We conducted a network meta-analysis (NMA) to comprehensively evaluate the prophylactic benefits of these agents across multiple neurodegenerative diseases and identify the most promising preventive strategies.<h4>Methods</h4>We systematically searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov through October 24th, 2024, for randomized controlled trials (RCTs) of GLP-1 receptor agonists or SGLT2 inhibitors. This evidence concerns the gene SLC5A2 and neurodegenerative disease.