The Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists on Peripheral Neuropathy Among Diabetic Patients: A Systematic Review

Background: Diabetic peripheral neuropathy (DPN) is a highly prevalent complication of diabetes mellitus, affecting sensory, motor, and autonomic nerves. It leads to neuropathic pain, loss of sensation, and increased risk of foot ulceration and amputation. While glycemic control slows progression, few therapies modify disease course. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for diabetes management and cardiovascular protection, and emerging evidence suggests potential neuroprotective effects. Objective: To systematically review clinical evidence assessing the effects of GLP-1 receptor agonists on peripheral neuropathy in diabetic patients. Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify randomized controlled trials, observational studies, and meta-analyses evaluating GLP-1 RAs and peripheral neuropathy outcomes. Outcomes included nerve conduction studies, neuropathy symptom scores, nerve morphology, and electrophysiological measures. Risk of bias was assessed using standardized methodological quality tools. Results: Fifteen studies met inclusion criteria: seven randomized controlled trials, five observational studies, and three meta-analyses. GLP-1 RA therapy was associated with improved nerve conduction velocity and structural nerve parameters. Some studies reported modest improvements in neuropathic pain and clinical scores, though findings were inconsistent. Several benefits appeared independent of glycemic control, suggesting potential direct neuroprotective mechanisms. Conclusion: GLP-1 receptor agonists show promise for improving neurophysiological and structural markers of diabetic peripheral neuropathy. Further large, long-term randomized trials are needed to determine clinical significance and confirm disease-modifying effects.