OBJECTIVES: To evaluate the cost-effectiveness of canagliflozin in dual therapy as add-on to metformin compared to sitagliptin and glimepiride, as add on to insulin (plus metformin) and in mono therapy compared to sulfonylurea in the Swedish setting from a societal perspective.  METHODS: The IMS CORE Diabetes Model was used to evaluate the cost-effectiveness of canagliflozin (using a weighted average of 80/20 for the 100 mg and 300 mg dosage respectively) versus the aforementioned comparators using Swedish-specific data, where available. Direct and indirect costs were reported in 2012 Euro [1 Euro (€) = 8.91 Swedish Krona] and an annual discount rate of 3% was applied on costs and effects.  RESULTS: With inclusion of indirect costs the cost-effectiveness analyses indicate that in dual therapy when compared to sitagliptin as add-on to metformin, canagliflozin appears to dominate sitagliptin with average cost savings of 718 € and an average QALY gain of 0.011 and as add-on to metformin canagliflozin appears to dominate sulfonylurea with average cost savings of 600 € and an average QALY gain of 0.063. As add-on to insulin canagliflozin appears to dominate placebo with an incremental cost saving of 3339 € and an incremental QALY of 0.054. In mono therapy canagliflozin is cost-effective compared to sulfonylurea with an incremental cost-effectiveness ratio (ICER) of 1838 € per QALY. Probabilistic analysis of the four comparisons suggests a likelihood of above 50% of canagliflozin being cost-effective. Sensitivity analyses show that canagliflozin remains cost-effective when indirect costs were not included. CONCLUSIONS: Canagliflozin 100 mg and 300 mg (80/20 dose split) appears to be a cost-effective alternative to sitagliptin and glimepiride in dual therapy as add-on to metformin. Adding canagliflozin to insulin will be cost-effective compared with placebo. Canagliflozin is a cost-effective alternative to sulfonylurea in mono therapy.