical application of endogenous hyperinsulinemia
开始日期2025-03-18 |
申办/合作机构- |
ACTRN12624001245583
SUBDUE-3: A Phase 0 study of SUB-urothelial DUrvalumab-Zirconium to investigate local and systemic distribution of Durvalumab when injected in the sub-urothelium of adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder cancer
开始日期2025-02-10 |
申办/合作机构- |
100 项与 度拉糖肽 相关的临床结果
登录后查看更多信息
100 项与 度拉糖肽 相关的转化医学
登录后查看更多信息
100 项与 度拉糖肽 相关的专利（医药）
登录后查看更多信息
1,467
项与 度拉糖肽 相关的文献（医药）2025-05-01·PHARMACOLOGY & THERAPEUTICS
GLP-1 receptor agonists, are we witnessing the emergence of a paradigm shift for neuro-cardio-metabolic disorders?
Review
作者: Arredouani, Abdelilah
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as groundbreaking therapeutic agents in managing a spectrum of metabolic disorders, demonstrating remarkable efficacy across multiple organ systems and disease states. These compounds are not only well-established in the treatment of type 2 diabetes (T2D) and obesity-conditions for which they have received widespread approval-but also exhibit promising potential in addressing cardiovascular disease (CVD) and Metabolic dysfunction-associated steatotic liver disease (MASLD). Recent investigations have begun to illuminate the utility of GLP-1RAs in the management of type 1 diabetes (T1D), as well as neurodegenerative disorders such as Alzheimer's and Parkinson's disease and various behavioral disorders. A plethora of clinical trials have consistently validated the capacity of GLP-1RAs to improve glycemic control, promote weight loss, and mitigate cardiovascular risk factors in individuals with T2D and obesity. While their application in T1D remains limited due to safety concerns-particularly regarding the risks of hypoglycemia and hyperglycemic ketoacidosis-emerging data suggest that GLP-1RAs may offer hepatoprotective benefits, potentially reducing liver fat content and decelerating the progression of MASLD. The neuroprotective attributes of GLP-1 RAs have garnered significant interest, with research indicating their potential to alleviate cognitive decline associated with neurodegenerative diseases. Furthermore, preliminary findings highlight the role of GLP-1 RAs in addressing behavioral disorders, emphasizing their extensive therapeutic promise. This comprehensive review synthesizes the current evidence supporting the diverse therapeutic applications of GLP-1RAs, positioning them as "magic drug" therapies for metabolic and neurological disorders. As ongoing research continues to explore innovative applications and combinations of GLP-1RAs, the landscape of disease management in metabolic and neurological contexts is poised for transformative advancements. This review will also critically assess safety considerations and underscore the need for personalized treatment strategies to optimize patient outcomes in these complex and often comorbid conditions.
2025-05-01·SLEEP MEDICINE
Efficacy and safety of GLP-1 receptor agonists in the management of obstructive sleep apnea in individuals without diabetes: A systematic review and meta-analysis of randomized, placebo-controlled trials
Review
作者: Hasan, Syed Shahzad ; Thiruchelvam, Kaeshaelya ; Ramachandram, Dinesh Sangarran ; Kow, Chia Siang
INTRODUCTION:
Obstructive sleep apnea (OSA) is a common sleep disorder that disrupts breathing during sleep. While continuous positive airway pressure therapy is the standard treatment, poor adherence has led to exploration of alternative treatments. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce body weight and may help manage OSA. This systematic review and meta-analysis evaluated the efficacy and safety of GLP-1 RAs in individuals with OSA and elevated body weight who are without diabetes.
METHODS:
A systematic search was conducted in September 2024 across multiple databases. Randomized controlled trials (RCTs) evaluating GLP-1 RAs for OSA in adults with a body mass index (BMI) ≥30 kg/m2 were included. The primary outcomes were changes in the apnea-hypopnea index (AHI) and overall adverse events. Meta-analyses were performed using a random-effects model.
RESULTS:
Three RCTs were included in the analysis. Pooled results showed that GLP-1 RA treatment significantly reduced AHI compared to placebo, with a weighted mean difference (WMD) of -16.6 events per hour (95 % confidence interval [CI]: -27.9 to -5.3). However, GLP-1 RAs were associated with a higher frequency of adverse events, with an odds ratio (OR) of 1.62 (95 % CI: 1.16 to 2.24) compared to placebo.
CONCLUSION:
GLP-1 RAs effectively reduce OSA severity, offering a promising alternative for individuals with OSA and elevated body weight. However, the increased risk of side effects must be considered. Further long-term studies are needed to confirm the sustained benefits and safety of GLP-1 RAs in OSA management.
