To perform an observational analysis to emulate a target trial (i.e., a hypothetical pragmatic trial that would have answered the causal question of interest) comparing the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU), at the class and individual agent level, in head-to-head comparisons in patients with type 2 diabetes (T2D).

开始日期2021-08-01

申办/合作机构

The Brigham & Women's Hospital, Inc.

[+3]

NCT03015519

/ Withdrawn临床3期

A Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Albiglutide for the Treatment of Type 2 Diabetes Mellitus in Pediatric Patients

The incidence of Type 2 Diabetes Mellitus (T2DM) is increasing day by day but the treatment options are limited in children and adolescents. Albiglutide, approved for the treatment of T2DM in adult population, is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. The study will be conducted in 2 parts: Part A is a single dose pharmacokinetic (PK) study to confirm the dose and safety of albiglutide in pediatric subjects aged 10 to less than 18 years and Part B is a randomized double-blind placebo controlled study to evaluate the safety and efficacy (glycemic control) of albiglutide in the pediatric population. Treatment duration in Part B is 52 weeks (24 weeks double-blind placebo-controlled and 28 weeks open-label during which all subjects will receive albiglutide). Approximately 210 eligible male and female subjects will be included in the study.

开始日期2017-08-14

申办/合作机构

GSK Plc

NCT02750930

/ Terminated临床4期

An Open-label Extension to Study 200952 to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of Albiglutide Liquid Drug Product in Subjects With Type 2 Diabetes Mellitus

Albiglutide has been developed for the treatment of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise, as monotherapy, or in combination with existing therapies and has been approved by the United States (US) Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other regulatory agencies. This is a 26 week, open-label, single group, multicenter, extension study to Study 200952. This extension study will provide extended safety, tolerability and immunogenicity data for the albiglutide liquid drug product. This extension study will comprise 2 study periods: treatment (26 weeks) and post-treatment follow-up (8 weeks). A maximum of 300 subjects will be eligible to take part in this extension study.

开始日期2016-10-07

申办/合作机构

GSK Plc

100 项与阿必鲁肽相关的临床结果

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100 项与阿必鲁肽相关的转化医学

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100 项与阿必鲁肽相关的专利（医药）

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项与阿必鲁肽相关的文献（医药）

2025-08-11·CURRENT PHARMACEUTICAL DESIGN

An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs

Article

作者: Khyat, Nada O. ; Alsubahi, Ramzyah A. ; Alamoudi, Mariam K. ; Alsibyani, Rawan W. ; Zayed, Mohamed F. ; Alshami, Rahaf Z.

Introdcution::

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity.

Methods::

The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria.

Result::

They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties.

Discussion::

The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties.

Conclusion::

GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features.

2025-08-01·JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists

Article

作者: Federici, Massimo ; Angiolillo, Dominick J ; Bernardi, Marco ; Sciarretta, Sebastiano ; Simeone, Beatrice ; Benenati, Stefano ; Ortega-Paz, Luis ; Rocco, Erica ; Greco, Ernesto ; Spadafora, Luigi ; Mehran, Roxana ; Crea, Filippo ; Laudani, Claudio ; Sarto, Gianmarco ; Frati, Giacomo ; D'Amario, Domenico ; Galli, Mattia

BACKGROUND:

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined.

OBJECTIVES:

Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods.

METHODS:

Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively.

RESULTS:

A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis, or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles.

CONCLUSIONS:

GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals. (PROSPERO [GLP-1 RAs Reduce Mortality and Cardiovascular Events Across the Spectrum of Treated Patients: A Systematic Review and Meta-Analysis; CRD420251032222]).

2025-04-01·Health Science Reports

Exploring Glucagon‐Like Peptide‐1 Receptor Agonists Usage Among Non‐Diabetic Healthcare Providers: A Cross‐Sectional Multi‐Country Study

Article

作者: Abukhadijah, Hana J. ; Ibraheem, Anas ; Karavadi, Vidusha ; Aldosari, Nasser M. ; Rehman, Obaid Ur ; Nashwan, Abdulqadir J. ; Aljariri, Adham A. ; Abu Asal, Mohammad A. ; Khedr, Mahmoud A. ; Fatima, Eeshal ; Shaban, Mostafa ; Agga, Abdulkarim O. ; Abutaima, Rana ; Aqtam, Ibrahim ; Alomari, Albara M. ; Shaban, Marwa M. ; Barakat, Muna ; Palanivelu, Prakash ; Bastaki, Kholoud ; Al‐Lobaney, Nabeel F. ; Othman, Mutaz I. ; Abujaber, Ahmad A.

ABSTRACT:

Background and Aim:

Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) were initially developed for type 2 diabetes but have gained widespread use for weight management, including among non‐diabetic individuals. This study aimed to estimate the prevalence of GLP‐1RA use, describe usage patterns, and explore healthcare providers' (HCPs) perceptions of their efficacy and safety.

Methods:

A cross‐sectional study was conducted among 657 HCPs from 10 countries using a structured online survey between September and December 2023. Convenience sampling was employed, statistical analyses were performed using STATA 17. Associations between demographic characteristics and perceptions of GLP‐1RAs were analyzed using the chi‐square test.

