Effect of Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA) on Alcohol Consumption, Metabolism and Liver Parameters in Patients With Obesity and Fatty Liver Disease

There is evidence that alcoholic beverage consumption significantly interacts with food energy intake. Furthermore, there is accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease. Preclinical and clinical data have showed that GLP-1 RA can decrease alcohol consumption, particularly in obese patients. Moreover there is evidence that liraglutide can improve the liver sinusoidal milieu in pre-clinical models of cirrhosis.
In this study, the investigators aim to assess if patients treated with liraglutide and receiving counselling will achieve a significantly higher alcohol abstinence compared to patients only receiving counselling.

开始日期2025-01-01

申办/合作机构

Insel Gruppe AG

ChiCTR2400088178 / Suspended临床4期IIT

Observation and mechanism of liraglutide in the treatment of obese/overweight patients with type 2 diabetes mellitus complicated with depression

开始日期2024-09-01

申办/合作机构-

NCT06533527 / RecruitingN/AIIT

Randomized Trial of Holding vs. Continuing Incretin-based Therapies Before Upper Endoscopy

To assess whether holding incretin-based therapy before endoscopy reduces the likelihood of clinically relevant Residual Gastric Volume (RGV).
Primary Outcomes:
* Residual gastric volume that precludes adequate endoscopic examination
* Residual gastric volume that necessitates premature termination of the endoscopy procedure
* Need for endotracheal intubation due to stomach contents.
* Occurrence of aspiration events requiring extended observation/monitoring, unplanned therapeutics, and/or hospital admission
Secondary Outcomes:
* Presence of any solid food
* Presence of moderate liquid content
* Increased RGV(Residual Gastric Volume) defined as any amount of solid content or > 0.8 mL/Kg of fluid content (measured from the aspiration/suction canister).
* Differences in primary and secondary outcomes between different medications

开始日期2024-07-31

申办/合作机构

The Cleveland Clinic Foundation

100 项与利拉鲁肽相关的临床结果

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100 项与利拉鲁肽相关的转化医学

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100 项与利拉鲁肽相关的专利（医药）

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4,032

项与利拉鲁肽相关的文献（医药）

2025-03-01·BONE

Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials

Review

作者: Zhang, Yuan ; Wang, Weimin ; Zhu, Dalong ; Jing, Yali ; Chen, Guanhua ; Yang, Donghui

BACKGROUND:

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures.

PURPOSE:

The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes.

METHODS:

A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed.

RESULTS:

A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61-0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for >78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61-0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21-0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments.

CONCLUSION:

GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus.

2025-02-01·JOURNAL OF AFFECTIVE DISORDERS

A systematic review in effects of glucagon-like peptide-1 (GLP-1) mono-agonists on functional connectivity: Target engagement and rationale for the development in mental disorders

Review

作者: Au, Hezekiah C.T. ; Kwan, Angela T H ; Au, Hezekiah C T ; Teopiz, Kayla M. ; Ho, Roger ; Rosenblat, Joshua D ; McIntyre, Roger S ; Kwan, Angela T.H. ; Rosenblat, Joshua D. ; Teopiz, Kayla M ; McIntyre, Roger S. ; Zheng, Yang Jing ; Rhee, Taeho Greg ; Le, Gia Han ; Wong, Sabrina ; Phan, Lee

INTRODUCTION:

The mechanistic role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) in modulating brain functional activity has been inadequately examined. Mental disorders are characterized by dysregulated functional connectivity in brain circuits that subserve phenomenology. We conducted a comprehensive synthesis of known effects of GLP-1 and GLP-1RAs on functional connectivity.

METHODS:

We conducted a systematic review examining studies that investigate changes in functional connectivity mediated by GLP-1 and GLP-1RAs in human adults. Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to April 26, 2024. Primary or secondary studies (n = 8) investigating the role of GLP-1 and GLP-1RAs on functional connectivity were included for analysis.

RESULTS:

GLP-1 and GLP-1RAs modulate functional connectivity within the dorsal default mode network (DMN), visuospatial network, right frontal parietal network, and the salience network. GLP-1 agonism is also associated with decreased functional connectivity within the hypothalamus, lateral orbitofrontal cortex, and amygdala. Contrastingly, some GLP-1RAs (e.g. exenatide) increase functional connectivity in the hypothalamus, nucleus tractus solitarius, and thalamus. Moreover, liraglutide is associated with increased functional connectivity within the hippocampus in healthy individuals suggesting that GLP-1RAs may have differential effects on brain functional connectivity.