2025-05-01·NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Protective effect of Dulaglutide, a GLP1 agonist, on acetic acid-induced ulcerative colitis in rats: involvement of GLP-1, TFF-3, and TGF-β/PI3K/NF-κB signaling pathway
Article
作者: Abdelmageed, Marwa E. ; Helal, Manar G ; Helal, Manar G. ; Mahdy, Raghda N. El ; Abu-Risha, Sally E ; Mahdy, Raghda N El ; Abu-Risha, Sally E. ; Abdelmageed, Marwa E ; Nader, Manar A ; Nader, Manar A.
Abstract:
A chronic inflammatory condition of the colon called ulcerative colitis (UC) is characterized by mucosal surface irritation that extends from the rectum to the near proximal colon portions. The rationale of this work was to conclude if dulaglutide (Dula) could protect rats from developing colitis caused by exposure to acetic acid (AA). Rats were randomly divided into seven groups (each with eight rats): Normal control, Dula control, AA (received 2 milliliters of 3% v/v AA through the rectum), Sulfasalazine (SLZ); given SLZ (100 mg/kg) orally from day 11 to day 21 then AA intrarectally on day 22 and Dula groups ( pretreated with 50, 100 or 150 μg/kg subcutaneous injection of Dula - once weekly for three weeks and AA on day 22 to induce ulcerative colitis, colon tissues and blood samples were taken on day 23. By generating colonic histological deviations such as inflammatory processes, goblet cell death, glandular hyperplasia, and mucosa ulcers, Dula dropped AA-induced colitis. Additionally, these modifications diminished blood lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon. In addition, Dula decreased the oxidative stress biomarker malondialdehyde (MDA) and increased the antioxidant enzymes (total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) concentrations). Dula also significantly reduced the expression of transforming growth factor-1 (TGF-β1), phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT) signaling pathway, and the inflammatory cytokines: nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interferon-γ (IFN-γ) in colonic cellular structures. In addition, Dula enforced the levels of glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3) that were crucial to intestinal mucosa regeneration and healing of wounds. By modulating TGF-β1 in conjunction with other inflammatory pathways like PI3K/AKT and NF-κB, regulating the oxidant/antioxidant balance, and improving the integrity of the intestinal barrier, Dula prevented AA-induced colitis in rats.
1,217
项与 度拉糖肽 相关的新闻（医药）2025-04-18
关注并星标CPHI制药在线从2025年起至2029年，多款生物制剂将陆续面临专利保护终止的节点，涵盖肿瘤、自身免疫、代谢紊乱及罕见病等多个高价值治疗领域（图1）。这些面临专利悬崖的重要药物不仅在全球药品销售榜上长期占据前列，也在各大跨国药企的收入结构中扮演核心角色。随着专利期的结束，生物类似药的进入将加速重塑市场竞争格局，为仿制药企打开数十亿美元级别的商业机会，同时也迫使原研药企加快布局生命周期管理、差异化竞争与市场准入策略的调整。专利悬崖不仅意味着法律地位的转变，更预示着一个新的竞争周期的开启。 图1. 2025-2029年部分生物制剂专利到期时间轴。2025年：HER2靶向格局或生变，自免仿制潜力渐显2025年将成为HER2阳性乳腺癌治疗领域的一个转折点。基因泰克的Perjeta（Pertuzumab，帕妥珠单抗，中国商品名：帕捷特）专利即将到期，这款与Herceptin联用的疗法是乳腺癌靶向治疗的重要基石。尽管生物类似药的开发在结构与疗效比对上仍有一定技术门槛，但已有多家公司布局相关管线，预示着HER2靶向治疗未来将走向价格优化与市场细分并行的格局。