Results:

Among 657 HCPs, 59.2% were female and 40.8% were male, with a median age of 36.0 years (IQR: 29.0–44.0) and a median BMI of 26.7 (IQR: 23.8–30.7). Among professional groups, nurses accounted for 44.7%, followed by physicians (36.2%) and allied health professionals (18.7%). Semaglutide (45.7%, 95% CI: 41.8%−49.5%) was the most commonly used GLP‐1RA, followed by Liraglutide (36.9%, 95% CI: 33.2%−40.8%). Other GLP‐1RAs were used less frequently, including Dulaglutide (17.0%, 95% CI: 14.2%−20.1%), Exenatide (14.1%, 95% CI: 11.5%−17.0%), Albiglutide (7.0%, 95% CI: 5.1%−9.2%), and Lixisenatide (8.5%, 95% CI: 6.5%−10.9%. Regarding perceived safety, 68.6% considered GLP‐1RAs safe. Safety perceptions were significantly associated with educational level (p = 0.022), with participants holding higher degrees being more likely to perceive GLP‐1RAs as unsafe (18.3%) compared to those with a bachelor's degree or lower (10.8%). No associations were found with age (p = 0.487), sex (p = 0.729), or BMI (p = 0.089). Similarly, 73.5% of participants considered GLP‐1RAs effective for perceived efficacy. No associations were found with sex (p = 0.663) or BMI (p = 0.446). Older participants (p = 0.011) and those with higher education (p = 0.006) were more likely to perceive GLP‐1RAs as ineffective.

Conclusion:

This study provides the first prevalence estimate of GLP‐1RA use among HCPs and GLP1‐Ras users and explores the associations between demographic characteristics and perceptions of safety and efficacy. The findings highlight the self‐prescribing practices of these medications for weight management and underscore the need for appropriate monitoring to avoid potential health risks.

