GLP-1 Receptor Agonists: Beyond Diabetes-What the Neurosurgeon Needs to Know

Overview

Journal Neurosurg Pract

Specialty Neurology

Date 2025 Feb 17

PMID 39959894

Authors

Hael Abdulrazeq

Mazen Taman

Rohaid Ali

Cody Doberstein

Patricia Sullivan

Prakash Sampath

Albert Telfeian

Ziya Gokaslan

Jared Fridley

Wael Asaad

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained increasing popularity since the approval of semaglutide by the United States Food and Drug Administration for chronic weight management. Significant benefits have been noted in glycemic control and cardiovascular health. However, as increasing numbers of patients are started on these medications, it is important for neurosurgeons to have knowledge of any perioperative considerations and side effects related to this class of drugs.

Methods: We performed a qualitative literature review using the PubMed and Embase databases, using the following key words: GLP-1 RAs adverse events; GLP-1 RAs and anesthesia; substance use disorders; and addiction, functional neurosurgery, nervous system rehabilitation, and spinal cord injury. Articles of relevance to perioperative management of these medications and specific benefits in the neurosurgical field were discussed.

Results: Recent guidance from the American Society of Anesthesiologists demonstrates the importance of tailored management of GLP-RA drugs for surgical patients. In addition, certain positive effects have been noted with relation to substance use disorders, neural protection and rehabilitation, and neurodegenerative disorders such as Alzheimer's disease.

Conclusion: In this article, we review what the neurosurgeon needs to know about the perioperative management of GLP-1 RAs and discuss existing literature in clinical and preclinical studies for potential indications and benefits of these medications, which can influence the management of conditions treated by neurosurgeons.

References

Ushakumari D, Sladen R . ASA Consensus-based Guidance on Preoperative Management of Patients on Glucagon-like Peptide-1 Receptor Agonists. Anesthesiology. 2023; 140(2):346-348. DOI: 10.1097/ALN.0000000000004776. View

Vandemark C, Nguyen J, Zhao Z . Cardiovascular Protection with a Long-Acting GLP-1 Receptor Agonist Liraglutide: An Experimental Update. Molecules. 2023; 28(3). PMC: 9921762. DOI: 10.3390/molecules28031369. View

Husain M, Birkenfeld A, Donsmark M, Dungan K, Eliaschewitz F, Franco D . Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019; 381(9):841-851. DOI: 10.1056/NEJMoa1901118. View

Iwai T, Suzuki M, Kobayashi K, Mori K, Mogi Y, Oka J . The influences of juvenile diabetes on memory and hippocampal plasticity in rats: improving effects of glucagon-like peptide-1. Neurosci Res. 2009; 64(1):67-74. DOI: 10.1016/j.neures.2009.01.013. View

Nizari S, Basalay M, Chapman P, Korte N, Korsak A, Christie I . 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. PMC: 8093159. DOI: 10.1007/s00395-021-00873-9. View

Nomura S, Katoh H, Yanagisawa S, Noguchi T, Okada K, Watanabe M . Administration of the GLP-1 receptor agonist exenatide in rats improves functional recovery after spinal cord injury by reducing endoplasmic reticulum stress. IBRO Neurosci Rep. 2023; 15:225-234. PMC: 10562917. DOI: 10.1016/j.ibneur.2023.09.003. View

Sun F, Chai S, Yu K, Quan X, Yang Z, Wu S . Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes Technol Ther. 2014; 17(1):35-42. PMC: 4290796. DOI: 10.1089/dia.2014.0188. View

Xie Z, Enkhjargal B, Nathanael M, Wu L, Zhu Q, Zhang T . Exendin-4 Preserves Blood-Brain Barrier Integrity Glucagon-Like Peptide 1 Receptor/Activated Protein Kinase-Dependent Nuclear Factor-Kappa B/Matrix Metalloproteinase-9 Inhibition After Subarachnoid Hemorrhage in Rat. Front Mol Neurosci. 2022; 14:750726. PMC: 8733623. DOI: 10.3389/fnmol.2021.750726. View

McClean P, Gault V, Harriott P, Holscher C . Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer's disease. Eur J Pharmacol. 2009; 630(1-3):158-62. DOI: 10.1016/j.ejphar.2009.12.023. View

10.

Singh S, Chang H, Richards T, Weiner J, Clark J, Segal J . Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med. 2013; 173(7):534-9. DOI: 10.1001/jamainternmed.2013.2720. View

11.

Hara H, Kanayama M, Oha F, Shimamura Y, Watanabe T, Hashimoto T . Effect of pre-operative HbA1c and blood glucose level on the surgical site infection after lumbar instrumentation surgery. J Orthop Sci. 2023; 29(5):1168-1173. DOI: 10.1016/j.jos.2023.08.015. View

12.

Heinla K, Vasar E, Reppo I, Sedman T, Volke V . GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers. Diabetes Ther. 2023; 14(4):777-786. PMC: 10064408. DOI: 10.1007/s13300-023-01381-w. View

13.

Kaneto H, Kimura T, Shimoda M, Obata A, Sanada J, Fushimi Y . Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus. Biomedicines. 2022; 10(4). PMC: 9030375. DOI: 10.3390/biomedicines10040818. View

14.

Mehta D, Praecht A, Ward H, Sanches M, Sorkhou M, Tang V . A systematic review and meta-analysis of neuromodulation therapies for substance use disorders. Neuropsychopharmacology. 2023; 49(4):649-680. PMC: 10876556. DOI: 10.1038/s41386-023-01776-0. View

15.

Castle-Kirszbaum M, Tee J, Chan P, Hunn M . Obesity in Neurosurgery: A Narrative Review of the Literature. World Neurosurg. 2017; 106:790-805. DOI: 10.1016/j.wneu.2017.06.049. View

16.

Leggio L, Hendershot C, Farokhnia M, Fink-Jensen A, Klausen M, Schacht J . GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nat Med. 2023; 29(12):2993-2995. DOI: 10.1038/s41591-023-02634-8. View

17.

Gumuslu E, Mutlu O, Celikyurt I, Ulak G, Akar F, Erden F . Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice. Fundam Clin Pharmacol. 2016; 30(4):376-84. DOI: 10.1111/fcp.12192. View

18.

Chen H, Wu Z, Chen D, Huang F . Correlation between blood glucose level and poor wound healing after posterior lumbar interbody fusion in patients with type 2 diabetes. Int Wound J. 2023; 21(1):e14340. PMC: 10777750. DOI: 10.1111/iwj.14340. View

19.

Marso S, Bain S, Consoli A, Eliaschewitz F, Jodar E, Leiter L . Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375(19):1834-1844. DOI: 10.1056/NEJMoa1607141. View

20.

Holscher C . Potential role of glucagon-like peptide-1 (GLP-1) in neuroprotection. CNS Drugs. 2012; 26(10):871-82. DOI: 10.2165/11635890-000000000-00000. View