同样在2025年面临专利悬崖的GSK的Benlysta（belimumab，贝利尤单抗，中国商品名：倍力腾）是系统性红斑狼疮领域的首个生物制剂。其结构相对传统，开发难度较低，因此生物类似药的进入预计将更加迅速，有望打破目前该领域的高价垄断，扩大治疗的可及性。Blincyto（Blinatumomab，贝林妥欧单抗，中文商品名：贝利妥）为Amgen开发的双特异性抗体，用于治疗急性淋巴细胞白血病，其构建机制复杂、剂型特殊，对生物类似药开发提出更高挑战，仿制企业需具备扎实的双抗工艺平台。Elelyso（taliglucerase alfa）则针对戈谢病这一罕见病种，尽管市场规模有限，但在专利到期后，价格的适度下降可能带来治疗的边际人群扩大。2026年：自身免疫与软组织肿瘤治疗面临洗牌2026年，基因泰克的另一款 HER2阳性乳腺癌药物Kadcyla（ado-trastuzumab emtansin）专利即将到期。虽Kadcyla专利保护期将尽，但其作为 ADC模态的药物具有复杂的生产工艺和药代动力学特性，使得仿制门槛依然很高。其潜在生物类似药需在连接子稳定性、毒素释放效率等多个维度实现一致性，预计市场进入将较为谨慎。礼来的Lartruvo（Olaratumab，奥拉鲁单抗）尽管曾获FDA加速批准用于软组织肉瘤，但由于后期研究未达预期已退出市场，其专利到期更多具象征意义。而礼来另一款单抗药物Taltz（Ixekizumab，依奇珠单抗，中文商品名：拓咨）则是礼来在银屑病和银屑病关节炎领域的重要布局产品之一，其结构较为常规。随着IL-17通路药物竞争日趋激烈，Taltz的专利到期可能刺激同类产品价格联动式下调，也为生物类似药打开切入口。2027年：代谢病与罕见病治疗双线释放机会2027年，代谢性疾病治疗将成为焦点。礼来的Trulicity（Dulaglutide，度拉糖肽，中文商品名：度易达）为GLP-1受体激动剂类生物药，其在全球2型糖尿病管理中占据重要地位。尽管目前GLP-1药物以多肽新药（如semaglutide和tirzepatide）为主导，但生物类似药仍可能凭借医保放量和价格优势切入市场，特别是在发展中国家。需要指出的是，虽然度拉糖肽的名称似乎显示其分子模态为多肽，但根据FDA的标准，该药物属于蛋白质（氨基酸残基数量远大于40）。Repatha（Evolocumab，依洛尤单抗，中文商品名：瑞百安）则是降脂治疗领域的明星产品，靶向PCSK9，技术结构相对清晰，安进的原研市场或将迎来仿制挑战者。另一方面，罕见病药物如Myalept（metreleptin，中文商品名：美曲普汀）与Sylvant（siltuximab，司妥昔单抗，中文商品名：萨温珂）分别用于脂肪营养不良与Castleman病，尽管患者基数较小，但在定价上长期维持高位，仿制药若成功推出，将显著影响药企盈利结构。2028年：免疫肿瘤黄金时代走向价格重估2028年将是免疫肿瘤药物市场重新洗牌的关键时刻。默沙东的Keytruda（Pembrolizumab，帕博利珠单抗，中文商品名：可瑞达）与BMS的Opdivo（Nivolumab，纳武利尤单抗，中文商品名：欧狄沃）这两大令人高山仰止的肿瘤学产品均将步入专利到期周期，这两款超巨重磅炸弹PD-1免疫检查点抑制剂几乎主导了全球多个癌种的一线免疫治疗格局。尽管其结构相对标准，技术仿制障碍较低，但监管机构对生物类似药在免疫肿瘤领域的临床一致性要求极高，加之其适应症广泛，将使得生物类似药的开发必须精细划分适应症并分阶段获批，逐步蚕食市场份额。专利到期将加速PD-1药物在中低收入市场的普及，也可能促使原研药大幅调整定价策略，以留存市场份额。2029年：自身免疫与血液瘤市场再迎竞逐到2029年，更多大体量产品将面对专利悬崖 。强生的Darzalex（Daratumumab，达雷妥尤单抗，中文商品名 ：兆珂）作为CD38靶点的多发性骨髓瘤生物制剂，在全球范围内维持了稳定的市场扩张，是多发性骨髓瘤治疗的主力产品，随着其全球销售额突破百亿美元，专利到期后的市场争夺战料将激烈。其复杂糖基化模式以及Fc改造机制为仿制企业带来技术挑战，但在高价格驱动下，已有多家企业提前展开布局。Ocrevus（ocrelizumab，奥瑞珠单抗）则是罗氏在多发性硬化治疗中的核心资产，兼具高效与安全性，其结构仿制可行，但治疗窗要求精细，后续药物可能更注重使用便捷性与长期随访数据。诺华的Cosentyx（Secukinumab，司库奇尤单抗，中文名称：可善挺）与安进的Enbrel（Etanercept，依那西普）则均为成熟的自身免疫治疗药物，市场格局已经相对开放，生物类似药的渗透速度预计将更快，并可能引导IL通路及TNF通路药物价格进一步下探。而Enbrel在美国延长专利的多年争议也提醒市场，专利并非铁板一块，法律诉讼、授权模式与市场准入政策同样决定产品生命周期的真正终点。结语：从专利到市场，生物制剂的新周期已然开启随着2025–2029年间一系列重磅生物制剂的专利相继到期，原研药企需要重新审视生命周期管理策略，从新适应症拓展、给药方式创新，到自有生物类似药的内部布局，争取在失去专利保护后依然保有市场份额。而对于仿制药企业而言，技术平台成熟度、质量一致性、监管路径优化以及成本控制将是能否在新一轮“生物仿制潮”中脱颖而出的关键。更值得注意的是，随着医保体系对高值药物价格的持续挤压，以及新兴市场国家生物药仿制能力的提升，这一轮专利悬崖或许将不仅仅是一个商业接力的过程，更可能成为全球药物可及性提升与创新转化效率再平衡的重要契机。附表 2025-2029年面临专利悬崖的部分生物制剂END2025金笔奖征文即将截止，速来投稿！领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~
专利到期生物类似药抗体药物偶联物
2025-04-15
The U.S. Phase 2 trial aims to evaluate efficacy and safety of CX11 in doses up to 200 mg and different titration schemesThe trial is expected to enroll 250 patients to receive treatment over 36 weeks BERKELEY HEIGHTS, N.J., April 15, 2025 (GLOBE NEWSWIRE) -- Corxel Pharmaceuticals Limited (CORXEL), a clinical-stage biopharmaceutical company dedicated to developing innovative therapies for patients with cardiometabolic conditions around the world, today announced the clearance of an investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) for a U.S. Phase 2 trial of CX11, an