DISCUSSION:

We observed that GLP-1 and GLP-1 RAs are associated with changes in functional connectivity known to subserve phenomenology of many mental disorders (e.g. anhedonia). Future research should aim to further examine neural circuits and networks affected by GLP-1 receptor activity and how they may affect cognitive and psychopathological domains in psychiatric disorders.

2025-01-01·Drug delivery and translational research

Microneedle patch with pure drug tips for delivery of liraglutide: pharmacokinetics in rats and minipigs

Article

作者: Chen, Yu ; Yu, Jianghong ; Liu, Jinbin ; Hu, Jingwen ; Hong, Juan ; Xia, Dengning ; Lin, Hongbing ; Yu, Zhiyan ; Hou, Yulin

Transdermal delivery of peptide drugs is almost impossible with conventional penetration enhancers because of epidermal barrier function. Microneedle (MN) patches can bypass the epidermal barrier and have been developed for trans- and intradermal delivery of peptide drugs and vaccines. However, dissolving MN patches are limited by low drug loading capacities due to their small size and admixture of drug and water-soluble excipients. Furthermore, few in vivo pharmacokinetic studies, especially in large animals such as pigs, have been performed to assess post-application systemic drug exposure. Here, we developed a dissolving MN patch with pure liraglutide at the needle tips. The MN patch could load up to 2.21 ± 0.14 mg of liraglutide in a patch size of 0.9 cm², which was nearly two orders of magnitude higher than that obtained with conventional MN patches of the same size. Raman imaging confirmed that liraglutide was localized at the MN tips. The MN had sufficient mechanical strength to penetrate the epidermis and could deliver up to 0.93 ± 0.04 mg of liraglutide into skin with a dosing variability of less than 6.8%. The MN patch delivery enabled faster absorption of liraglutide than that provided by subcutaneous (S.C.) injection, and achieved relative bioavailability of 69.8% and 46.3% compared to S.C. injection in rats and minipigs, respectively. The MN patch also exhibited similar patterns of anti-hyperglycemic effect in diabetic rats and individual variability in pharmacokinetic parameters as S.C. injection. The liraglutide MN application was well tolerated; no skin irritation was observed in minipigs except for mild erythema occurring within 4 h after once daily administration for 7 days at the same site. Our preclinical study suggests that MN patch with pure drug needle tips might offer a safe and effective alternative to S.C. injection for administration of liraglutide.

