OBJECTIVES: CANA, an agent that inhibits sodium glucose co-transporter 2, decreases glucose levels by lowering the renal threshold for glucose excretion, thereby resulting in an increase in urinary glucose excretion (UGE).  This increase in UGE reduces weight, as well as systolic blood pressure (SBP).  In contrast, dipeptidyl peptidase-4 inhibitors such as SITA lower glucose but are not associated with weight loss or a reduction in SBP.  The objective of this analysis was to evaluate the cost-effectiveness of CANA 100 and 300 mg versus SITA 100 mg in dual therapy and triple therapy as an add-on to metformin and as an add-on to metformin plus sulphonylurea, respectively, from the Spanish National Health System perspective. METHODS: The IMS CORE Diabetes Model was used to evaluate the cost-effectiveness of CANA 100 and 300 mg versus SITA using Spanish-specific utilities and cost data.  Direct costs were reported in euros and an annual discount rate of 3% was applied on costs and effects.  The time horizon used for the economic evaluation was 40 years to reflect the chronic nature of the disease.  Patient characteristics, treatment effects, and safety were sourced from direct comparisons using clinical trial data for CANA.  Results were compared with the willingness-to-pay (WTP) threshold reported for Spain (€30,000/QALY). RESULTS: Results suggest that CANA 100 mg dominates SITA in dual therapy and in triple therapy, with estimated quality-adjusted life year (QALY) gains of 0.027 and 0.057, respectively.  CANA 300 mg is cost-effective compared to SITA in dual and triple therapy, with a cost-effectiveness ratio below the WTP threshold in Spain; QALY gains were 0.060 and 0.075, respectively. CONCLUSIONS: These results suggest that adding CANA 100 or 300 mg instead of SITA in patients inadequately controlled on metformin or metformin plus sulphonylurea would result in more efficient use of healthcare resources in the Spanish setting.