investigational oral once-daily small molecule glucagon-like peptide-1 receptor agonist (GLP-1 RA). This randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of CX11 in patients with obesity and overweight conditions in the U.S., with enrollment expected to begin in the second quarter of 2025. CX11 (also known as “VCT220”), for which CORXEL acquired global ex-China rights from Suzhou Vincentage Pharma Co., Ltd (Vincentage) in December 2024, is a once-daily oral product candidate designed to offer a convenient alternative to injectable GLP-1 treatments. In a previous Phase 2 trial conducted by Vincentage in China, CX11 achieved competitive weight loss with favorable safety and tolerability. CORXEL’s U.S. Phase 2 trial targets to enroll 250 patients, including those with a BMI of ≥30 kg/m² or a BMI of ≥27 kg/m² with at least one weight-related comorbidity, to receive treatment over 36 weeks and to be further monitored over a 2-week follow-up period. Topline data from this trial is expected in the first half of 2026, and if positive, would pave the way for a global Phase 3 development. CORXEL’s partner Vincentage initiated a Phase 3 registrational obesity trial in China in November 2024. “We are excited to receive the Study May Proceed Letter from the FDA for the U.S. Phase 2 trial of CX11, a critical milestone in our mission to address the global burden of obesity and related cardiometabolic diseases,” said Bo Liang, Senior Vice President, Head of Clinical Development – Metabolic at CORXEL. “Currently approved GLP-1 therapies, while generally effective, often face obstacles such as weekly injections, titration difficulty, side effects and limited tolerability, maintaining weight loss and supply challenges for peptide-based therapies. With once-daily oral administration and promising clinical data, CX11 aims to address these issues, potentially offering a best-in-class convenient oral treatment solution for patients globally.” About CX11 CX11 is an investigational oral small molecule GLP-1 RA designed to address cardiometabolic conditions, with a primary focus on obese and overweight patients. With global ex-China rights acquired by CORXEL from Vincentage in December 2024, CX11 aims to overcome limitations of current injectable GLP-1 RAs by offering convenient, once-daily oral administration, weight reduction comparable to injectable GLP-1 RAs, favorable tolerability results, scalability and accessibility as a small molecule product candidate. Clinical data from Vincentage’s Phase 2 trial in China demonstrated competitive weight loss with a favorable safety and tolerability profile. CX11 is currently advancing into a U.S. Phase 2 trial by CORXEL and through a Phase 3 registrational trial in China conducted by Vincentage, positioning it as a potential best-in-class oral therapy for management of obesity and overweight conditions. About CORXEL’s U.S. Phase 2 Clinical Trial for CX11 CX11’s U.S. Phase 2 clinical trial is a randomized, double-blind, placebo-controlled