OBJECTIVES Two SGLT-2 inhibitors, CANA and DAPA, are recommended in the UK for combination therapy in T2DM. Through an insulin-independent mechanism of action, SGLT-2 inhibitors improve glucose levels, blood pressure, and weight with a low inherent risk of hypoglycaemia. The cost-effectiveness of using CANA or DAPA in combination with MET was evaluated in patients inadequately controlled with MET monotherapy, from the perspective of the UK NHS. METHODS The ECHO-T2DM model was used to estimate 40-year outcomes and costs associated with using CANA (100mg or 300mg) versus DAPA 10mg in dual therapy.  HbA1c efficacy estimates were obtained from a Network Meta-Analysis (NMA). Analyses of pooled data from trials investigating CANA dual therapy (with MET) were used for parameters unavailable in the NMA (i.e., SBP, LDL, HDL and AEs). A broad set of sensitivity analyses were performed. RESULTS Both doses of CANA were associated with more QALYs (0.01, 0.03 for 100mg and 300mg, respectively) and higher costs (£101, £594, respectively). The associated incremental cost-effectiveness ratios (ICERs) were £7,423 and £17,734, respectively; both below the willingness-to-pay for QALY threshold in the UK.  The key driver of the result for CANA 300mg was the greater HbA1c efficacy versus DAPA 10mg, and for CANA 100mg, a lower need for insulin rescue since CANA (but not DAPA) can be used in persons with moderate renal impairment. The ICERs were robust under all scenarios tested. Only use of UK-specific and not clinical trial patient characteristics substantively impacted the results; none reversed the interpretation of CANA as cost-effective versus DAPA. CONCLUSIONS SGLT-2 inhibitors reduce HbA1C, body weight, and blood pressure, and thus the risk of micro- and macrovascular complications.  Economic simulations suggest that both doses of CANA are cost-effective versus DAPA in dual therapy treatment of T2DM (with MET) in the UK.