Background&#xa0; <p>Some Asian countries have less developed pharmacovigilance systems than in the West. Generally, SGLT2 inhibitors, as the newest antidiabetic agent, and sulfonylureas can be utilized as Metformin add-ons for second-line therapy.</p> Objective&#xa0; <p> This study aims to evaluate the safety profile of SGLT2 inhibitors against sulfonylureas in Asian people with type 2 diabetes.</p> Methods <p>This is the first head-to-head meta-analysis comparing the safety of SGLT2 inhibitors and sulfonylureas in the Asian population. The protocol (CRD420234480943) has been formally registered with Prospero.</p> Results <p>A search from CENTRAL, PubMed, and EMBASE databases until February 15, 2024, yielded six RCTs. The findings of the risk of bias analysis using the RoB2 suggest that there are two publications with low risk, two with some concern, and two with high-risk ratings. Meanwhile, data synthesis using Mantel–Haenszel statistical methods via the RevMan 5.3 program reveals that SGLT2 inhibitors considerably lower the incidence of hypoglycemia when compared to sulfonylureas. SGLT2 inhibitor use shows no significant difference in genital or urinary tract infection incidences, though evidence remains inconclusive due to limited statistical power</p> Conclusion <p>SGLT2 inhibitors are thought to be better tolerated in Asian T2DM patients. To confirm this evidence in ordinary clinical practice, extensive real-world research on Asians is required.</p>