1,036

项与利拉鲁肽相关的新闻（医药）

2024-12-11

·国际糖尿病idiabetes

机制互补，增效减副：开启糖尿病双靶点协同治疗新时代

点击“蓝字”关注我们在糖尿病治疗领域，近年来不断有新的药物和治疗方法出现，每一次创新都意味着患者生活质量的显著提升。德谷胰岛素利拉鲁肽复方注射剂（IDegLira）作为全球首个基础胰岛素与GLP-1RA联合的复方注射剂，一上市就成为医学界关注的焦点。本文特邀北京大学第一医院内分泌科张杨副主任，深入解析这一新型药物的研发创新、机制获益和临床应用前景。张杨北京大学第一医院毕业于北京大学医学部，医学博士，北京大学第一医院内分泌科副主任，副教授，副主任医师，硕士研究生导师研究方向为自身免疫甲状腺疾病、妊娠内分泌代谢性疾病等，曾获得青年国家自然科学基金、北京自然科学基金、教育部博士点新教师基金、首发优才基金、中华医学会临床医学项目基金等多项基金，曾以第一作者、责任作者身份发表SCI文章、核心期刊论文多篇担任中国女医师糖尿病专委会委员、中国医疗保健国际交流促进会甲状腺疾病分会青年委员、北京医师协会内分泌专科医师分会理事、北京医学会内分泌学分会青年委员全球首创，双靶点协同 IDegLira作为全球首个将基础胰岛素与胰高糖素样肽-1受体激动剂（GLP-1RA）完美结合在一起的复方注射剂，实现了两种药物的强强联合。德谷胰岛素与利拉鲁肽的双组分设计，通过分别作用于胰岛素受体和GLP-1受体，发挥“双靶点协同互补，增效减副”的降糖作用[1-3]。此外，制剂中通过加入苯酚和锌离子的特殊配方及工艺创新，使得两种肽类生物活性分子在制剂中能够保持稳定和共存，互不干扰。凭借其独特的PK/PD特点，IDegLira可发挥长效平稳降糖作用，实现每天1次任意时间注射（图1），大大减少药物注射次数，提高患者的用药依从性和生活质量[4]。图1. 德谷胰岛素利拉鲁肽一支笔，每日一次给药，不受进餐影响，控制全天血糖全球首创，双靶点协同在IDegLira的双受体机制中，德谷胰岛素利拉鲁肽双组分针对2型糖尿病（T2DM）的多重病理生理机制发挥降糖作用（图2）。德谷胰岛素作用于胰岛素受体，通过促进肌肉和脂肪组织葡萄糖摄取，同时抑制肝糖输出，平稳控制空腹血糖（FPG）；而利拉鲁肽则通过作用于胰腺、大脑、胃肠道、肝脏和骨骼肌等组织器官的GLP-1受体，全面降低FPG和餐后血糖（PPG）。更重要的是，两者的联用能够减少胰岛素的使用剂量，进一步降低低血糖和体重增加的风险，为患者带来更为全面的治疗获益[5-7]。图2. 双受体机制互补临床应用前景广阔，开创糖尿病治疗新格局 1 强效降糖 IDegLira在临床应用中的表现同样令人瞩目。2023年美国糖尿病协会（ADA）指南中，将IDegLira分类为降糖效果“非常高（very high）”的降糖药物。在其Ⅲ期临床试验DUAL系列研究中，IDegLira展现了卓越的降糖疗效，糖化血红蛋白（HbA1c）<7%的达标率最高为89.9%，葡萄糖目标范围内时间（TIR）高达90.1%[8-10]。 2 快速达标对 DUAL Ⅰ和Ⅱ研究中0~12周的数据进行分析显示，IDegLira组相较于其单组分组，FPG下降速度更快，实现血糖快速达标。在起始调量期更快使血糖达标，可帮助患者建立治疗信心和自我管理能力，提高患者长期治疗的疗效、安全性及生活质量[11]。 3 疗效持久 2023年ADA指南引用DUAL Ⅷ研究（图3）指出，对于口服降糖药治疗血糖控制不佳的T2DM患者，与起始基础胰岛素相比，起始IDegLira治疗具有更持久的降糖效果，可以帮助克服“临床惰性”，对于改善血糖控制和降低远期并发症风险具有重要意义。图3. DUAL Ⅷ研究的主要终点[12] 4 多重获益 IDegLira治疗还可改善胰岛β细胞功能和心血管风险标志物，包括降低收缩压、低密度脂蛋白胆固醇（LDL-C）、游离脂肪酸和脑钠肽（BNP）水平等，真正实现增“效”减“副”，可能是T2DM患者起始注射治疗的理想选择[13-14]。总结德谷胰岛素利拉鲁肽复方注射剂（IDegLira）的问世，提供了一种全新治疗方案，通过机制互补，疗效实现“1+1>2”，不仅提高患者的治疗满意度，还推动糖尿病治疗领域进步。相信在不久的将来，随着科技持续进步，会有更多像IDegLira这样的创新药物问世，为糖尿病患者带来更加美好、健康的生活。参考文献（上下滑动可查看） [1] Gough SC, et al. Expert Rev Endocrinol Metab. 2016; 11(1): 7-19. [2] Del Prato S. Lancet Diabetes Endocrinol. 2014; 2(11): 856-858. [3] Ceriello A, et al. Nutr Metab Cardiovasc Dis. 2008; 18(4): S17-S33. [4] 母义明, 胡蓓. 临床药物治疗杂志. 2022; 20(6): 16-20. [5] Nakamura T, et al.Diabetologia. 2015; 58(9): 2013-2019. [6] Baggio L, et al. Gastroenterology. 2007; 132(6): 2131-2157. [7] 刘亚丹, 等. 中国新药与临床杂志. 2021; 40(12): 815-821. [8] American Diabetes Association. Diabetes Care. 2023; 46(Suppl_1): S140-S157. [9] Harris SB, et al. Diabetes Obes Metab. 2017; 19(6): 858-865. [10] Philis-Tsimikas A, et al. J Diabetes Sci Technol. 2024; 18(3): 653-659. [11] Vilsbøll T, et al. Clin Drug Investig. 2016; 36(4): 293-303. [12] Aroda VR, et al. Lancet Diabetes Endocrinol. 2019; 7(8): 596-605. [13] Holst J, et al. J Diabetes Sci Technol. 2015; 10(2): 389-397. [14] Vilsbøll T, et al. Diabetes Obes Metab. 2019; 21(6): 1506-1512. 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。