项与阿必鲁肽相关的新闻（医药）

2025-06-02

·国际糖尿病idiabetes

GLP-1奠基人Daniel J. Drucker教授：40年蜕变，勾勒代谢治疗新蓝图！

点击“蓝字”关注我们编者按第二十一届北大糖尿病论坛（PUDF 2025）围绕“GLP-1→∞”这一主题，国内外众多知名学者齐聚一堂，共话胰高糖素样肽-1（GLP-1）领域前沿进展。肠促胰素研究奠基人之一、加拿大多伦多大学Daniel J. Drucker教授回顾了GLP-1类药物研发历程，重点解析司美格鲁肽降糖及心肾保护重要证据，并展望GLP-1领域未来。本文整理核心内容，以期为临床与科研提供参考。一肠促胰素效应及GLP-1作用的早期探索对肠促胰素效应的探索可追溯到1902年促胰液素的发现，之后经过大量研究，1932年正式对其命名。肠促胰素效应是指除了血糖升高的直接刺激作用，摄入葡萄糖等营养物质后还可通过刺激肠道细胞分泌肠源性激素，进而间接促进胰岛β细胞分泌胰岛素[1]。Drucker教授是这方面研究的先驱，其团队40年前就发现血糖升高时GLP-1能够刺激胰岛素分泌及其基因表达，这主要是GLP-1（7-37）小片段的作用[2]。1986年，Nauck等人发现口服葡萄糖较静脉输注能更显著促进胰岛素分泌，而这一肠促胰素效应在2型糖尿病（T2DM）患者中显著减弱（图1）[3]。肠促胰素中有两种重要激素——GLP-1和葡萄糖依赖性促胰岛素多肽（GIP），进食后分别由肠道L细胞和K细胞分泌，通过作用于相应受体，促进胰岛素分泌[4]。图1. T2DM患者中肠促胰素效应减弱早期动物研究显示，GLP-1不仅调节血糖，还可抑制食欲。1996年，多项动物研究证实GLP-1能够抑制摄食量[5-7]，但该作用在GLP-1受体敲除时消失，且GLP-1受体敲除小鼠未出现预期肥胖[7]。回头看，这也提示GLP-1并非体重及食欲控制的唯一激素。二GLP-1类药物的多效性：从单一降糖到多病共治，重塑代谢疾病管理随着研究深入，人们发现GLP-1受体在心脏、肾脏、血管、肝脏、大脑等组织器官广泛表达，具有多效性的心血管代谢作用[8]。目前，GLP-1RA除被证实能为T2DM、肥胖、慢性肾脏病（CKD）患者带来获益，研究也发现其对心肌梗死、心衰、卒中、代谢性肝病、骨关节炎、阻塞性睡眠呼吸暂停等治疗有益[9]。GLP-1RA的多效性作用无论对于医生还是患者都是利好消息，尤其对于多种代谢疾病共存患者，还能够简化治疗方案。01GLP-1RA强效降糖、改善心血管代谢，同时心血管获益显著SUSTAIN系列研究[10-19]显示，司美格鲁肽1.0 mg强效降糖，HbA1c降幅最高达1.8%（图2），显著改善T2DM患者多重心血管代谢危险因素，包括减重、降压、调脂及缩围（图3）。在心血管结局研究SUSTAIN 6研究[20]中，司美格鲁肽显著降低主要心血管不良事件（MACE）风险达26%，显著降低非致死性卒中风险39%。图2. SUSTAIN系列研究：司美格鲁肽1.0 mg强化降糖，HbA1c降幅最高达1.8%图3. SUSTAIN系列研究：司美格鲁肽1.0 mg改善多重心血管代谢危险因素针对包括SUSTAIN 6、FLOW和SOUL在内的10项心血管和肾脏结局研究（n=71,351）的系统回顾和荟萃分析[21]表明，长效GLP-1RA使MACE风险降低14%、心衰住院风险降低14%、复合肾脏结局风险降低17%、全因死亡率降低12%，且安全性良好（图4）。图4.长效GLP-1RA能够改善T2DM患者的心肾结局及死亡率GLP-1RA改善心血管结局的具体机制尚未完全阐明。多项临床研究结果显示，GLP-1RA的心血管保护作用独立于减少低血糖的发生，独立于基线体重指数、血脂水平，独立于降糖、降脂、减重、二甲双胍、他汀类药物和SGLT2i的应用[22]。Drucker教授也提到，一周一次的阿必鲁肽降糖效果弱且几乎不减重，2018年就已撤市，但其在Harmony Outcomes研究[23]中仍能显著降低MACE风险达22%。这同样提示，GLP-1RA的心血管获益可能独立于血糖和体重控制。02FLOW研究改写临床实践：司美格鲁肽为糖尿病肾病提供强力肾脏保护2024年公布的肾脏结局研究FLOW[24]结果表明，在T2DM合并CKD患者中，司美格鲁肽1.0 mg显著降低肾脏复合终点（eGFR持续下降>50%、持续性eGFR<15 ml/min/1.73m2、起始长期肾脏替代治疗、肾性死亡或心血管死亡）风险达24%（图5）。司美格鲁肽的多效性，使其成为糖尿病合并心肾疾病患者的优选药物。图5. FLOW研究：司美格鲁肽1.0 mg显著降低T2DM合并CKD患者肾脏复合终点风险达24%三GLP-1类药物的临床关切20多年临床经验积累也发现GLP-1类药物存在一些不良反应，主要为消化道反应，但会随治疗时间延长而逐渐好转，且并非所有患者都会发生。Drucker教授提到一例因多囊卵巢综合征（PCOS）而无法怀孕的女性，在使用GLP-1类药物减重过程中成功怀孕，这也是近年来被多次报道的“司美宝宝（Ozempic babies）”现象[25]。Drucker教授分析，这可能与减重后排卵改善、GLP-1类药物延缓胃排空同时影响避孕药吸收有关[25]。此类药物说明书指出女性备孕时应提前停药。但基于人群的观察性队列研究发现，与胰岛素治疗相比，围孕期暴露于GLP-1RA的婴儿并未表现出更高的主要先天畸形风险[26]。当然，目前尚无专门针对孕妇的研究，相关登记研究正在开展。对于围术期患者，指南建议术前1周停用GLP-1RA。一项研究[27]则发现，在因急诊手术而不太可能提前停药的T2DM患者中，使用与未使用GLP-1RA患者的术后呼吸系统并发症总体发生率并无显著差异（3.5% vs. 4.0%，P=0.12）。因此，对于使用GLP-1RA的围术期患者，更重要的是评估哪些人有消化道应激风险、需做床旁急诊超声，而非一律停用GLP-1RA。Drucker教授还提到GLP-1RA的一种极罕见的眼部并发症——非动脉炎性前部缺血性视神经病变（NAION）[28]。他表示，NAION迄今尚无准确的ICD编码，且临床研究中未观察到这种现象，仅来自一些眼科医生的病例报告。为了评估司美格鲁肽对于糖尿病视网膜病变（DR）的影响，以DR为主要终点的FOCUS研究[29]正在开展。当肥胖患者主动减重时，减掉的主要是脂肪，但同时也会减掉一部分非脂肪体重。在非脂肪体重中，肌肉约占一半。GLP-1类抗肥胖药物减重效果显著，研究发现其减掉的体重中25%~40%为非脂肪体重。