AccScience Publishing / AN / Online First / DOI: 10.36922/AN025150027
Submit to AN
Cite this article
9
Download
175
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

Glucagon-like peptide-1 receptor agonists as potential preventive and therapeutic agents in ischemic stroke

Muhammad Ali1 ,  Meng Yang1 ,  Sarah Eide1 ,  Hong-Shuo Sun1,2,3 ,  Tianru Jin1,4 ,  Zhong-Ping Feng1*
Show Less
1 Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2 Department of Surgery, Division of Anatomy, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
3 Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Ontario, Canada
4 Banting and Best Diabetes Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Advanced Neurology, 025150027 https://doi.org/10.36922/AN025150027
Received: 7 April 2025 | Revised: 13 July 2025 | Accepted: 22 July 2025 | Published online: 11 September 2025
(This article belongs to the Special Issue Advanced Neurology 3rd Anniversary Special Issue)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
XML
Cite
Abstract

Stroke remains a significant contributor to mortality and morbidity worldwide, imposing a significant socioeconomic burden and underscoring the urgent need for both preventative and therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for the treatment of metabolic disorders, have demonstrated promising neuroprotective properties through multiple mechanisms, including anti-inflammatory and antioxidation effects, as well as preservation of the blood–brain barrier. GLP-1RAs reduce the occurrence and severity of ischemic stroke by alleviating metabolic disorders that contribute to cerebrovascular disease. This review discusses the role of GLP-1RAs in ischemic stroke, focusing on their direct neuroprotective properties and indirect benefits through the modulation of metabolic risk factors, including metabolic syndrome and its components. By highlighting the therapeutic potential of GLP-1RAs, we demonstrate their value as both a preventative and therapeutic strategy against ischemic stroke.

Graphical abstract
Keywords
Glucagon-like peptide-1
Ischemic stroke
Neuroprotection
Neuroinflammation
Blood–brain barrier
Oxidative stress
Obesity
Metabolic disorders
Funding
This work was supported by a Canadian Institutes of Health Research Project Grant (CIHR PJT-191824) to ZPF. MA received a CIHR Canada Graduate Scholarship (CGS-M) and MY and SE received Ontario Graduate Scholarships (Doctoral).
Conflict of interest
Hong-Shuo Sun and Zhong-Ping Feng are Editorial Board Members of this journal, but were not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. The Top 10 Causes of Death. 2024. Available from: https:// www.who.int/news-room/fact-sheets/detail/the-top-10- causes-of-death [Last accessed on 2024 Sep 22].

 

  1. Sun HS. Current mechanisms in stroke. Acta Pharmacol Sin. 2013;34(1):1-2. doi: 10.1038/aps.2012.174

 

  1. Boehme AK, Esenwa C, Elkind MSV. Stroke risk factors, genetics, and prevention. Circ Res. 2017;120(3):472-495. doi: 10.1161/CIRCRESAHA.116.308398

 

  1. Pu L, Wang L, Zhang R, Zhao T, Jiang Y, Han L. Projected global trends in ischemic stroke incidence, deaths and disability-adjusted life years from 2020 to 2030. Stroke. 2023;54(5):1330-1339. doi: 10.1161/STROKEAHA.122.040073

 

  1. Hurd MD, Goel I, Sakai Y, Teramura Y. Current status of ischemic stroke treatment: From thrombolysis to potential regenerative medicine. Regen Ther. 2021;18:408-417. doi: 10.1016/j.reth.2021.09.009

 

  1. Dhawan J, Benveniste H, Luo Z, Nawrocky M, Smith SD, Biegon A. A new look at glutamate and ischemia: NMDA agonist improves long-term functional outcome in a rat model of stroke. Future Neurol. 2011;6(6):823-834. doi: 10.2217/fnl.11.55

 

  1. Drucker DJ. The benefits of GLP-1 drugs beyond obesity. Science. 2024;385(6706):258-260. doi: 10.1126/science.adn4128

 

  1. Abd El-Rady NM, Ahmed A, Abdel-Rady MM, Ismail OI. Glucagon-like peptide-1 analog improves neuronal and behavioral impairment and promotes neuroprotection in a rat model of aluminum-induced dementia. Physiol Rep. 2021;8(24):e14651. doi: 10.14814/phy2.14651

 

  1. Collins L, Costello RA. Glucagon-Like peptide-1 receptor agonists. In: StatPearls. Treasure Island, (FL): StatPearls Publishing; 2024. Available from: http://www.ncbi.nlm.nih. gov/books/NBK551568 [Last accessed on 2024 Oct 31].