2024-12-10

·PRNewswire

Bask Health: Pioneering Telehealth and Transforming Access to GLP-1 Medications in a Booming Industry

NEW YORK, Dec. 10, 2024 /PRNewswire/ -- The demand for GLP-1 medications is skyrocketing, with studies predicting the market will reach $13.6 billion globally by 2028 (source: Research and Markets). Bask Health is poised to meet this demand through its comprehensive, patient-first approach, offering software to support virtual consultations, medication delivery, pharmacy and doctor network connections. Fueled by advances in technology and shifting patient expectations, the telehealth revolution is reshaping healthcare delivery. A recent report by the Centers for Medicare & Medicaid Services highlights that telehealth services accounted for 32% of all outpatient visits in 2023, signaling a permanent shift in how Americans access care. At the same time, GLP-1 medications—once reserved for niche treatments—have captured national attention as a groundbreaking solution for weight management and metabolic health. Bask Health's telehealth platform seamlessly connects patients to licensed providers specializing in GLP-1 medications like semaglutide and liraglutide, empowering individuals to take control of their health from the comfort of their homes. By leveraging secure technology and providing access to evidence-based treatments, Bask not only increases access to care but also prioritizes the personalized support patients need to achieve lasting results. "Telehealth isn't just a trend—it's the future of healthcare," said Zachary Dorf, CEO and Co-Founder of Bask Health. "We're proud to be at the helm of this movement, delivering safe, effective, and convenient software solutions for doctors and entrepreneurs to help address the nation's wellness. As GLP-1 medications transform outcomes for patients, our mission is to make these life-changing treatments accessible to everyone." As telehealth adoption in the United States reaches unprecedented heights, Bask Health is positioned at the forefront, delivering innovative, patient-focused care through advanced virtual platforms. With telehealth usage surging by over 60% since 2020 (source: McKinsey & Company) and projected to grow into a $225 billion industry by 2030 (source: Global Market Insights), Bask is redefining the healthcare experience for millions. For more information about Bask Health's telehealth solutions and to find out how you can start a telehealth company, visit . SOURCE Bask Health WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-12-10

