GLP-1 RA应用于2型糖尿病合并脑卒中的研究进展

摘要/Abstract

摘要： 脑卒中具有高发病率、高致残率、高死亡率的特点，脑卒中与糖尿病息息相关，二者常伴随发生。近年来发现胰高血糖素样肽-1受体激动剂（GLP-1 receptor agonists，GLP-1 RA）应用于2型糖尿病合并脑卒中的患者可以有效改善其脑血管结局，提示GLP-1 RA在脑卒中的预防和治疗领域存在应用潜力。多项研究表明，GLP-1 RA可以通过降低脑卒中危险因素、保护脑组织、改善认知等机制来发挥其防治作用。本文就GLP-1 RA应用于脑卒中的机制进行综述，并从不良反应的视角探讨合理用药及防治措施。

关键词: font-size:medium, ">胰高血糖素样肽-1受体激动剂；脑卒中；糖尿病；不良反应

Abstract: Stroke is characterized by high morbidity， high disability and high mortality. Stroke is closely related to diabetes， and both of them often happen together. In recent years， it has been found that GLP-1 receptor agonist (GLP-1 RA) can effectively improve the cerebrovascular outcome of patients with type 2 diabetes mellitus complicated with stroke， suggesting that GLP-1 RA has potential application in the field of prevention and treatment of stroke. Many studies have shown that GLP-1ＲA can play its preventive and therapeutic role by reducing the risk factors of stroke， protecting brain tissue and improving cognition. This article reviews the mechanism of GLP-1 RA applied to stroke， and discusses the rational drug use and prevention measures from the perspective of adverse reactions.

Key words: font-size:medium, ">Glucagon-like peptide-1 receptor agonist； Stroke； Diabetes mellitus； Adverse effect

中图分类号:

鞠惠, 王湘云, 牟静, 吴淑敏, 葛磊. GLP-1 RA应用于2型糖尿病合并脑卒中的研究进展[J]. 中国药物评价, 2023, 40(4): 349-352.

JU Hui, WANG Xiang-yun, MU Jing, WU Shu-min, GE Lei . Research Progress and Adverse Reactions of GLP-1 RA Applied to Stroke[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2023, 40(4): 349-352.

