OBJECTIVES: To determine the cost-effectiveness of dapagliflozin versus sulfonylureas for the treatment of patients with type 2 diabetes mellitus (T2DM) who have failed metformin monotherapy. METHODS: A cost-effectiveness analysis was made by a discrete events model at the patient’s level that simulates the incidence of the complications of the disease, and it considers a time horizon of 20 years. The model perspective is from the Colombian health system. The main outcomes are the quality-adjusted life years (QALY) and the economic results of the disease and it complications. Direct costs were updated to the year 2016 and a discount rate of 5 % was applied, both for costs and for health outcomes. The risks of developing complications were taken from the risk formulas of UKPDS68 and UKPDS66. RESULTS: Dapagliflozin is not inferior than sulfonylureas in terms of health outcomes of HbA1c, cholesterol and HDL. Patients with dapagliflozin lost weight (-3.22 kg) and decreased more the systolic blood pressure (-4.3 mmHg); they also had fewer hypoglycemic events (3.5 %) than patients with sulfonylureas (40.8 %), with US $ 1,660 savings. Dapagliflozin generates more 0.41 discounted QALY than sulfonylureas and has an ICER of US $ 6,144 per patient. In the willingness to pay curves, dapagliflozin has a 65.5 % probability of being the choice strategy with a willingness to pay value of US $ 6,049, which is the value of a GDP per capita in Colombia. CONCLUSIONS: From the perspective of the Colombian health system, dapagliflozin is a cost-effective strategy versus sulfonylureas in patients with T2DM inadequately controlled with metformin monotherapy; dapagliflozin has a great impact over patient weight loss and a decreased systolic blood pressure, as well as fewer hypoglycemic events.