·氨基观察

GLP-1向AD市场开了一枪？

氨基观察-创新药组原创出品作者 | 武月 GLP-1冲击波，想必大家已经不再陌生。因为不仅仅是减肥、降糖，GLP-1还有能治一切的潜力。密歇根大学安娜堡分校的肥胖专家兰迪·西利甚至说，我们正处在一个将GLP-1药物，视为几乎可以治疗所有疾病的潜在神药的阶段。治疗MASH，改善心血管疾病，减缓糖尿病进展速度，解决睡眠问题，这些还只是开始。科学家们正在研究GLP-1降低阿尔兹海默症（AD）进展的风险，以及抑制成瘾、抑郁症，甚至治疗不孕不育症等等等等。这其中，最受关注的恐怕是阿尔兹海默症。毕竟，这是减肥药之外的另一座庞大的金山。最快明年9月，司美格鲁肽就将读出阿尔兹海默症的全球大三期临床数据。而在此前的临床研究中，其已经初步展现出潜力。今年10月份，发表在《阿尔茨海默氏症与痴呆症》上的一项现实世界研究表明，服用司美格鲁肽的2型糖尿病患者被诊断出患有阿尔茨海默氏症的风险降低了40%至70%。显然，GLP-1已经向AD市场开了一枪。尽管目前支撑这一切的，还只是GLP-1的炎症假说，GLP-1还需要更多证据证明自己，但乐观者已经给出了大胆预测：即使司美格鲁肽的试验只显示出很小的效果，淀粉样蛋白假说也将泡汤了。用一个假说，打败另一个假说（淀粉样蛋白假说）。创新药的世界总是充满惊喜与意外。 / 01 / GLP-1炎症假说众所周知，阿尔茨海默病仍是世界上最困难的疾病之一。核心在于医疗界对于它的发病原理依然知之甚少。目前关于阿尔茨海默病发生机制有两种主流假说：一是，Aβ假说，即β-淀粉样蛋白（Aβ）过度表达聚集成淀粉样斑块；二是，Tau 蛋白假说，即 Tau 蛋白过度磷酸化后错误折叠形成的神经纤维缠结。不管是哪一种假说，都让无数药企频频折戟，包括药企最认可的Aβ假说。按照这一假说，药物对患者大脑中的淀粉样蛋白斑块清除越是完全，对于控制疾病发展就越是有利。已经获批的Donanemab、lecanemab都是如此，不过机制有所不同。这些药物能给患者带来多大好处，还有待时间给出答案。但在乐观情况下，它们顺利获批上市，至少可以证明一点，阿尔茨海默症不再是“研发黑洞”。只要药企能够拿出相对具有说服力的临床数据，监管层并不排斥批准新疗法上市。这对于后来者来说，无疑具有极大的激励作用。这或许，同样适用于GLP-1。因为GLP-1治疗阿尔兹海默症，也是基于一个尚未被证实的机制——炎症假说。今年9月，发表在nauter上的一篇论文，《Why do obesity drugs seem to treat so many other ailments?》，探讨了GLP-1类药物的多种可能益处，以及科学家们对其背后机制的研究进展。其中，就包括炎症假说。一项针对2型糖尿病和慢性肾病患者的临床发现，司美格鲁肽可将严重肾脏并发症（的风险降低 24%。该研究得出结论，肾脏保护机制与参与者体重的变化无关，相反，作者假设这种药物是通过减少肾脏的炎症起作用。已有动物实验表明，作用于GLP-1受体的药物可以抑制肾脏、心脏和肝脏的炎症。这其实有助于解释GLP-1为什么能对MASH产生积极影响。体内有很多地方可以在免疫细胞上找到GLP-1受体，因此这是一条明显的途径。但在一些药物减轻炎症的组织中，周围几乎没有GLP-1受体，去年的一项研究则发现，在这些器官中，大脑中的GLP-1受体很可能是抗炎作用的原因。之所以挖掘GLP-1在帕金森、阿尔茨海默症的潜力，也是从消除炎症角度出发。这两种疾病有个共同特征——神经炎症，且目前疗法无法有效靶向。在这两种疾病中，病理蛋白（阿尔茨海默氏症中的β-淀粉样蛋白、帕金森氏症中的α-突触核蛋白）与大脑中的某些受体相互作用，诱导引起炎症。GLP-1则显示出减轻大脑炎症的能力，有助于关键性生物过程如新神经元生成的进行。 / 02 / 越来越多的证据事实上，此前有研究表明胰岛素抵抗与阿尔茨海默氏症之间存在联系。这一假说甚至导致阿尔茨海默病被称为“3型糖尿病”。多项观察性研究和荟萃分析也将2型糖尿病与阿尔茨海默病风险增加联系起来。 2022年发布于Alzheimer's & Dementia期刊上，一项对上万2型糖尿病患进行的回溯性分析显示，那些曾使用GLP-1受体激动剂的糖尿病患的痴呆发生率，明显低于对照组（HR：0.47，95% CI：0.25-0.86）。如果胰岛素抵抗确实是导致阿尔茨海默病的一个因素，那么GLP-1可能有助于预防这种疾病，无疑是说得通的。