trial, designed to assess the efficacy and safety profile of CX11 in individuals with obesity and overweight in the United States. The trial targets to enroll 250 patients, including those with a BMI of ≥30 kg/m² or a BMI of ≥27 kg/m² with at least one weight-related comorbidity. The trial will feature five treatment arms: four active treatment groups receiving 120 mg, 160 mg, 200 mg with fast titration, 200 mg with slow titration, of CX11, as well as a placebo group. Patients will receive treatment for 36 weeks and will be further monitored over a 2-week follow-up period. Topline data from this trial is expected to be released in the first half of 2026. About CORXEL CORXEL is a clinical-stage biopharmaceutical company dedicated to developing innovative therapies for patients with cardiometabolic conditions around the world. CORXEL is led by an experienced management team that has a strong track record of identifying, in-licensing and developing attractive clinical product candidates directed at validated targets with proven mechanisms of action (MoAs). CORXEL’s diverse portfolio of clinical-stage product candidates has the potential to redefine treatment standards and address key limitations of current therapies for multiple cardiometabolic indications. CORXEL is developing selective small molecule compounds across the cardiometabolic spectrum with the lead product candidate CX11, an oral GLP-1 receptor agonist (GLP-1 RA) for obese and overweight patients, JX10, a thrombolytic and anti-inflammatory agent for acute ischemic stroke (AIS) and JX09, a highly selective aldosterone synthase inhibitor (ASI) for hypertension. For further information about CORXEL, please visit www.corxelbio.com media@corxelbio.com
临床2期临床申请临床结果
2025-04-13
▎药明康德内容团队编辑胰高血糖素样肽-1受体激动剂（GLP-1RA）已被证实具有很大治疗潜力，包括降糖、减重，以及降低重大心血管不良事件风险和改善糖尿病患者肾脏预后。近期研究证据显示，GLP-1RA或有益于改善射血分数保留型心力衰竭（HFpEF）的患者的肾脏结局。部分大型临床试验亚组分析结果表明，GLP-1RA和钠-葡萄糖共转运蛋白2抑制剂（SGLT-2i）联合治疗，可减少糖尿病患者心力衰竭住院和肾脏疾病复合事件发生率。在此基础上加用非甾体盐皮质激素受体拮抗剂（MRA）非奈利酮，可能进一步强化心肾保护作用，相关研究结果显示，三联治疗预估可将心血管不良事件风险和慢性肾病进展风险分别降低35%和58%。但GLP-1RA+SGLT-2i+非奈利酮三联疗法的临床效益及适用人群仍需更多研究验证。GLP-1RA可降低糖尿病患者主要不良心血管事件发生风险和肾脏不良结局风险糖尿病是心血管疾病和慢性肾病最重要的危险因素之一。相比于无糖尿病患者，糖尿病患者罹患动脉粥样硬化性心血管疾病的风险高出2~4倍。慢性肾病是糖尿病的主要微血管并发症，会增加心血管疾病和死亡的风险。控制血糖水平有助于预防慢性肾病微血管并发症和心血管事件的发生。对于糖尿病合并心血管疾病或存在多种心血管和肾脏风险的患者，GLP-1RA是治疗可选择用药之一。LEADER试验纳入了2型糖尿病合并心血管高风险的患者9340例，研究人员将患者随机分配接受利拉鲁肽或安慰剂治疗。研究结果显示，平均随访3.8年，相比于安慰剂组，利拉鲁肽组患者的主要不良心血管事件（心血管死亡、非致死性心肌梗死或非致死性卒中的复合终点）减少了13%（HR=0.87）。SUSTAIN-6试验则显示，在2型糖尿病合并心血管高风险患者中，相比于安慰剂组，司美格鲁肽组（皮下注射，每周0.5 mg或1 mg）心血管不良事件风险降低26%（HR=0.74），卒中风险降低了26%。后续Harmony Outcomes、REWIND、AMPLITUDE-O等研究也证实了GLP-1RA在降低2型糖尿病合并心血管高风险患者心血管不良事件、心肌梗死和卒中风险方面的作用。GLP-1RA不仅具有降糖的作用，也具有减重效应。SELECT试验在肥胖[体重指数（BMI）≥27 kg/m2]合并心血管疾病但无糖尿病的患者中开展，探索使用GLP-1RA对于预防心血管事件发生的作用。研究结果显示，在平均3.3年的观察期内，相比于安慰剂，皮下注射司美格鲁肽可使患者体重较基线降低9.39%、心血管不良事件风险降低20%（HR=0.80），尤其是心肌梗死风险降低28%（HR=0.72）。该研究结果提示，GLP-1RA心血管保护作用与减重相关，而非降糖作用。荟萃分析结果表明，GLP-1RA可将糖尿病合并心血管高风险患者的心力衰竭住院率降低约10%。但关于GLP-1RA降低心力衰竭住院风险的研究结果并不完全一致。FIGHT试验纳入因急性心力衰竭住院的射血分数降低的心力衰竭患者300例。所有患者中位左心室射血分数为25%；82%患有缺血性心脏病、59%患有2型糖尿病。