 

  1. Kuhre RE, Deacon CF, Holst JJ, Petersen N. What is an L-cell and how do we study the secretory mechanisms of the L-cell? Front Endocrinol. 2021;12:694284. doi: 10.3389/fendo.2021.694284

 

  1. Drucker DJ. Discovery of GLP-1-based drugs for the treatment of obesity. N Engl J Med. 2025;392:612-615. doi: 10.1056/NEJMcibr2409089

 

  1. Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol. 2012;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x

 

  1. Zheng Z, Zong Y, Ma Y, et al. Glucagon-like peptide-1 receptor: Mechanisms and advances in therapy. Signal Transduct Target Ther. 2024;9(1):234. doi: 10.1038/s41392-024-01931-z

 

  1. Rowlands J, Heng J, Newsholme P, Carlessi R. Pleiotropic effects of GLP-1 and analogs on cell signaling, metabolism, and function. Front Endocrinol. 2018;9:672. doi: 10.3389/fendo.2018.00672

 

  1. Muscogiuri G, DeFronzo RA, Gastaldelli A, Holst JJ. Glucagon-like peptide-1 and the central/peripheral nervous system: Crosstalk in diabetes. Trends Endocrinol Metab. 2017;28(2):88-103. doi: 10.1016/j.tem.2016.10.001

 

  1. Cabou C, Burcelin R. GLP-1, the gut-brain, and brain-periphery axes. Rev Diabet Stud. 2011;8(3):418. doi: 10.1900/RDS.2011.8.418

 

  1. Tian L, Jin T. The incretin hormone GLP-1 and mechanisms underlying its secretion. J Diabetes. 2016;8(6):753-765. doi: 10.1111/1753-0407.12439

 

  1. Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72-130. doi: 10.1016/j.molmet.2019.09.010

 

  1. Lee S, Lee DY. Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. Ann Pediatr Endocrinol Metab. 2017;22(1):15-26. doi: 10.6065/apem.2017.22.1.15

 

  1. Doyle ME, Theodorakis MJ, Holloway HW, Bernier M, Greig NH, Egan JM. The importance of the nine-amino acid C-terminal sequence of exendin-4 for binding to the GLP-1 receptor and for biological activity. Regul Pept. 2003;114(2-3):153-158. doi: 10.1016/S0167-0115(03)00120-4

 

  1. Jacobsen LV, Flint A, Olsen AK, Ingwersen SH. Liraglutide in type 2 diabetes mellitus: Clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2016;55:657-672. doi: 10.1007/s40262-015-0343-6

 

  1. Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne). 2019;10:155. doi: 10.3389/fendo.2019.00155

 

  1. Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as a diabetes therapeutic. Curr Diabetes Rev. 2013;9(2):161-193. doi: 10.2174/1573399811309020007

 

  1. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi: 10.1056/NEJMoa2206038

 

  1. Nicholls SJ, Tofé S, le Roux CW, et al. Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: A Post hoc analysis from the SURPASS clinical trial program. Cardiovasc Diabetol. 2024;23(1):63. doi: 10.1186/s12933-024-02147-9

 

  1. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. doi: 10.1056/NEJMoa2107519

 

  1. Aronne LJ, Horn DB, Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26-36. doi: 10.1056/NEJMoa2416394

 

  1. Willard FS, Douros JD, Gabe MBN, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17):e140532. doi: 10.1172/jci.insight.140532

 

  1. McIntosh CH, Widenmaier S, Kim S. Glucose‐dependent insulinotropic polypeptide signaling in pancreatic β‐cells and adipocytes. J Diabetes Investig. 2012;3(2):96-106. doi: 10.1111/j.2040-1124.2012.00196.x

 

  1. Karlsson M, Zhang C, Méar L, et al. A single-cell type transcriptomics map of human tissues. Sci Adv. 2021;7(31):eabh2169. doi: 10.1126/sciadv.abh2169

 

  1. Zhu H, Zhang Y, Shi Z, et al. The neuroprotection of liraglutide against ischaemia-induced apoptosis through the activation of the PI3K/AKT and MAPK pathways. Sci Rep. 2016;6(1):26859. doi: 10.1038/srep26859

 

  1. Li PC, Liu LF, Jou MJ, Wang HK. The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice. BMC Neurosci. 2016;17(1):37. doi: 10.1186/s12868-016-0272-9

 

  1. Hölscher C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer’s and Parkinson’s disease models. Neuropharmacology. 2018;136(Pt B):251-259. doi: 10.1016/j.neuropharm.2018.01.040