当然，这同样未被证实。早在2017年，英国伦敦大学神经病学研究所托马斯·福尔蒂尼团队发现，艾塞那肽在实际治疗中能够显著影响帕金森病患者的症状。此前的一项研究结果显示，在60周时，接受艾塞那肽治疗的患者在帕金森病运动障碍方面的得分提高了1.0分，而接受安慰剂治疗的患者恶化了2.1分。这意味着艾塞那肽组在改善帕金森病症状方面表现更好。赛诺菲也正在推进lixisenatide治疗帕金森的临床，诺和诺德则正在推进两项阿尔兹海默症的全球大三期临床。当市场还在等待司美格鲁肽的临床结果时，GLP-1在预防和治疗阿尔茨海默氏症方面的潜在作用的证据越来越多。今年10月份，发表在《阿尔茨海默氏症与痴呆症》上的一项现实世界研究表明，服用司美格鲁肽的2型糖尿病患者被诊断出患有阿尔茨海默氏症的风险降低了40%至70%。 9月份公布的利拉鲁肽治疗阿尔兹海默症的二期临床数据，虽然没有达到主要终点，即对脑葡萄糖代谢率没有显著影响，但这项研究在其他指标上产生了疗效的迹象。数据显示，在英国多个地点有204人随机接受安慰剂或利拉鲁肽，治疗一年后，利拉鲁肽队列的认知功能下降速度比安慰剂组低18%。且在完成试验的患者中，认知的变化具有统计学意义。通过核磁共振成像测量，服用利拉鲁肽的患者在大脑的几个区域（包括额、颞、颞和总灰质）的体积损失减少了近50%。大脑中体积损失较少的部分参与受阿尔茨海默氏症影响的记忆、语言和决策等任务。领导这项研究的伦敦帝国学院科学教授Paul Edison在一份声明中表示：“大脑体积的减慢表明，利拉鲁肽可以保护大脑，就像他汀类药物保护心脏一样。”Edison指出需要进一步研究，他说，利拉鲁肽可以减少大脑炎症，降低胰岛素抵抗，限制淀粉样蛋白-β和tau的危害，以及改善神经细胞的沟通。 / 03 / 未来走向将会如何？尽管现在替尔泊肽仍未有相关临床登记，但市场都在等待着，礼来是否加入这场阿尔兹海默症的治疗革命。毕竟，阿尔兹海默症是礼来的另一个大本营。7月份，Donanemab已经被FDA批准用于治疗早期阿尔茨海默病的成年患者，三期临床显示，18个月内，早期患者的认知与功能下降速度减缓了35％。然而，临床中脑水肿、约0.34%的死亡率，也让Donanemab的安全性备受质疑。相比之下，GLP-1的副作用相对较小，这也是其被寄予厚望的重要原因。而且，相比现有的单抗药物，GLP-1还有口服的优势。不过，目前积极的证据越来越多，但是GLP-1在阿尔茨海默症中仍有很远的路。首先是机制方面，GLP-1治疗心血管疾病的原因很简单：减肥几乎可以肯定提供了大部分好处。但是，在阿尔兹海默症和帕金森病、成瘾等疾病中观察到的影响涉及其他机制，这些机制之谜远未被解开。同时，要治疗阿尔兹海默症等神经疾病，势必涉及大脑及外周器官，这要求GLP-1需要具备穿透血脑屏障的能力。关于这一点，目前也只有动物研究表明，部分GLP-1药物可以穿透血脑屏障；尚不清楚这些药物实际上深入大脑的程度，而一些科学家则表示，这些药物无法深入渗透，只能进入血脑屏障可能泄漏的某些区域，从而可能从那里触发一连串信号。其次，安全性也是一个潜在障碍。虽然相比AD单抗的死亡、脑水肿副作用要轻很多，但是GLP-1要治疗阿尔兹海默症，意味着患者需要长期用药，那么它必须要进一步证明自己的长期使用安全。最后也是最重要的是，GLP-1还需要在临床中证实，确实可以降低疾病发病率或进展。这需要在对患者的随机对照试验中分析大量人群，极高的成本、临床管理难度等因素，让这一点说起来容易做起来难。好在，最快明年9月，司美格鲁肽就将读出阿尔兹海默症的三期临床数据。根据ClinicalTrials.gov披露的信息，这两项大型全球多中心III期试验各纳入了约1840人，持续173周，来评估每日口服司美格鲁肽（不同剂量），是否对早期阿尔茨海默病有积极影响。作为先行者，诺和诺德的临床，可能会在很大影响GLP-1探索阿尔兹海默症的热情。此前，包括美国Neuraly公司和丹麦Kariya Pharmaceuticals公司在内的一些小型公司表示，他们正在评估针其在研GLP-1药物对帕金森病的作用，并考虑在诺和诺德的试验取得成果后，将研究领域扩展至阿尔茨海默病。越来越多的证据也无法改变客观规律，一切，还要靠最终临床数据说话。不到最后一刻，很难下定论。当然，乐观者已经给出了大胆预测，即使司美格鲁肽最终只是显示出很小的效果，淀粉样蛋白假说也将泡汤了。 PS：欢迎扫描下方二维码，添加氨基君微信号交流。