参考文献

[1] 葛均波，霍勇，高秀芳，等.改善心血管和肾脏结局的新型抗高血糖药物临床应用中国专家建议[J]. 中华高血压杂志， 2020， 28(3)：225-233.
     [2] Vergès B， Aboyans V， Angoulvant D， et al. Protection against stroke with glucagon-like peptide-1 receptor agonists： a comprehensive review of potential mechanisms[J]. Cardiovasc Diabetol， 2022， 21(1)：242.
     [3] 崔艳敏，宋岳涵.DDP-4抑制剂与GLP-1受体激动剂治疗2型糖尿病患者的有效性研究[J]. 河北医药， 2022， 44(2)：210-213.
     [4] Goldenberg RM， Cheng AYY， Fitzpatrick T， et al. Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes： A Call to Action for Neurologists[J]. Stroke， 2022， 53(5)：1813-1822.
     [5] 王陇德，彭斌，张鸿祺，等.《中国脑卒中防治报告2020》概要[J]. 中国脑血管病杂志， 2022， 19(2)：136-144.
     [6] 《中国脑卒中防治报告2019》概要[J]. 中国脑血管病杂志， 2020， 17(5)：272-281.
     [7] Patel V， Joharapurkar A， Kshirsagar S， et al. Central administration of coagonist of GLP-1 and glucagon receptors improves dyslipidemia[J]. Biomed Pharmacother， 2018， 98：364-371.
     [8] Goud A， Zhong J， Peters M， et al. GLP-1 Agonists and Blood Pressure： A Review of the Evidence[J]. Curr Hypertens Rep， 2016， 18(2)：16.
     [9] Saraiva JFK， Franco D. Oral GLP-1 analogue： perspectives and impact on atherosclerosis in type 2 diabetic patients[J]. Cardiovasc Diabetol， 2021， 20(1)：235.
     [10] Cameron-Vendrig A， Reheman A， Siraj MA， et al. Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis[J]. Diabetes， 2016， 65(6)：1714-1723.
     [11] Nizari S， Basalay M， Chapman P， et al. Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles， increases cerebral blood flow， and mediates remote (pre)conditioning neuroprotection against ischaemic stroke[J]. Basic Res Cardiol， 2021， 116(1)：32.
     [12] Basalay MV， Davidson SM， Yellon DM. Neuroprotection in Rats Following Ischaemia-Reperfusion Injury by GLP-1 Analogues-Liraglutide and Semaglutide[J]. Cardiovasc Drugs Ther， 2019， 33(6)：661-667.
     [13] Rocha-Ferreira E， Poupon L， Zelco A， et al. Neuroprotective exendin-4 enhances hypothermia therapy in a model of hypoxic-ischaemic encephalopathy[J]. Brain， 2018， 141(10)：2925-2942.
     [14] 杜月. GLP-1受体激动剂艾塞那肽对大鼠脑缺血再灌注模型炎症反应的影响[D]. 山东第一医科大学， 2019.
     [15] 范伟超，曾庆，张卓栋，等.虚拟现实技术在脑卒中后认知功能障碍康复中的研究进展[J]. 中国康复， 2022， 37(12)：760-764.
     [16] Day SM， Yang W， Ewin S， et al. Glucagon-like peptide-1 cleavage product GLP-1 (9-36) amide enhances hippocampal long-term synaptic plasticity in correlation with suppression of Kv4.2 expression and eEF2 phosphorylation[J]. Hippocampus， 2017， 27(12)：1264-1274.
     [17] 张鑫芳. 新型降糖药物GLP-1受体激动剂的认知改善作用[D]. 兰州大学， 2022.
     [18] Taylor SR， Moody MT. Acute Kidney Injury Occurring in a Patient Initiated on Dulaglutide[J]. J Pharm Technol， 2018， 34(5)：231-232.
     [19] Parvataneni S， Ramachandran R， Then E， et al. An Exceedingly Rare Case of Liraglutide-Induced Liver Injury[J]. Case Rep Gastrointest Med， 2021， 2021：6306149.
     [20] Steinberg WM， Buse JB， Ghorbani MLM， et al. Amylase， Lipase， and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide： Results From the LEADER Randomized Trial[J]. Diabetes Care， 2017， 40(7)：966-972.
     [21] Li Y， Li L， De Peng Y， et al. Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients： A Subgroup Analysis of a Randomized Trial (AWARD-CHN2)[J]. Diabetes Ther， 2019， 10(4)：1435-1452.
     [22] Egan AG， Blind E， Dunder K， et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment[J]. N Engl J Med， 2014， 370(9)：794-797.
     [23] Iqbal AM， Imamudeen N， Basheer A， et al. Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues[J]. Curr Drug Saf， 2021， 16(2)：197-206.
     [24] Fukuda G， Yoshida T， Hirayama A， et al. Dulaglutide-related bullous pemphigoid in a patient with type?2 diabetes： A case report[J]. Geriatr Gerontol Int， 2019， 19(12)：1289-1290.
     [25] Kyriakos G， Diamantis E， Memi E， et al. An Uncommon Case of Dulaglutide-Related Morbilliform Drug Eruption[J]. Cureus， 2022， 14(1)：e21536.
     [26] Liu X， Zhai A， Zhang B. A case report of severe adverse reaction of exenatide： Anaphylactic shock. Medicine (Baltimore)[J]. 2022， 101(39)：e30805.
     [27] Handelsman Y， Wyne K， Cannon A， et al. Glycemic Efficacy， Weight Effects， and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists[J]. J Manag Care Spec Pharm， 2018， 24(9-a Suppl)：S14-29.
     [28] Okiro JO， Mc Hugh C， Abdalla A. Is it safe to acutely discontinue insulin therapy in patients with chronic hyperglycaemia starting GLP-1R agonists? [J]. BMJ Case Rep， 2017， 2017：bcr2017220437.