OBJECTIVES:  To evaluate the cost-effectiveness of dapagliflozin compared with a sulfonylurea (SU) when added to metformin in persons with T2DM poorly controlled with metformin alone, in Dominican Republic and Guatemala. METHODS:  A discrete event simulation model (Cardiff diabetes model), based on UKPDS 68 was used to simulate disease progression and to estimate the economic and health treatment consequences in people with T2DM. Epidemiologic and clinical efficacy parameters were obtained from the literature. Cost of drugs was obtained from country level price data; cost of macro and microvascular events were estimated based on tariffs from social security system and consultation with local experts of Guatemala and Dominican Republic. Costs were expressed in US-Dollars ($). A 20-year time horizon and the payer’s perspective were assumed. Costs and health outcomes were discounted at 3,5% and 5% in Guatemala and Dominican Republic, respectively. Deterministic and probabilistic sensitivity analysis (PAS) were performed. RESULTS:  Dapagliflozin add-on to metformin, compared to SU addition was associated with an incremental benefit of 0.362 QALYs (95%CI: 0.360; 0.365) in Guatemala and 0.331 QALYs (95%CI: 0.329; 0.333) in Dominican Republic. In the both countries the total cost of dapagliflozin cohort was higher than that of SU one (Incremental cost: Guatemala: $3,683; Dominican Republic: $3,295). The calculated Incremental Cost-Effectiveness Ratio (ICER) were $10,171 and $9,948 per QALY, in Guatemala and Dominican Republic, respectively. Using WHO's criteria; dapagliflozin compared to SU treatment strategy has a 99% probability for Guatemala and 100% for the Dominican Republic of being cost-effective (ICER< 3 GDP). The results were robust to sensitivity analysis. CONCLUSIONS:  The data show that in Guatemala and the Dominican Republic, according to WHO’s criteria, dapagliflozin in combination with metformin would be a cost-effective treatment option for patients who are inadequately controlled with metformin monotherapy.