OBJECTIVES: To estimate the cost-effectiveness of using CANA versus DAPA or EMPA, three agents that inhibit sodium glucose co-transporter 2 (SGLT2), as monotherapy from the UK NHS perspective. METHODS: The validated ECHO-T2DM model was used to estimate 40-year outcomes and costs associated with using CANA 100 or 300mg versus DAPA 10mg or EMPA 25mg.  Data from a 26-week network meta-analysis (NMA) performed to support a NICE multiple technology assessment were used to populate the model with treatment effects for HbA1c, blood pressure, weight and rates of hypoglycaemic events (hypoglycaemia data for EMPA were not possible to report from the NMA).  Changes in lipids and rates of adverse events (AEs) associated with SGLT2 inhibition (i.e., urinary tract infections, genital mycotic infections) were sourced from a CANA monotherapy trial; values for DAPA and EMPA were assumed the same as CANA 100mg (as was the hypoglycaemia rate for EMPA).  Sensitivity analyses were also performed. RESULTS: In the base case, CANA 100mg dominated DAPA and EMPA with quality-adjusted life-year (QALY) gains of 0.033 and 0.015 and lower total costs of £69 and £3.  CANA 300mg versus DAPA provided an estimated QALY gain of 0.075 and increased cost of £709, resulting in an incremental cost-effectiveness ratio (ICER) of £9,429.  Versus EMPA, the ICER was slightly higher (£13,491), but still below the generally accepted threshold in the UK, with a QALY gain of 0.056 and an increased cost of £761.  Sensitivity analyses supported these base case findings. CONCLUSIONS: Through an insulin-independent mechanism of action, agents that inhibit SGLT2 improve glucose levels, blood pressure, and weight, with a low inherent risk of hypoglycaemia.  These results suggest that both CANA 100 and 300mg are likely to be cost-effective monotherapy options versus DAPA and EMPA in the UK.