OBJECTIVES: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium-glucose co-transporter -2 inhibitor) versus glimepiride (a widely used sulfonylureas), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: Literature screening, meta-analysis and indirect comparison were used to evaluate the efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local source and reported in 2015 Chinese Renminbi (RMB). A discount rate of 3% was applied to both costs and health effects. The Cardiff model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes, was used to generate outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs and quality-adjusted life years (QALYs) over a time horizon of 40 years from the societal perspective. Univariate and probabilistic sensitivity analyses were performed to assess uncertainty in the model results. RESULTS: Compared with glimepiride, patients on dapagliflozin gained 0.96 QALYs, at an incremental cost saving of RMB 52,380 in our simulated cohort. This resulted in a cost saving of RMB 54,602 per QALY gained with dapagliflozin. The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis CONCLUSIONS: Compared with glimepiride, dapagliflozin as monotherapy for T2DM is a more cost-effective treatment in China