这就引起一些担忧：减重会不会损失太多肌肉，让人身体变弱？然而，这些研究并未直接测量减重后肌肉量的具体变化或评估其对身体功能的客观影响。虽然减重时肌肉的绝对量会随减重总量有所减少，但其减少量占原有肌肉的比例通常较小。更重要的是，肌肉的相对减少幅度远小于脂肪的减少，最终身体功能会得到改善。因此，近期关于GLP-1类药物显著减重导致身体衰弱或肌少症的担忧，目前缺乏足够的数据支持[30]。四研发持续火热，小分子及多靶点药物成焦点GLP-1药物研发仍在火热开展，在神经退行性疾病方面，针对阿尔兹海默病的2项研究有望年底公布结果。未来发展方向聚焦于多重激动剂策略，除靶向GLP-1受体的GLP-1RA外，新兴药物还通过靶向多种受体与通路实现协同作用，包括：激活素Ⅱ型受体（ACVR2）、孤啡肽受体（APLNR）、胰淀素受体（AMLNR）、胰高糖素受体（GCGR）、葡萄糖依赖性促胰岛素多肽受体（GIPR）、胰高糖素样肽-2受体（GLP2R）以及神经肽Y2受体（NPY2R），有望更大程度改善耐受性、更大幅度减重和降糖、简化给药途径和频率、降低成本，以及更有针对性地改善T2DM、肥胖和相关共病患者的预后[31]。五结语从肠促胰素效应的发现，到司美格鲁肽成为首个兼具降糖、护心、保肾多效性的药物，GLP-1类药物的40年历程堪称代谢医学的典范。其心血管保护的独立性、多器官作用的广泛性，以及口服制剂的突破，不断重塑糖尿病治疗格局。我们正站在GLP-1研发的黄金时代，每一次突破都可能改写不计其数的患者命运。希望GLP-1领域未来能够涌现出更多好药，造福广大患者。参考文献（上下滑动可查看）1. 洪天配, 等. 中华内分泌代谢杂志. 2018; 34(8): 629-633.2. Drucker DJ, et al. Proc Natl Acad Sci U S A. 1987; 84(10): 3434-3438.3. Nauck M, et al. Diabetes. 1986; 29(1): 46-52.4. Campbell JE, Drucker DJ. Cell Metab. 2013; 17(6): 819-837.5. Turton MD, et al. Nature. 1996; 379(6560): 69-72.6. Tang-Christensen M, et al. Am J Physiol. 1996; 271(4 Pt 2): R848-5 R86.7. Srocchi LA, et al. Nat Med. 1996; 2(11): 1254-1258.8. Drucker DJ, Holst JJ. Diabetologia. 2023; 66(10): 1765-1779.9. Gonzalez-Rellan, M & Drucker D.J. Cell Rep Medicine. 2025 (in press).10. Sorli C, et al. Lancet Diabetes Endocrinol. 2017; 5(4): 251-260. SUSTAIN 111. Ji L, et al.Diabetes Obes Metab. 2021; 23(2): 404-414. SUSTAIN China12. Ahrén B, et al. Lancet Diabetes Endocrinol. 2017; 5(5): 341-354. SUSTAIN 213. Ahmann AJ, et al. Diabetes Care. 2018; 41(2): 258-266. SUSTAIN 314. Pratley RE, et al. Lancet Diabetes Endocrinol. 2018; 6(4): 275-286. SUSTAIN 715. Lingvay I, et al. Lancet Diabetes Endocrinol. 2019; 7(11): 834-844. SUSTAIN 816. Zinman B, et al. Lancet Diabetes Endocrinol. 2019; 7(5): 356-367. SUSTAIN 917. Capehorn MS, et al. Diabetes Metab. 2020; 46(2): 100-109. SUSTAIN 1018. Aroda VR, et al. Lancet Diabetes Endocrinol. 2017; 5(5): 355-366. SUSTAIN 419. Rodbard HW, et al. J Clin Endocrinol Metab. 2018; 103(6): 2291-2301. SUSTAIN 520. Marso SP, et al. N Engl J Med. 2016; 375(19): 1834-1844. SUSTAIN 621. Lee MMY, et al. Diabetes Care. 2025; 48(5): 846-859.22. 肖诚, 于淼. 中华糖尿病杂志. 2022; 14(12): 1348-1354.23. Hernandez AF, et al. Lancet. 2018; 392(10157): 1519-1529.24. Perkovic V, et al. N Engl J Med. 2024; 391(2): 109-121.25.https://edition.cnn.com/2024/05/08/health/ozempic-babies-pregnancy/index.html26. Cesta CE, et al. JAMA Intern Med. 2024; 184(2): 144-152.27. Dixit AA, et al. JAMA. 2024; 331(19): 1672-1673.28. Hathaway JT, et al. JAMA Ophthalmol. 2024; 142(8): 732-739.29.ttps://clinicaltrials.gov/study/NCT03811561?term=FOCUS&intr=semaglutide&rank=130. Conte C, et al. JAMA. 2024; 332(1): 9-10.31. Drucker DJ. Diabetes Care. 2024; 47(11): 1873-1888.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