 

  1. Salcedo I, Tweedie D, Li Y, Greig NH. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: An emerging opportunity to treat neurodegenerative and cerebrovascular disorders. Br J Pharmacol. 2012;166(5):1586-1599. doi: 10.1111/j.1476-5381.2012.01971.x

 

  1. McClean P, Jalewa J, Holscher C. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behav Brain Res. 2015;293:96-106. doi: 10.1016/j.bbr.2015.07.024

 

  1. 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. Basic Res Cardiol. 2021;116(1):32. doi: 10.1007/s00395-021-00873-9

 

  1. Darsalia V, Hua S, Larsson M, et al. Exendin-4 reduces ischemic brain injury in normal and aged type 2 diabetic mice and promotes microglial M2 polarization. PLoS One. 2014;9(8):e103114. doi: 10.1371/journal.pone.0103114

 

  1. Bailey J, Coucha M, Bolduc DR, et al. GLP-1 receptor nitration contributes to loss of brain pericyte function in a mouse model of diabetes. Diabetologia. 2022;65(9):1541-1554. doi: 10.1007/s00125-022-05730-5

 

  1. De Luca L, Bilato C, Navazio A, et al. ANMCO statement: Semaglutide in the cardio-nephro-metabolic continuum. Eur Heart J Suppl. 2025;27(Supplement_5):v247-v255. doi: 10.1093/eurheartjsupp/suaf071

 

  1. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392(5):427-437. doi: 10.1056/NEJMoa2410027

 

  1. Li W, Qiu X, Ma H, Geng Q. Incidence and long-term specific mortality trends of metabolic syndrome in the United States. Front Endocrinol (Lausanne). 2023;13:1029736. doi: 10.3389/fendo.2022.1029736

 

  1. Drucker DJ. Efficacy and safety of GLP-1 medicines for type 2 diabetes and obesity. Diabetes Care. 2024;47(11):1873-1888. doi: 10.2337/dci24-0003

 

  1. Kosiborod MN, Bhatta M, Davies M, et al. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023;25(2):468-478. doi: 10.1111/dom.14890

 

  1. Della Pepa G, Patrício BG, Carli F, et al. GLP-1 receptor agonist treatment improves fasting and postprandial lipidomic profiles independently of diabetes and weight loss. Diabetes. 2024;73(10):1605-1614. doi: 10.2337/db23-0972

 

  1. Horn JW, Feng T, Mørkedal B, et al. Body mass index measured repeatedly over 42 years as a risk factor for ischemic stroke: The HUNT study. Nutrients. 2023;15(5):1232. doi: 10.3390/nu15051232

 

  1. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi: 10.1056/NEJMoa2032183

 

  1. Ryan DH, Lingvay I, Deanfield J, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024;30(7):2049-2057. doi: 10.1038/s41591-024-02996-7

 

  1. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 randomized clinical trial. JAMA. 2022;327(2):138-150. doi: 10.1001/jama.2021.23619

 

  1. Zhang P, Liu Y, Ren Y, Bai J, Zhang G, Cui Y. The efficacy and safety of liraglutide in the obese, non-diabetic individuals: A systematic review and meta-analysis. Afr Health Sci. 2019;19(3):2591-2599. doi: 10.4314/ahs.v19i3.35

 

  1. Chen H, Simar D, Pegg K, Saad S, Palmer C, Morris MJ. Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents. Diabetologia. 2014;57(3):614-622. doi: 10.1007/s00125-013-3132-5

 

  1. Chen R, Ovbiagele B, Feng W. Diabetes and stroke: Epidemiology, pathophysiology, pharmaceuticals and outcomes. Am J Med Sci. 2016;351(4):380-386. doi: 10.1016/j.amjms.2016.01.011

 

  1. Lau LH, Lew J, Borschmann K, Thijs V, Ekinci EI. Prevalence of diabetes and its effects on stroke outcomes: A meta‐analysis and literature review. J Diabetes Investig. 2018;10(3):780-792. doi: 10.1111/jdi.12932

 

  1. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28(5):1092-1100. doi: 10.2337/diacare.28.5.1092

 

  1. Gu J, Meng X, Guo Y, et al. The efficacy and safety of liraglutide added to metformin in patients with diabetes: A meta-analysis of randomized controlled trials. Sci Rep. 2016;6(1):32714. doi: 10.1038/srep32714

 