结果显示，利拉鲁肽组与安慰剂组死亡（HR=1.10）和心力衰竭再住院（HR=1.30）风险无显著差异，不同糖尿病状态亚组分析结果也相似。因此，关于射血分数降低的心力衰竭患者能否从GLP-1RA用药中获益，仍有待更多证据进行验证。GLP-1RA改善肾脏结局获益的证据多来源于次要结局或探索性分析，其机制可能与大量蛋白尿进展抑制有关，但对其他临床重要肾脏终点的影响尚不明确，包括肾小球滤过率（eGFR）下降速度、开始肾脏替代治疗的时间等。FLOW试验评估皮下注射司美格鲁肽对2型糖尿病患者慢性肾病影响，研究纳入患者3533例，随机接受司美格鲁肽或安慰剂治疗。主要结局为首次肾功能衰竭的时间（持续eGFR<15 ml/min/1.73m2或开始慢性肾脏替代治疗）。研究结果显示，司美格鲁肽组eGFR较基线下降≥50%或因肾脏或心血管原因死亡风险较低（HR=0.76）。肾脏替代治疗的开始时间延迟，但未达到统计学意义（HR=0.84）。因此，司美格鲁肽或可影响2型糖尿病合并慢性肾病患者的临床肾脏终点。GLP-1RA和SGLT-2i的潜在互补证据一项比较GLP-1RA与SGLT-2i疗效的荟萃分析中，纳入5项GLP-1RA相关和3项SGLT-2i相关试验，涉及77242例患者。与安慰剂组相比，GLP-1RA组的心血管不良事件风险降低了12%（HR=0.88），SGLT-2i组的心血管不良事件风险降低了11%（HR=0.89），这表明GLP-1RA和SGLT-2i降低心血管不良事件风险的程度相似。此外，多项荟萃分析结果显示，无论是否患有糖尿病，SGLT2i在射血分数降低的心力衰竭和射血分数保留的心力衰竭中都能将心力衰竭住院降低约30%。GLP-1RA联合SGLT-2i能否进一步降低糖尿病患者的心血管和肾脏事件的发生？理论上来说是可行的，但尚缺乏相关试验来直接验证联合疗法的效果。此前，AMPLITUDE-O试验和Harmony Outcomes试验分别有15.2%（n=618）和6.1%（n=575）的患者在基线时使用SGLT-2i。AMPLITUDE-O试验事后分析发现，基线时SGLT-2i使用者和未使用者的心血管不良事件风险分别降低了30%和26%（HR=0.70和0.74，相互作用P=0.70）、心力衰竭住院风险分别降低了77%和30%（HR=0.23和0.70，相互作用P=0.35）、复合肾脏结局风险分别降低了48%和30%（HR=0.52和0.70，相互作用P=0.38）。Harmony Outcomes试验事后分析未对肾脏结局进行探讨，但也观察到了类似的结果。DECLARE-TIMI 58试验中，4.4%患者基线时使用GLP-1RA，结果显示，SGLT-2i（达格列净）可降低心血管不良事件、心力衰竭住院和复合肾脏结局的风险，这种作用与基线是否使用GLP-1RA无关。从现有研究来看，GLP-1RA和SGLT-2i的作用机制基本上是独立的，但仍需要进一步研究，以评估二者联合治疗是否能够带来更大的临床益处。GLP-1RA+SGLT-2i+非奈利酮的三联治疗策略FIDELIO-DKD、FIGARO-DKD及FIDELITY试验表明，非奈利酮可减少慢性肾病合并糖尿病患者的心血管和肾脏事件发生率，这主要得益于非奈利酮可降低心力衰竭住院风险。这3项大型临床试验的FINE-HEART汇总分析中，非奈利酮降低了心力衰竭住院、白蛋白尿进展复合终点（排除心血管事件影响）、心血管不良事件和全因死亡的风险。参与者中，基线分别有5.8%和8.9%的患者使用GLP-1RA和SGLT-2i，无论这些药物的使用情况如何，非奈利酮对心血管死亡的治疗效果都是一致的。非奈利酮对心血管和肾脏事件的临床益处也不太可能受到GLP-1RA或SGLT-2i联合治疗的影响。但关于非奈利酮联合GLP-1RA和SGLT-2i的附加作用的临床证据仍然有限。有学者将GLP-1RA、SGLT-2i和非奈利酮的相关临床试验数据进行交叉试验分析，以估计三联治疗的效果。研究结果显示，在糖尿病和蛋白尿患者中，相比于常规治疗，三联治疗组的心血管不良事件、心力衰竭住院和慢性肾病进展的风险分别降低了35%（HRs=0.65）、55%（HRs=0.45）和58%（HRs=0.42）。从结果来看，潜在原因是GLP-1RA、SGLT-2i和非甾体MRA的作用机制通常互补和独立、可能部分重叠。因此，这三类药物结合时的效果可能相加。此外，研究还发现，对于50岁以上的患者，相比于单独使用常规疗法，采用三联疗法治疗的患者心血管不良事件、心力衰竭住院和慢性肾病的无事件生存期分别延长了3.2年、3.2年和5.5年。这提示，相比传统疗法或单独用药，GLP-1RA、SGLT-2i和非奈利酮的三联疗法具有更强的心肾保护作用。鉴于现有证据，三联疗法有望提供额外的心脏保护，但需要开展进一步的随机对照试验，以明确三联疗法是否具有相加或协同作用。总结和未来前景联合用药可能进一步增强治疗效果，根据患者情况选择合适药物是未来心血管-肾脏代谢综合征领域的精准治疗方向。2型糖尿病和/或肥胖患者可能受益于联合用药，并改善心血管和肾脏结局。GLP-1RA+SGLT-2i+非奈利酮的方案，可能在心血管和肾脏保护方面具有互补作用。但治疗策略的制定仍需考虑到以下几方面的差异：1）明确从联合治疗中获益的人群；2）明确加强治疗的理想时机和优先级，因为目前的证据不足以弥补这一空白；3）患者接受联合治疗如何维持长期依从性和安全性。本文作者：泰达国际心血管病医院 郑刚推荐阅读欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料（可上下滑动查看）[1] Wong ND, Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nat Rev Cardiol. 2023;20(10):685–95. [2] Vaduganathan M, Mensah GA, Turco JV, et al. The global burden of cardiovascular diseases and risk: a compass for future health. J Am Coll Cardiol. 2022;80(25):2361–71. [3] Cea Soriano L, Johansson S, Stefansson B, et al. Cardiovascular events and all-cause mortality in a cohort of 57,946 patients with type 2 diabetes: associations with renal function and cardiovascular risk factors. Cardiovasc Diabetol. 