临床结果

2025-05-28

·国际糖尿病idiabetes

探秘GLP-1RA心血管保护机制，远不止减重这么简单！︱PUDF 2025

点击“蓝字”关注我们2025年，正值胰高血糖素样肽-1受体激动剂（GLP-1RA）临床应用二十周年。随着临床证据不断积累，以司美格鲁肽为代表的GLP-1RA心血管获益及其治疗价值日益凸显，被指南推荐为2型糖尿病（T2DM）合并动脉粥样硬化性心血管疾病（ASCVD）及其高危因素患者的一线降糖药。GLP-1RA的心血管保护机制一直备受关注，其抗动脉粥样硬化作用进展如何？心血管获益是否依赖于减重作用？在2025年5月23~25日举办的“第二十一届北大糖尿病论坛”上，研究者对这些热点问题进行了深入探讨。一、GLP-1RA的心血管获益证据及特点分析近年来多项心血管结局研究（CVOT）证实，部分GLP-1RA具有明显心血管获益，可显著减少T2DM患者主要心血管不良事件（MACE），包括非致死性心肌梗死、非致死性卒中或心血管死亡的复合终点。以司美格鲁肽为例，SUSTAIN 6研究显示，在ASCVD或ASCVD高风险的T2DM患者中，司美格鲁肽注射液显著降低3P-MACE风险达26%，降低非致死性卒中风险达39%（图1）[1]，还可降低主要冠脉事件（包括心肌梗死、冠脉血运重建术）风险达26%[2]。真实世界研究进一步印证了CVOT结果，司美格鲁肽降低T2DM合并ASCVD患者的2点MACE（包括缺血性卒中和心肌梗死）及其两组分风险分别达40%、46%、36% [3]。图1. 司美格鲁肽显著降低3P MACE和卒中风险值得注意的是，GLP-1RA心血管获益主要由ASCVD相关事件风险降低所驱动。荟萃分析显示，不同于SGLT2i，GLP-1RA可显著降低包括卒中在内的MACE全部三组分[4,5]，提示其抗动脉粥样硬化作用更为突出。2023年《胰高血糖素样肽-1受体激动剂防治成人2型糖尿病合并动脉粥样硬化性心血管疾病的中国专家共识》指出，GLP-1RA主要改善与动脉粥样硬化相关的临床结局如心肌梗死、卒中及其导致的死亡[6]。目前认为，GLP-1RA的心血管保护作用可能通过多种路径实现，除降糖、降压、调脂、减重等间接作用外，还可直接干预动脉粥样硬化的发生发展。探讨GLP-1RA的抗动脉粥样硬化作用，还得从T2DM与ASCVD的发生机制说起。二、从ASCVD发生机制看GLP-1RA的抗动脉粥样硬化作用T2DM与动脉粥样硬化的发生发展ASCVD以动脉粥样硬化为核心病理生理机制，包括冠状动脉性心脏病、脑血管病与外周动脉疾病在内的一系列疾病。动脉粥样硬化是逐渐进展的病变，涉及多种机制，而糖尿病与动脉粥样硬化形成中的多个环节密切相关，在动脉粥样硬化发生发展过程中起到一定促进作用[7]。例如，糖尿病患者常合并多种心血管危险因素，如高血糖、高血压、血脂异常等，共同促进动脉粥样硬化进展[8]；糖尿病在发病过程中引发的氧化应激和非感染性慢性炎症也会导致动脉粥样硬化的发生发展[9]。而且，糖尿病大血管病变的本质也是动脉粥样硬化[9]。临床上，糖尿病常与ASCVD相伴发生，约三分之一T2DM患者合并心血管疾病，其中95%为ASCVD[10]。由此可见，抗动脉粥样硬化作用对于改善患者预后极为重要，而这可能也正是GLP-1RA心血管获益的重要机制。GLP-1RA的抗动脉粥样硬化作用基础和临床研究显示，GLP-1RA可能通过多机制、多途径来抑制动脉粥样硬化的发展，稳定斑块，包括降低低密度脂蛋白胆固醇（LDL-C）水平、改善内皮功能、减少黏附分子表达和抑制巨噬细胞聚集、抑制平滑肌细胞增殖与迁移等（图2）[7]。图2. GLP-1RA通过多种机制抑制动脉粥样硬化发展，稳定斑块降低血脂：以LDL-C升高为主的血脂异常是ASCVD发生发展的首要危险因素。SUSTAIN系列研究中，司美格鲁肽表现出良好的降脂作用，尤其是1.0mg剂量组。SUSTAIN 1研究中，采用司美格鲁肽1.0mg的患者LDLC与甘油三酯显著低于安慰剂组；SUSTAIN 9研究中，司美格鲁肽1.0mg较安慰剂显著降低LDL-C、总胆固醇和甘油三酯水平[11]。改善内皮功能：内皮功能障碍是动脉粥样硬化斑块形成的早期重要机制。基础研究证实，GLP-1RA可显著减轻氧化LDL（ox-LDL）诱导的血管内皮损伤，减少内皮通透性增加，促进NO生成；促进内皮依赖性血管扩张，改善内皮舒张功能；并减少内皮黏附分子表达[12-14]。抑制单核/巨噬细胞聚集：在动脉粥样硬化形成过程中，单核细胞被招募到受损的内皮细胞，随后分化为巨噬细胞，吞噬修饰脂蛋白，转化为富含胆固醇的泡沫细胞，后者聚集成簇形成坏死核，最终导致粥样硬化斑块形成[15]。动物研究显示，GLP-1RA可抑制单核/巨噬细胞聚集，减少ox-LDL诱导的泡沫细胞形成[16]。抑制血管平滑肌细胞增殖和迁移：在动脉粥样硬化进展期间，血管平滑肌过度增殖并迁移到内膜中。体外研究发现，GLP-1RA能抑制高血糖诱导的血管平滑肌增殖和迁移，提示其可能作用于动脉粥样硬化的这一重要病理生理过程[17]。增加纤维帽厚度，稳定斑块：晚期动脉粥样硬化病变包含一层纤维结缔组织，称为纤维帽，纤维帽的厚度直接影响动脉粥样硬化斑块的稳定性。基础研究显示，GLP-1/GLP-1RA显著增加纤维帽厚度，稳定斑块[18,19]。此外，GLP-1RA还可通过抑制炎症反应、抑制血小板聚集来发挥抗动脉粥样硬化作用。临床研究表明，GLP-1RA显著缩小T2DM患者颈动脉斑块面积，改善动脉僵硬度[20,21]。纳入19项RCT的荟萃分析显示，GLP-1RA显著降低心梗后患者心肌梗死的面积[22]。以上证据一致支持，GLP-1RA对动脉粥样硬化形成的各个环节发挥改善作用，这为其心血管获益机制提供了可能的解释。三、GLP-1RA可改善多重代谢风险因素，其心血管获益与减重相关性成关注热点除直接抗动脉粥样硬化作用外，GLP-1RA还可改善多重代谢风险因素，通过降糖、降压、减重等来改善ASCVD的危险因素，早期阻断心血管事件链，有助于减少心血管不良事件的发生。SUSTAIN系列研究证实，司美格鲁肽1.0mg可显著降低T2DM患者的HbA1c达1.8%，减轻体重达6.5 kg，缩小腰围达6.0 cm，降低收缩压达7.3 mmHg，并全面改善血脂谱（图3）[23-30]。图3. 司美格鲁肽1.0mg改善多重心血管代谢因素在GLP-1RA的多重代谢获益中，减重作用尤为突出。关于GLP-1RA心血管获益与减重效应之间的关联，也因此而备受关注。通过对多项CVOT数据的进一步分析，目前观点普遍认为，体重变化无法完全解释GLP-1RA的心血管保护作用。既往研究发现，在超重/肥胖患者中，体重显著降低≥10%才会得到心血管获益[31]。