  1. Ferrari F, Moretti A, Villa RF. Hyperglycemia in acute ischemic stroke: Physiopathological and therapeutic complexity. Neural Regen Res. 2021;17(2):292-299 doi: 10.4103/1673-5374.317959

 

  1. Yaribeygi H, Farrokhi FR, Abdalla MA, et al. The effects of glucagon-like peptide-1 receptor agonists and dipeptydilpeptidase-4 inhibitors on blood pressure and cardiovascular complications in diabetes. J Diabetes Res. 2021;2021:6518221. doi: 10.1155/2021/6518221

 

  1. Yao H, Zhang A, Li D, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: Systematic review and network meta-analysis. BMJ. 2024;384:e076410. doi: 10.1136/bmj-2023-076410

 

  1. Wei J, Yang B, Wang R, et al. Risk of stroke and retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: An eight RCTs meta-analysis. Front Endocrinol (Lausanne). 2022;13:1007980. doi: 10.3389/fendo.2022.1007980

 

  1. Stefanou MI, Theodorou A, Malhotra K, et al. Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis. Eur Stroke J. 2024;9(3):530-539. doi: 10.1177/23969873241234238

 

  1. Fontanella RA, Ghosh P, Pesapane A, et al. Tirzepatide prevents neurodegeneration through multiple molecular pathways. J Transl Med. 2024;22:114. doi: 10.1186/s12967-024-04927-z

 

  1. Yang YS, Chen HH, Huang CN, Hsu CY, Hu KC, Kao CH. GLP-1RAs for ischemic stroke prevention in patients with type 2 diabetes without established atherosclerotic cardiovascular disease. Diabetes Care. 2022;45(5):1184-1192. doi: 10.2337/dc21-1993

 

  1. Strain WD, Frenkel O, James MA, et al. Effects of semaglutide on stroke subtypes in type 2 diabetes: Post hoc analysis of the randomized SUSTAIN 6 and PIONEER 6. Stroke. 2022;53(9):2749-2757. doi: 10.1161/STROKEAHA.121.037775

 

  1. Verma S, Poulter NR, Bhatt DL, et al. Effects of liraglutide on cardiovascular outcomes in patients with type 2 diabetes mellitus with or without history of myocardial infarction or stroke. Circulation. 2018;138(25):2884-2894. doi: 10.1161/CIRCULATIONAHA.118.034516

 

  1. Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025;31(3):951-962. doi: 10.1038/s41591-024-03412-w

 

  1. Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: A review of their efficacy and tolerability Diabetes Care. 2011;34(Suppl 2):S279-S284. doi: 10.2337/dc11-s231

 

  1. Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse effects of GLP-1 receptor agonists. Rev Diabet Stud. 2014;11(3):202-230. doi: 10.1900/RDS.2014.11.202

 

  1. Rivera FB, Cruz LLA, Magalong JV, et al. Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials. Am J Prev Cardiol. 2024;18:100679. doi: 10.1016/j.ajpc.2024.100679

 

  1. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA. 2023;330(18):1795-1797. doi: 10.1001/jama.2023.19574

 

  1. Ayoub M, Chela H, Amin N, et al. Pancreatitis risk associated with GLP-1 receptor agonists, considered as a single class, in a comorbidity-free subgroup of type 2 diabetes patients in the United States: A propensity score-matched analysis. J Clin Med. 2025;14(3):944. doi: 10.3390/jcm14030944

 

  1. Wookey O, Galligan A, Wilkie B, MacIsaac A, Paratz E. Perioperative use of GLP-1 receptor agonists in patients undergoing cardiac procedures: A scoping review. Heart Lung Circ. 2025;34(2):105-117. doi: 10.1016/j.hlc.2024.11.025

 

  1. American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists. Available from: https://www.asahq.org/ about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative [Last accessed on 2025 Jul 09].

 

  1. Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771. doi: 10.1136/bmj.d7771

 

  1. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: A review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2015;6(1):19-28. doi: 10.1177/2042018814559725

 

  1. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-1844. doi: 10.1056/NEJMoa1607141

 

  1. Husain M, Bain SC, Jeppesen OK, et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020;22(3):442-451. doi: 10.1111/dom.13955

 

  1. Berg S, Stickle H, Rose SJ, Nemec EC. Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis. Obes Rev. 2025;26(8):e13929. doi: 10.1111/obr.13929

 

  1. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi: 10.1111/dom.14725

 

  1. U.S. Food and Drug Administration. FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight. FDA; 2024. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or [Last accessed on 2025 Jul 07].

 

  1. U.S. Food and Drug Administration. FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. FDA; 2025. Available from: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss [Last accessed on 2025 Jul 07].