2015;14:38. [4] de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022;45(12):3075–90. [5] American Diabetes Association Professional Practice C: 11. Chronic kidney disease and risk management: standards of care in diabetes-2024. Diabetes Care 2024, 47(Suppl 1):S219-S230. [6] Bornfeldt KE. Does elevated glucose promote atherosclerosis? Pros and Cons Circ Res. 2016;119(2):190–3. [7] Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93. [8] Ueki K, Sasako T, Okazaki Y, et al. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial. Lancet Diabetes Endo crinol. 2017;5(12):951–64. [9] Gaede P, Lund-Andersen H, Parving HH, et al. Effect of a mul tifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91. [10] Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Associa tion (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–86. [11] Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474–84. [12] Bjorkegren JLM, Lusis AJ. Atherosclerosis: recent developments. Cell. 2022;185(10):1630–45. [13] Abel ED, Gloyn AL, Evans-Molina C, et al. Diabetes mellitus-progress and opportunities in the evolving epidemic. Cell. 2024;187(15):3789–820. [14] Ritchie RH, Abel ED. Basic mechanisms of diabetic heart disease. Circ Res. 2020;126(11):1501–25. [15] van Raalte DH, Bjornstad P, Cherney DZI, et al. Combination therapy for kidney disease in people with diabetes mellitus. Nat Rev Nephrol. 2024;20(7):433–46. [16] Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. [17] Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular out comes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. [18] Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-con trolled trial. Lancet. 2018;392(10157):1519–29. [19] Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo controlled trial. Lancet. 2019;394(10193):121–30. [20] Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896–907. [21] Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovas cular benefits and mechanisms of action. Nat Rev Cardiol. 2023;20(7):463–74. [22] Giugliano D, Scappaticcio L, Longo M, et al. GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. Cardiovasc Diabetol. 2021;20(1):189. [23] Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653–62. [24] Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57. [25] Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221–32. [26] Sawami K, Tanaka A, Node K. Anti-obesity therapy for cardiovascular disease prevention: potential expected roles of glucagon-like peptide-1 receptor agonists. Cardiovasc Diabetol. 2022;21(1):176. [27] Margulies KB, Hernandez AF, Redfield MM, et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016;316(5):500–8. [28] Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19(1):69–77. [29] Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069–84. [30] Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med. 2024;390(15):1394–407. [31] Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109–21. [32] Kosiborod MN, Deanfield J, Pratley R, et al. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024;404(10456):949–61. [33] Petrie MC, Borlaug BA, Butler J, et al. Semaglutide and NT-proBNP in obesity-related HFpEF. J Am Coll Cardiol. 2024;84(1):27–40. [34] Verma S, Petrie MC, Borlaug BA, et al. Inflammation in obesity-related HFpEF: The STEP-HFpEF Program. J Am Coll Cardiol. 2024;84(17):1646–62.免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。分享，点赞，在看，传递医学新知