然而并非所有GLP-1RA都有显著的减重效果，例如阿必鲁肽减重效力一般，其在CVOT（Harmony研究）中仍被证实具有明确的MACE获益[32]。即使是减重效果出色的司美格鲁肽，减重效应也不能完全解释其心血管获益。SELECT研究中，司美格鲁肽2.4mg组与安慰剂组的MACE曲线在治疗早期即出现分离，远早于减重达到最大降幅的时间，在SELECT研究后期当减重水平到达平台期后，心血管获益仍在持续[33]；SUSTAIN 6研究中，司美格鲁肽1.0mg与安慰剂的MACE曲线分离随着时间延长而不断加大[1]，这些证据都提示司美格鲁肽的MACE风险降低并不完全依赖于减重效应。REWIND研究中，度拉糖肽的MACE获益与其降糖和减少白蛋白尿效应部分相关，但与体重变化无关[34]。以上证据一致支持，GLP-1RA的心血管获益并非完全由减重效应所驱动。四、结语以司美格鲁肽为代表的GLP-1RA对心血管具有明确保护作用，这可能是通过多种路径实现的，包括改善血糖、血糖、血脂、超重/肥胖等ASCVD风险因素，同时可直接抑制动脉粥样硬化进展、稳定斑块，从而改善与动脉粥样硬化相关的临床结局如心肌梗死、脑卒中等。值得注意的是，司美格鲁肽的心血管获益独立于减重效果，无论T2DM患者是否合并超重/肥胖以及体重降幅如何，都能从中获益。对于合并ASCVD或其高风险的T2DM患者，尽早应用司美格鲁肽可早期中断心血管事件链，抑制动脉粥硬化发生发展，减少终末心血管事件，从而改善远期结局。临床实践中，GLP-1RA和SGLT2i均可改善T2DM患者的心血管结局，基于目前循证和指南推荐，SGLT2i主要改善与心衰相关的结局，而GLP-1RA主要改善ASCVD相关结局，可根据T2DM患者临床情况进行个体化选择，对于T2DM合并ASCVD或其高风险患者，有心血管获益证据的GLP-1RA为优选一线降糖药。参考文献（上下滑动可查看）1.Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844.2.Kolkailah AA, et al. Diabetes ObesMetab. 2023; 25(4): 1117-1120.3.De Havenon AH, et al. Abstract WP229 presented at ISC 2024, Feb 7-9, Phoenix, Arizona.4.Sattar N et al. Lancet Diabetes Endocrinol. 2021 Oct;9(10):653-662. 5.Darren K McGuire, et al. JAMA Cardiol. 2021 Feb 1;6(2):148-158.6.中国心血管代谢联盟, 等. 临床心血管病杂志. 2023;39(9):651-660.7.J Atheroscler Thromb, 2017; 24: 227-239.8.Joseph A. Vita, et al.Circulation. 2002;106(2):164-166. 9.吕晓希,等. 中华糖尿病杂志, 2023, 15(5): 383-386.10.Hong T, et al. Diabetes Ther. 2022 May;13(5)969-981.11.纪立农.中华糖尿病杂志. 2023,15(12):1177-1184.12.Wen Yue, et al. IUBMB Life. 2019;71(9):1347-1354.13.Gaspari T et al. Diab Vasc Dis Res. 2011 Apr;8(2):117-24.14.Hattori Y et al., Diabetologia. 2010 Oct;53(10):2256-63.15.程警霈,等.赣南医学院学报. 2023;43(05):435-441.16.Tashiro Y, et al. Peptides.2014; 54:19-26.17.Shi et al. Cardiovascular Diabetology. 2015; 14:18.18.Burgmaier M, et al. Atherosclerosis. 2013 Dec;231(10):427-435. 19.Gaspari T, et al. Diabetes and Vascular Disease Research.2013;10(4): 353-360.20.张岩等，临床合理用药.2018;5(11):37-38. 21.Lambadiari V, et al. Cardiovasc Diabetol. 2018 Jan 8;17(1):8. 22.Wong SY, et al. Cardiovasc Drugs Ther. 2022 Jul 1.23.Sorli C, et al. Lancet Diabetes Endocrinol. 2017;5(4):251-260.24.Ji L, et al. Diabetes Obes Metab. 2021;23(2):404-414.25.Ahmann AJ, et al. Diabetes Care. 2018;41(2):258-266.26.Aroda VR, et al. Lancet Diabetes Endocrinol. 2017;5(5):355-366.27.Rodbard HW, et al. J Clin Endocrinol Metab. 2018;103(6):2291-2301. 28.Pratley RE, et al. Lancet Diabetes Endocrinol. 2018;6(4):275-286.29.Lingvay I, et al. Lancet Diabetes Endocrinol. 2019;7(11):834-844.30.Zinman B, et al. Lancet Diabetes Endocrinol. 2019;7(5):356-367.31.Look ARG, et al. Lancet Diabetes Endocrinol. 2016;?4(11): 913-921.32.Hernandez AF, et al. Lancet. 2018;392:1519-1529.33.Lincoff MA, et al. N Engl J Med. 2023;389:2221-2232.34.Konig, et al. Cardiovasc Diabetol. 2021; 20:194.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