 

  1. Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: A meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2025;13(1):15-28. doi: 10.1016/S2213-8587(24)00271-7

 

  1. Iqbal J, Wu HX, Hu N, et al. Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus-a systematic review and meta-analysis of randomized control trials. Obes Rev. 2022;23(6):e13435. doi: 10.1111/obr.13435

 

  1. Ding M, Fang QH, Cui YT, et al. Liraglutide prevents β-cell apoptosis via inactivation of NOX2 and its related signaling pathway. J Diabetes Complications. 2019;33(4):267-277. doi: 10.1016/j.jdiacomp.2018.12.013

 

  1. Kapodistria K, Tsilibary E, Kotsopoulou E, Moustardas P, Kitsiou P. Liraglutide, a human glucagon‐like peptide‐1 analogue, stimulates AKT‐dependent survival signalling and inhibits pancreatic β‐cell apoptosis. J Cell Mol Med. 2018;22(6):2970-2980. doi: 10.1111/jcmm.13259

 

  1. Fernández-Millán E, Martín MA, Goya L, et al. Glucagon-like peptide-1 improves beta-cell antioxidant capacity via extracellular regulated kinases pathway and Nrf2 translocation. Free Radic Biol Med. 2016;95:16-26. doi: 10.1016/j.freeradbiomed.2016.03.002

 

  1. Lee YS, Lee C, Choung JS, Jung HS, Jun HS. Glucagon-like peptide 1 increases β-cell regeneration by promoting α- to β-cell transdifferentiation. Diabetes. 2018;67(12):2601-2614. doi: 10.2337/db18-0155

 

  1. Wei R, Gu L, Yang J, et al. Antagonistic glucagon receptor antibody promotes α-Cell proliferation and increases β-cell mass in diabetic mice. iScience. 2019;16:326-339. doi: 10.1016/j.isci.2019.05.030

 

  1. Wu YR, Shi XY, Ma CY, Zhang Y, Xu RX, Li JJ. Liraglutide improves lipid metabolism by enhancing cholesterol efflux associated with ABCA1 and ERK1/2 pathway. Cardiovasc Diabetol. 2019;18:146. doi: 10.1186/s12933-019-0954-6

 

  1. Beiroa D, Imbernon M, Gallego R, et al. GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK. Diabetes. 2014;63(10):3346-3358. doi: 10.2337/db14-0302

 

  1. Xu F, Lin B, Zheng X, et al. GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1. Diabetologia. 2016;59(5):1059-1069. doi: 10.1007/s00125-016-3896-5

 

  1. Han F, Hou N, Liu Y, et al. Liraglutide improves vascular dysfunction by regulating a cAMP-independent PKA-AMPK pathway in perivascular adipose tissue in obese mice. Biomed Pharmacother. 2019;120:109537. doi: 10.1016/j.biopha.2019.109537

 

  1. Chen L, Xu H, Zhang C, He J, Wang Y. Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway. Am J Transl Res. 2024;16(4):1102-1117. doi: 10.62347/IZGJ1332

 

  1. Lyu X, Yan K, Wang X, et al. A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice. Endocr J. 2022;69(10):1233-1244. doi: 10.1507/endocrj.EJ21-0802

 

  1. Gutierrez AD, Gao Z, Hamidi V, et al. Anti-diabetic effects of GLP1 analogs are mediated by thermogenic interleukin-6 signaling in adipocytes. Cell Rep Med. 2022;3(11):100813. doi: 10.1016/j.xcrm.2022.100813

 

  1. Kaihara KA, Dickson LM, Ellenbroek JH, Orr CMD, Layden BT, Wicksteed B. PKA enhances the acute insulin response leading to the restoration of glucose control. Diabetes. 2014;64(5):1688-1697. doi: 10.2337/db14-1051

 

  1. Gupta T, Kaur M, Shekhawat D, Aggarwal R, Nanda N, Sahni D. Investigating the glucagon-like peptide-1 and its receptor in human brain: Distribution of expression, functional implications, age-related changes and species specific characteristics. Basic Clin Neurosci. 2023;14(3):341-353. doi: 10.32598/bcn.2021.2554.2

 

  1. Li Y, Perry T, Kindy MS, et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci U S A. 2009;106(4):1285-1290. doi: 10.1073/pnas.0806720106

 