临床结果临床成功
100 项与 度拉糖肽 相关的药物交易
登录后查看更多信息
研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
登录
| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 2型糖尿病 | 美国 | 2014-09-18 |
未上市
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 低血糖 | 临床3期 | 日本 | 2021-04-13 | |
| 慢性肾病 | 临床3期 | 美国 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 巴西 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 匈牙利 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 墨西哥 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 波兰 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 罗马尼亚 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 南非 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 西班牙 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 乌克兰 | 2012-07-01 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
N/A | 非小细胞肺癌 III期 PD-L1 positive | 42 | 夢窪窪廠遞願鹽網製衊(構壓憲構簾餘獵壓簾鹹) = 鹹繭製築淵衊衊夢鏇餘 鹽積蓋壓鏇廠蓋蓋獵鹹 (糧齋獵憲鹹獵淵築繭範 ) 更多 | 积极 | 2025-03-26 | ||
临床2期 | 255 | Dulaglutide 1.5mg | 淵觸壓鬱構壓遞窪鬱糧(獵觸鹹簾夢遞窪鬱網製) = systolic blood pressure was stable over the period of 52 weeks after smoking cessation 願醖醖糧願鑰築壓壓蓋 (繭構齋窪鹽糧範夢遞獵 ) | - | 2025-03-03 | ||
临床4期 | 212 | 鏇網鹹餘獵齋憲餘膚廠 = 衊醖鬱鏇繭憲窪遞夢鑰 夢構顧積觸淵獵製衊範 (積餘鏇餘簾廠鹽窪夢製, 觸餘遞築構夢衊壓膚繭 ~ 顧膚鬱淵餘顧齋壓餘鏇) 更多 | - | 2025-02-05 | |||
N/A | 30 | 鹽選簾膚淵範衊觸積壓(鹽積糧齋製鏇醖廠鹹襯) = 構齋淵願膚淵鹽繭壓遞 鏇觸觸鬱簾淵鏇衊積積 (製構鏇廠糧糧醖製鏇夢 ) | 积极 | 2025-01-23 | |||
N/A | 晚期胆道癌 一线 | - | 夢鹽夢廠構網構簾蓋繭(鹽鹹構鹹艱鏇範構憲構) = All patients experienced adverse events (AEs), addition of lenvatinib does not increase the risk of AEs 鏇廠鹽願鏇鏇網壓獵襯 (範積簾夢製窪顧選築築 ) | 积极 | 2025-01-23 | ||
Durvalumab + Gemcitabine-based chemotherapy | |||||||
N/A | 1,099 | Durvalumab plus chemotherapy | 淵齋憲範製觸廠餘繭選(淵築餘鬱餘廠憲鑰衊廠) = 衊願餘鑰窪鹹鏇憲餘鏇 襯淵鹹餘鹹鏇夢製餘製 (鹽鹽構壓蓋鑰構選糧顧 ) | 积极 | 2025-01-23 | ||
Chemotherapy only | 淵齋憲範製觸廠餘繭選(淵築餘鬱餘廠憲鑰衊廠) = 夢鏇獵鹹壓選鏇糧蓋鏇 襯淵鹹餘鹹鏇夢製餘製 (鹽鹽構壓蓋鑰構選糧顧 ) | ||||||
N/A | 50 | 壓獵憲夢獵範蓋艱鑰築(積範鬱餘繭蓋鏇顧範顧) = Most AEs were related to chemotherapy, there were 10% immune related AEs 網鑰衊顧鏇選網獵廠膚 (鬱鹹鑰鏇衊築積築憲艱 ) | 积极 | 2025-01-23 | |||
N/A | - | 108 | Durvalumab + Tremelimumab | 糧鏇膚廠選鏇鏇繭夢衊(鏇繭範窪獵鑰衊觸製選) = 構淵餘窪網簾艱構壓遞 積鑰鑰製齋鬱齋範鏇範 (繭鏇夢遞積顧選齋遞網, 27.5 ~ 65.1) 更多 | 积极 | 2025-01-23 | |
願構艱遞憲製憲襯鏇觸(壓鏇願膚觸製網膚製鏇) = 網蓋齋鹹網獵壓廠簾構 選壓齋鹹鹽鹹齋膚衊夢 (淵膚構簾鹹網壓壓壓積, 6.0 ~ 12.1) 更多 | |||||||
临床4期 | 16 | Continuous glucose monitor (CGM), blinded+Dulaglutide (Dulaglutide) | 壓糧糧鑰選願衊窪餘襯(艱簾壓襯積選糧廠鏇繭) = 夢蓋獵鏇鏇醖獵淵觸鑰 蓋廠衊積糧艱壓網醖願 (築廠鬱齋淵鹹淵廠廠夢, 19.70) 更多 | - | 2025-01-17 | ||
Continuous glucose monitor (CGM), blinded (Placebo) | 壓糧糧鑰選願衊窪餘襯(艱簾壓襯積選糧廠鏇繭) = 鬱築廠鏇築糧壓鹽選壓 蓋廠衊積糧艱壓網醖願 (築廠鬱齋淵鹹淵廠廠夢, 27.26) 更多 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
生物类似药
生物类似药在不同国家/地区的竞争态势。请注意临床1/2期并入临床2期，临床2/3期并入临床3期
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
来和芽仔聊天吧
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用