临床结果

2025-04-13

·医学新视点

糖尿病患者心肾风险降低多达58%！三联疗法或为临床治疗新选择

▎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. 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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. 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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 项与阿必鲁肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08843	阿必鲁肽	A10BJ04	DB09043

研发状态

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适应症	国家/地区	公司	日期
2型糖尿病	欧盟	GlaxoSmithKline Trading Services Ltd.	2014-03-20
2型糖尿病	冰岛	GlaxoSmithKline Trading Services Ltd.	2014-03-20
2型糖尿病	列支敦士登	GlaxoSmithKline Trading Services Ltd.	2014-03-20
2型糖尿病	挪威	GlaxoSmithKline Trading Services Ltd.	2014-03-20

未上市

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适应症	最高研发状态	国家/地区	公司	日期
1型糖尿病	临床2期	法国	GSK Plc	2014-10-10
1型糖尿病	临床2期	德国	GSK Plc	2014-10-10
1型糖尿病	临床2期	意大利	GSK Plc	2014-10-10
1型糖尿病	临床2期	西班牙	GSK Plc	2014-10-10
1型糖尿病	临床2期	英国	GSK Plc	2014-10-10
低血糖	临床2期	美国	GSK Plc	2011-12-01
心力衰竭NYHA III级	临床2期	美国	GSK Plc	2010-09-15
心力衰竭NYHA III级	临床2期	英国	GSK Plc	2010-09-15

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO_GU2025	临床3期	前列腺癌	-	GLP-1 receptor agonists (GLP-1RAs)	觸網範醖蓋鬱積鹽憲鑰(膚鹽鏇顧繭製餘繭選衊) = 範築廠壓廠醖夢膚膚製鏇鏇積壓選範鑰顧艱選 (鬱鹽顧艱選夢鏇鬱鑰淵 )	不佳	2025-02-13
				Placebo/non-GLP-1 RA regimens	觸網範醖蓋鬱積鹽憲鑰(膚鹽鏇顧繭製餘繭選衊) = 憲網艱膚鑰餘選餘襯夢鏇鏇積壓選範鑰顧艱選 (鬱鹽顧艱選夢鏇鬱鑰淵 )
NCT02229227 (Pubmed \| Diabetes Care) 人工标引	临床3期	2型糖尿病	814	optimized basal insulin glargine+ lispro+Albiglutide	鹹夢壓糧築網鬱簾醖襯(餘膚鏇築遞鏇衊鏇繭鏇) = 餘鬱選夢築範願選願廠衊窪範願顧壓鹽鹹鹽壓 (簾膚範膚鹽願餘鑰夢鏇, 0.8) 更多	积极	2020-10-01
				optimized basal insulin glargine+ lispro	鹹夢壓糧築網鬱簾醖襯(餘膚鏇築遞鏇衊鏇繭鏇) = 糧鏇鑰夢衊積鬱製獵淵衊窪範願顧壓鹽鹹鹽壓 (簾膚範膚鹽願餘鑰夢鏇, 0.8) 更多
NCT02284009 (Pubmed \| J Clin Endocrinol Metab) 人工标引	临床2期	1型糖尿病	67	insulin+Albiglutide	積鏇願鹹鹹齋顧糧鑰網(艱獵獵製鹽顧膚築鑰鏇) = 艱範觸糧鹽網廠鏇鹽選築糧襯醖壓餘繭鏇鹽繭 (糧鹽憲齋鏇獵壓餘壓製 )	不佳	2020-06-01
				insulin+Placebo	積鏇願鹹鹹齋顧糧鑰網(艱獵獵製鹽顧膚築鑰鏇) = 繭窪積齋觸憲醖憲製鹽築糧襯醖壓餘繭鏇鹽繭 (糧鹽憲齋鏇獵壓餘壓製 )
NCT02660736 (Pubmed)	临床1期	-	59	Albiglutide liquid formulation	顧遞築鑰夢繭願獵窪壓(顧觸築鹹構窪鹽觸鏇網) = 積選築糧壓淵築艱鹽顧顧衊醖鏇夢築顧夢餘網 (壓鏇壓蓋鏇廠廠廠艱餘 ) 更多	-	2019-04-01
				Lyophilized albiglutide	顧遞築鑰夢繭願獵窪壓(顧觸築鹹構窪鹽觸鏇網) = 餘襯齋鬱鑰廠醖築艱鹹顧衊醖鏇夢築顧夢餘網 (壓鏇壓蓋鏇廠廠廠艱餘 ) 更多
NCT02284009 (110933, CTgov)	临床2期	1型糖尿病	67	Insulin (Placebo)	觸餘廠廠製選網廠築範(鹹鹹選餘積衊窪齋構網) = 簾憲窪繭築網憲選憲獵顧襯觸鑰選憲願簾獵遞 (鑰廠醖齋廠艱夢膚窪鬱, 0.366) 更多	-	2019-03-25
				Insulin+Albiglutide weekly injection (Albiglutide)	觸餘廠廠製選網廠築範(鹹鹹選餘積衊窪齋構網) = 選淵網醖艱醖鹽簾鹽壓顧襯觸鑰選憲願簾獵遞 (鑰廠醖齋廠艱夢膚窪鬱, 0.244) 更多
NCT02465515 (CTgov)	临床4期	2型糖尿病	9,463	Albiglutide matching placebo (Placebo)	顧艱襯窪範觸襯繭積構 = 醖鑰遞壓淵窪鑰艱選襯齋選鬱鹽鬱艱壓積醖窪 (積憲顧簾鏇觸衊淵膚選, 遞衊範願餘壓廠製蓋糧 ~ 艱網繭蓋齋鹽觸築窪簾) 更多	-	2019-03-06
				Albiglutide 30 mg (Albiglutide)	顧艱襯窪範觸襯繭積構 = 淵願憲鏇蓋襯積繭築鬱齋選鬱鹽鬱艱壓積醖窪 (積憲顧簾鏇觸衊淵膚選, 遞淵網簾憲夢襯襯選鹽 ~ 積醖夢糧築淵蓋顧襯醖) 更多
NCT02465515 (Pubmed \| Lancet) 人工标引	临床4期	2型糖尿病 \| 心血管疾病	9,463	standard therapy+albiglutide	艱憲齋遞餘繭壓窪繭夢(鏇鏇膚繭選廠齋蓋鹽鹽) = 積積艱鏇選繭餘積鬱壓積構簾獵簾鹽艱壓淵窪 (夢醖選壓憲蓋積夢製遞 ) 更多	积极	2018-10-27
				standard therapy+Placebo	艱憲齋遞餘繭壓窪繭夢(鏇鏇膚繭選廠齋蓋鹽鹽) = 顧構觸窪鹽壓範積糧願積構簾獵簾鹽艱壓淵窪 (夢醖選壓憲蓋積夢製遞 ) 更多
NCT02229227 (200977, CTgov)	临床3期	2型糖尿病	814	Albiglutide+Insulin Glargine (Albiglutide + Insulin Glargine)	製觸糧鹹餘膚膚醖範膚(襯鹹範網範壓繭選鹽獵) = 鹽艱淵憲衊襯膚膚範襯選壓鏇廠顧鹽築願蓋築 (蓋範選窪醖廠遞鹽鬱膚, 0.041) 更多	-	2018-06-29
				Insulin Lispro+Insulin Glargine (Insulin Lispro + Insulin Glargine)	製觸糧鹹餘膚膚醖範膚(襯鹹範網範壓繭選鹽獵) = 襯顧遞餘網顧繭淵願積選壓鏇廠顧鹽築願蓋築 (蓋範選窪醖廠遞鹽鬱膚, 0.040) 更多
NCT02683746 (CTgov)	临床3期	2型糖尿病	308	Lyophilized albiglutide DCC pen injector matching placebo+Albiglutide (Albiglutide Active LAI Plus Placebo Lyophilized DCC PI)	廠窪積餘鹽願觸鏇鹽觸(衊繭範願齋壓醖窪範夢) = 範鹹鹹製鏇夢糧餘繭淵衊製鹽醖築獵糧鹽製網 (醖鬱構壓憲鏇衊醖顧選, 壓鑰積選淵憲淵衊鹹壓 ~ 簾夢鬱獵選壓鏇鹽鑰蓋) 更多	-	2018-05-30
				Albiglutide liquid auto-injector matching placebo+albiglutide (Albiglutide Lyophilized DCC PI Plus Placebo LAI)	廠窪積餘鹽願觸鏇鹽觸(衊繭範願齋壓醖窪範夢) = 願襯鑰顧願獵憲憲膚積衊製鹽醖築獵糧鹽製網 (醖鬱構壓憲鏇衊醖顧選, 窪築鬱觸憲齋鏇蓋餘廠 ~ 製築糧願築憲選觸簾鏇) 更多
NCT02793154 (CTgov)	临床4期	2型糖尿病	4	Exenatide (Part A: Exenatide SC Injection)	鏇選網壓範窪醖鑰鑰網 = 願壓獵網艱餘壓鏇鏇範遞醖願願蓋齋夢鹹襯鹽 (膚蓋窪繭獵衊窪觸鏇醖, 網齋膚蓋蓋齋夢鑰窪網 ~ 醖醖積鹽繭襯鏇構鑰選) 更多	-	2018-05-23
				Exenatide (Part B: Exenatide SC Injection)	鑰願鬱網製廠廠獵窪鏇(鹹鏇願夢糧憲鹹構鑰壓) = 壓壓願衊糧淵衊鑰鬱餘獵窪製蓋蓋蓋蓋繭遞夢 (製襯構築積淵網衊遞夢, 壓鹽簾獵積鬱膚積膚鏇 ~ 夢鑰獵齋鹹窪膚淵願顧) 更多