  1. Qian Z, Chen H, Xia M, et al. Activation of glucagon-like peptide-1 receptor in microglia attenuates neuroinflammation-induced glial scarring via rescuing Arf and Rho GAP adapter protein 3 expressions after nerve injury. Int J Biol Sci. 2022;18(4):1328-1346. doi: 10.7150/ijbs.68974

 

  1. Jing F, Zou Q, Wang Y, Cai Z, Tang Y. Activation of microglial GLP-1R in the trigeminal nucleus caudalis suppresses central sensitization of chronic migraine after recurrent nitroglycerin stimulation. J Headache Pain. 2021;22(1):86. doi: 10.1186/s10194-021-01302-x

 

  1. Noguchi T, Katoh H, Nomura S, Okada K, Watanabe M. The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype. Front Neurosci. 2024;18:1342944. doi: 10.3389/fnins.2024.1342944

 

  1. Gong N, Xiao Q, Zhu B, et al. Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity. J Neurosci. 2014;34(15):5322-5334. doi: 10.1523/JNEUROSCI.4703-13.2014

 

  1. Gad SN, Nofal S, Raafat EM, Ahmed AAE. Lixisenatide reduced damage in hippocampus CA1 Neurons in a rat model of cerebral ischemia-reperfusion possibly via the ERK/P38 signaling pathway. J Mol Neurosci. 2020;70(7):1026-1037. doi: 10.1007/s12031-020-01497-9

 

  1. Yang S, Zhao X, Zhang Y, et al. Tirzepatide shows neuroprotective effects via regulating brain glucose metabolism in APP/PS1 mice. Peptides. 2024;179:171271. doi: 10.1016/j.peptides.2024.171271

 

  1. Teramoto S, Miyamoto N, Yatomi K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2011;31(8):1696-1705. doi: 10.1038/jcbfm.2011.51

 

  1. Kim S, Jeong J, Jung HS, et al. Anti-inflammatory effect of glucagon like peptide-1 receptor agonist, exendin-4, through modulation of IB1/JIP1 expression and JNK signaling in stroke. Exp Neurobiol. 2017;26(4):227-239. doi: 10.5607/en.2017.26.4.227

 

  1. Sadek MA, Kandil EA, El Sayed NS, Sayed HM, Rabie MA. Semaglutide, a novel glucagon-like peptide-1 agonist, amends experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice: Involvement of the PI3K/Akt/GSK-3β pathway. Int Immunopharmacol. 2023;115:109647. doi: 10.1016/j.intimp.2022.109647

 

  1. Yang JL, Chen WY, Chen YP, Kuo CY, Chen SD. Activation of GLP-1 receptor enhances neuronal base excision repair via PI3K-AKT-induced expression of apurinic/apyrimidinic endonuclease 1. Theranostics. 2016;6(12):2015-2027. doi: 10.7150/thno.15993

 

  1. Shan Y, Tan S, Lin Y, et al. The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke. J Neuroinflammation. 2019;16(1):242. doi: 10.1186/s12974-019-1638-6

 

  1. Tu XK, Chen PP, Chen JY, Ding YH, Chen Q, Shi SS. GLP-1R knockdown abrogates the protective effects of liraglutide on ischaemic stroke via inhibition of M2 polarisation and activation of NLRP3 inflammasome by reducing Nrf2 activation. Neuropharmacology. 2023;237:109603. doi: 10.1016/j.neuropharm.2023.109603

 

  1. Abdel-latif RG, Heeba GH, Taye A, Khalifa MMA. Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(7):705-717. doi: 10.1007/s00210-018-1497-1

 

  1. Lu HY, Li SY, Yang JL. The role of GLP-1 affects fate of astrocytes following ischemic stroke in mice. Physiology. 2024;39(S1):508. doi: 10.1152/physiol.2024.39.S1.508

 

  1. Zhang Q, Liu C, Shi R, et al. Blocking C3d+/GFAP+ A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after ischemic stroke. Aging Dis. 2022;13(3):943-959. doi: 10.14336/AD.2021.1029

 

  1. Kuroki T, Tanaka R, Shimada Y, et al. Exendin-4 inhibits matrix metalloproteinase-9 activation and reduces infarct growth after focal cerebral ischemia in hyperglycemic mice. Stroke. 2016;47(5):1328-1335. doi: 10.1161/STROKEAHA.116.012934

 

  1. Chen Y, Zhang X, He J, Xie Y, Yang Y. Delayed administration of the glucagon-like peptide 1 analog liraglutide promoting angiogenesis after focal cerebral ischemia in mice. J Stroke Cerebrovasc Dis. 2018;27(5):1318-1325. doi: 10.1016/j.jstrokecerebrovasdis.2017.12.015

