OBJECTIVES: To evaluate the CE ratio of empagliflozin 25mg compared to sitagliptin 100mg when added to MET in patients with T2DM. METHODS: A discrete event simulation CE model was developed to assess the life years (LY) gained and the treatment related costs associated with the studied alternatives in a 10-year horizon. Relevant clinical outcomes identified where efficacy (HbA1c, systolic blood pressure and weight reductions), safety (severe and non-severe hypoglycemia episodes, urinary and genital infections) and treatment-related complications including discontinuation. The results of a Network-Meta-Analysis where taken as efficacy and safety inputs of the model. Public institutional direct medical costs (2014 purchases and price tabulators) where retrieved to adopt the national health system perspective. A probabilistic sensitivity analysis was performed to endorse the results. RESULTS: In the 10-year time horizon adopted, and after running 5000 simulations per treatment arm, sitaglitpin 100mg was estimated to have the highest cost of treatment with $179,124.75 MX against $175,842.69 MX reported by empagliflozin 25mg. A small positive difference of 0.009 in LY gained was to be seen in the empagliflozin 25mg arm with an estimate of 4.166 when compared to the sitagliptin 100mg arm with 4.157. Results in the incremental CE ratio (ICER) favored empagliflozin 25mg as a dominant therapy against sitagliptin 100mg. Results were sensitive to changes in efficacy inputs and costs; probabilistic results were scattered, with a discrete trend towards the cost-saving and cost-effective planes. CONCLUSIONS: With a lower cost of treatment at a better LY saved level, empagliflozin was estimated to be a cost-saving alternative versus sitagliptin when added to MET for patients with T2DM.