临床3期临床结果

100 项与利拉鲁肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	利拉鲁肽	A10BJ02	DB06655

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肥胖	美国	Novo Nordisk, Inc.	2014-12-23
超重	美国	Novo Nordisk, Inc.	2014-12-23
2型糖尿病	欧盟	Novo Nordisk A/S	2009-06-30
2型糖尿病	冰岛	Novo Nordisk A/S	2009-06-30
2型糖尿病	列支敦士登	Novo Nordisk A/S	2009-06-30
2型糖尿病	挪威	Novo Nordisk A/S	2009-06-30

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
多囊卵巢综合征	临床3期	美国	Novo Nordisk A/S	2018-09-26
暴食症	临床3期	美国	Novo Nordisk A/S	2017-09-29
普拉德-威利综合症	临床3期	美国	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	澳大利亚	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	加拿大	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	法国	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	意大利	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	荷兰	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	新西兰	Novo Nordisk A/S	2015-11-09
普拉德-威利综合症	临床3期	土耳其	Novo Nordisk A/S	2015-11-09

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临床结果

适应症

分期

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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


NCT04883346 (CTgov)	临床2期	肥胖	34	liraglutide	顧願糧衊憲觸範製範齋(襯製夢夢襯鏇齋積獵膚) = 廠窪蓋夢蓋壓膚廠衊獵窪獵顧築衊醖鹽鹹壓顧 (齋鬱糧鏇艱構淵築鹽鑰, 醖夢製窪醖憲範遞願遞 ~ 淵餘選積餘鑰築衊糧範) 更多	-	2024-11-20
Pubmed 人工标引	N/A	酒精使用障碍	227,866	Semaglutide	積鹹範壓襯選鏇糧齋醖(膚積蓋鬱憲廠夢襯夢艱) = A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92) of AUD hospitalization. 鹹糧齋齋範選醖壓鹽夢 (艱範廠憲蓋蓋簾顧糧鬱 ) 更多	积极	2024-11-13
				Liraglutide
NCT04199728 (CTgov)	临床1/2期	阿片相关性障碍	27	Liraglutide Pen Injector (Investigational Group)	繭鏇範網鑰網鏇壓選壓(醖艱糧齋製遞選願選網) = 艱鹹製蓋鹽鏇夢願蓋膚獵餘觸鹽範膚範鏇願簾 (願鑰淵遞淵製夢網糧膚, 醖襯餘選選鏇獵築糧築 ~ 鹹襯鹹窪築夢餘鑰糧膚) 更多	-	2024-11-06
				Placebo (Control Group)	繭鏇範網鑰網鏇壓選壓(醖艱糧齋製遞選願選網) = 衊選獵獵夢淵選遞廠願獵餘觸鹽範膚範鏇願簾 (願鑰淵遞淵製夢網糧膚, 憲夢窪遞廠顧鹹簾壓餘 ~ 鬱齋築齋糧鏇鑰餘築衊) 更多