 

  1. Luna-Marco C, de Marañon AM, Hermo-Argibay A, et al. Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. Redox Biol. 2023;66:102849. doi: 10.1016/j.redox.2023.102849

 

  1. Verma S, Husain M, Madsen CM, et al. Neutrophil to lymphocyte ratio predicts cardiovascular events in people with type 2 diabetes: Post hoc analysis of the SUSTAIN 6 and PIONEER 6 cardiovascular outcomes trials. Diabetes Obes Metab. 2023;25(8):2398-2401. doi: 10.1111/dom.15088

 

  1. Mazidi M, Karimi E, Rezaie P, Ferns GA. Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. J Diabetes Complications. 2017;31(7):1237-1242. doi: 10.1016/j.jdiacomp.2016.05.022

 

  1. Mosenzon O, Capehorn MS, De Remigis A, Rasmussen S, Weimers P, Rosenstock J. Impact of semaglutide on high-sensitivity C-reactive protein: Exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. Cardiovasc Diabetol. 2022;21(1):172. doi: 10.1186/s12933-022-01585-7

 

  1. Cui QN, Stein LM, Fortin SM, Hayes MR. The role of glia in the physiology and pharmacology of glucagon‐like peptide‐1: Implications for obesity, diabetes, neurodegeneration and glaucoma. Br J Pharmacol. 2021;179(4):715-726. doi: 10.1111/bph.15683

 

  1. Ludwig MQ, Todorov PV, Egerod KL, Olson DP, Pers TH. Single-cell mapping of GLP-1 and GIP receptor expression in the dorsal vagal complex. Diabetes. 2021;70(9):1945-1955. doi: 10.2337/dbi21-0003

 

  1. Spielman LJ, Gibson DL, Klegeris A. Incretin hormones regulate microglia oxidative stress, survival and expression of trophic factors. Eur J Cell Biol. 2017;96(3):240-253. doi: 10.1016/j.ejcb.2017.03.004

 

  1. Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors for ischemic stroke. Stroke. 2003;34(10):2518-2532. doi: 10.1161/01.STR.0000089015.51603.CC

 

  1. Helmstädter J, Frenis K, Filippou K, et al. Endothelial GLP-1 (glucagon-like peptide-1) receptor mediates cardiovascular protection by liraglutide in mice with experimental arterial hypertension. Arterioscler Thromb Vasc Biol. 2020;40(1):145-158. doi: 10.1161/atv.0000615456.97862.30

 

  1. Liu CC, Ko HJ, Liu WS, et al. Neutrophil-to-lymphocyte ratio as a predictive marker of metabolic syndrome. Medicine (Baltimore). 2019;98(43):e17537. doi: 10.1097/MD.0000000000017537

 

  1. Hoh BL, Chimowitz MI. Focused update on intracranial atherosclerosis: Introduction, highlights, and knowledge gaps. Stroke. 2024;55(2):305-310. doi: 10.1161/STROKEAHA.123.045513

 

  1. Ying Y, Yu F, Luo Y, et al. Neutrophil-to-lymphocyte ratio as a predictive biomarker for stroke severity and short-term prognosis in acute ischemic stroke with intracranial atherosclerotic stenosis. Front Neurol. 2021;12:705949. doi: 10.3389/fneur.2021.705949

 

  1. Chen G, Che L, Lai M, et al. Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: A prospective cohort study. BMC Endocr Disord. 2024;24:64. doi: 10.1186/s12902-024-01592-7

 

  1. Den Hertog HM, van Rossum JA, van der Worp HB, et al. C-reactive protein in the very early phase of acute ischemic stroke: Association with poor outcome and death. J Neurol. 2009;256(12):2003-2008. doi: 10.1007/s00415-009-5228-x

 

  1. Ridker PM, Buring JE, Cook NR, Rifai N. C-Reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: An 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003;107(3):391-397. doi: 10.1161/01.CIR.0000055014.62083.05

 

  1. Rost NS, Wolf PA, Kase CS, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack. Stroke. 2001;32(11):2575-2579. doi: 10.1161/hs1101.098151

 

  1. Verma S, Bhatta M, Davies M, et al. Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials. EClinicalMedicine. 2023;55:101737. doi: 10.1016/j.eclinm.2022.101737

 

  1. Martínez-Martínez E, Cachofeiro V. Oxidative Stress in Obesity. Antioxidants (Basel). 2022;11(4):639. doi: 10.3390/antiox11040639

 

