OBJECTIVES: Dapagliflozin, a sodium-glucose-transporter-protein-2 (SGLT2) inhibitor, can serve as a treatment for type 2 diabetes mellitus (T2DM) in patients inadequately controlled on metformin mono-therapy. The relative health benefits and costs of dapagliflozin compared to a dipeptidyl-peptidase-4 inhibitor (DPP4), added to metformin, were assessed through a cost-effectiveness analysis (CEA) from a Turkish payer perspective. METHODS: For the current CEA, a micro-simulation disease model (CARDIFF) was used. Clinical inputs were derived from a systematic review and network meta-analysis, along with a long-term follow-up study for dapagliflozin. In addition, Turkish specific cost data were collected and applied. The model predicted micro-and macro-vascular complications based on the UKPDS equations. Total Quality‑Adjusted-Life-Years (QALYs) and costs were calculated over a lifetime horizon. Deterministic, probabilistic sensitivity analyses and elaborate scenario analyses were performed. RESULTS: Compared to DPP4, dapagliflozin was associated with an incremental benefit of 0.590 QALYs (95% CI: 0.038; 1.232) and cost savings of 494₺ (95% CI: -1,727₺; 889₺). Results were sensitive to changes in treatments’ effect on weight and HbA1c, and in utility values related to weight changes. Dapagliflozin’s higher health benefits and cost savings are mainly explained by its greater beneficial effect on weight, leading to higher QALYs and less drug costs for dapagliflozin patients. The lower treatment costs are related to the insulin treatment costs (i.e. subsequent line regimens) due to the lower weight of dapagliflozin patients observed over time, which eventually leads to lesser insulin dosage. CONCLUSIONS: Dapagliflozin is a cost-saving strategy with higher health benefits compared to DPP4, added to metformin, for Turkish T2DM patients inadequately controlled on metformin mono-therapy.