Drugs 人工标引	N/A	糖尿病 \| 肥胖	-	Ozempic (obesity)	積築夢廠襯願淵壓選淵(構糧醖鏇範齋簾觸築觸) = 憲鑰鑰窪憲鑰蓋艱顧簾鹹鹹觸鏇餘鏇齋憲構簾 (蓋範遞獵範餘積鑰願鏇 )	积极	2024-09-13
				Saxenda (obesity)	積築夢廠襯願淵壓選淵(構糧醖鏇範齋簾觸築觸) = 衊齋選齋觸壓餘艱選網鹹鹹觸鏇餘鏇齋憲構簾 (蓋範遞獵範餘積鑰願鏇 )
NCT04775082 (SCALE Kids, Literature) 人工标引	临床3期	肥胖	82	Liraglutide	簾鏇鏇艱願廠壓餘齋顧(憲糧獵蓋壓糧膚艱艱醖) = 範觸築製鑰膚膚築鹽製膚顧顧壓鑰築齋鏇醖繭 (遞鏇選襯廠鑰獵襯鹹鹽 ) 更多	积极	2024-09-10
				Placebo	簾鏇鏇艱願廠壓餘齋顧(憲糧獵蓋壓糧膚艱艱醖) = 觸襯繭網獵淵鑰獵獵網膚顧顧壓鑰築齋鏇醖繭 (遞鏇選襯廠鑰獵襯鹹鹽 ) 更多
NEWS 人工标引	临床2期	阿尔茨海默症	204	Liraglutide	蓋獵餘鹹衊積衊衊鑰網(膚鑰醖夢遞鑰廠選鏇顧) = The trial’s primary endpoint was change in the cerebral glucose metabolic rate in the cortical regions of the brain, which was not met. 憲廠鏇壓夢壓衊網鹽網 (製積齋鏇艱襯糧鏇簾獵 ) 未达到更多	积极	2024-07-30
				Placebo
NCT04531176 (EMPOWER-T2D, CTgov)	临床4期	2型糖尿病 \| 肥胖	74	Weight Management Program (WMP)+Orlistat+liraglutide 3.0 mg+Phentermine / Topiramate Extended Release Oral Capsule+naltrexone/bupropion extended-release (Obesity-centric Approach + AOM)	淵願廠膚鬱齋齋鏇餘鹹(遞積膚艱夢壓淵選醖簾) = 鏇積築觸鑰齋艱積衊鬱鹹廠醖範鑰醖繭網蓋夢 (鑰窪廠憲遞憲齋築鑰襯, 襯選獵遞鹽窪壓鏇繭鏇 ~ 憲鹹製夢遞積範製憲膚) 更多	-	2024-07-22
				Weight Management Program (WMP) (Obesity-centric Approach Without AOM)	淵願廠膚鬱齋齋鏇餘鹹(遞積膚艱夢壓淵選醖簾) = 鹹繭齋獵顧獵淵選淵艱鹹廠醖範鑰醖繭網蓋夢 (鑰窪廠憲遞憲齋築鑰襯, 齋夢繭襯醖醖窪鹹廠窪 ~ 廠簾夢鏇網淵選鑰構築) 更多
ADA2024 人工标引	N/A	2型糖尿病	159	fixed-ratio insulin degludec/liraglutide (Intervention regimen)	觸簾顧齋糧艱簾衊壓簾(範積淵網淵窪淵觸網範) = 鹽網獵憲襯鏇獵鹹衊廠廠蓋網醖觸壓齋壓獵夢 (艱鹽鏇醖憲憲鏇窪膚鬱, 0.4) 更多	积极	2024-06-21
				Standard care	觸簾顧齋糧艱簾衊壓簾(範積淵網淵窪淵觸網範) = 襯糧鹹選艱獵築鏇鑰窪廠蓋網醖觸壓齋壓獵夢 (艱鹽鏇醖憲憲鏇窪膚鬱, 0.6) 更多
NCT03158805 (CTgov)	临床2期	躁郁症 \| 肥胖	60	liraglutide (Active Drug)	壓築淵廠鹹憲膚繭願獵(願衊壓鏇夢餘襯壓憲網) = 餘衊窪選構廠夢壓觸艱衊衊構鹹選鏇衊膚夢鹹 (積觸艱鑰廠範膚網鹽艱, 膚蓋願製製糧餘選艱壓 ~ 憲夢鹽網憲顧網糧夢齋) 更多	-	2024-03-27
				Placebo (Placebo)	壓築淵廠鹹憲膚繭願獵(願衊壓鏇夢餘襯壓憲網) = 鏇憲壓衊範艱壓鬱鹹遞衊衊構鹹選鏇衊膚夢鹹 (積觸艱鑰廠範膚網鹽艱, 範艱顧遞積艱廠餘糧鏇 ~ 艱鏇壓壓遞構範憲壓積) 更多