  1. Manzanero S, Santro T, Arumugam TV. Neuronal oxidative stress in acute ischemic stroke: Sources and contribution to cell injury. Neurochem Int. 2013;62(5):712-718. doi: 10.1016/j.neuint.2012.11.009

 

  1. Oh YS, Jun HS. Effects of glucagon-like peptide-1 on oxidative stress and Nrf2 signaling. Int J Mol Sci. 2017;19(1):26. doi: 10.3390/ijms19010026

 

  1. Feng S, Yang M, Liu S, He Y, Deng S, Gong Y. Oxidative stress as a bridge between age and stroke: A narrative review. J Intensive Med. 2023;3(4):313-319. doi: 10.1016/j.jointm.2023.02.002

 

  1. Wu L, Xiong X, Wu X, et al. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci. 2020;13:28. doi: 10.3389/fnmol.2020.00028

 

  1. Enzmann G, Kargaran S, Engelhardt B. Ischemia-reperfusion injury in stroke: Impact of the brain barriers and brain immune privilege on neutrophil function. Ther Adv Neurol Disord. 2018;11:1756286418794184. doi: 10.1177/1756286418794184

 

  1. Van Dyken P, Lacoste B. Impact of metabolic syndromeon neuroinflammation and the blood-brain barrier. Front Neurosci. 2018;12:930. doi: 10.3389/fnins.2018.00930

 

  1. Zhong C, Yang J, Xu T, et al. Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke. Neurology. 2017;89(8):805-812. doi: 10.1212/WNL.0000000000004257

 

  1. Ramos-Fernandez M, Bellolio MF, Stead LG. Matrix metalloproteinase-9 as a marker for acute ischemic stroke: A systematic review. J Stroke Cerebrovasc Dis. 2011;20(1):47-54. doi: 10.1016/j.jstrokecerebrovasdis.2009.10.008

 

  1. Turner RJ, Sharp FR. Implications of MMP9 for blood brain barrier disruption and hemorrhagic transformation following ischemic stroke. Front Cell Neurosci. 2016;10:56. doi: 10.3389/fncel.2016.00056

 

  1. Hopps E, Caimi G. Matrix metalloproteinases in metabolic syndrome. Eur J Intern Med. 2012;23(2):99-104. doi: 10.1016/j.ejim.2011.09.012

 

  1. Gonçalves FM, Jacob-Ferreira ALB, Gomes VA, et al. Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome. Clin Chim Acta. 2009;403(1):173-177. doi: 10.1016/j.cca.2009.02.013

 

  1. Lu W, Wen J. Crosstalk among glial cells in the blood-brain barrier injury after ischemic stroke. Mol Neurobiol. 2024;61(9):6161-6174. doi: 10.1007/s12035-024-03939-6

 

  1. Cosentino F, Rubattu S, Savoia C, Venturelli V, Pagannonne E, Volpe M. Endothelial dysfunction and stroke. J Cardiovasc Pharmacol. 2001;38:S75-S78. doi: 10.1097/00005344-200111002-00018

 

  1. Augestad IL, Dekens D, Karampatsi D, et al. Normalisation of glucose metabolism by exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice. Br J Pharmacol. 2022;179(4):677-694. doi: 10.1111/bph.15524

 

  1. Acquaro M, Turco A, De Luca L. The clinical and pharmacoeconomic impact of established and novel heart failure therapies. Eur Heart J Suppl. 2025;27(Supplement_1):i132-i136. doi: 10.1093/eurheartjsupp/suae118

 

  1. Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime health effects and cost-effectiveness of tirzepatide and semaglutide in US adults. JAMA Health Forum. 2025;6(3):e245586. doi: 10.1001/jamahealthforum.2024.5586

 

  1. Malhotra K, Katsanos AH, Lambadiari V, et al. GLP-1 receptor agonists in diabetes for stroke prevention: A systematic review and meta-analysis. J Neurol. 2020;267(7):2117-2122. doi: 10.1007/s00415-020-09813-4

 

  1. Anderson JE, Butler J, Alexandrov AV. Reducing ischemic stroke in diabetes: The role of GLP-1 RAs. J Fam Pract. 2023;72(6 Suppl):S55-S60. doi: 10.12788/jfp.0624

 

  1. Yang X, Qiang Q, Li N, Feng P, Wei W, Hölscher C. Neuroprotective mechanisms of glucagon-like peptide- 1-based therapies in ischemic stroke: An update based on preclinical research. Front Neurol. 2022;13:844697. doi: 10.3389/fneur.2022.844697
Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept