OBJECTIVES Canagliflozin is a novel drug for treatment of diabetes belonging to the drug class known as sodium glucose co-transporter–2 (SGLT-2) inhibitors. To evaluate the cost-effectiveness of canagliflozin 100 mg in the Slovakian setting from a payer perspective when compared to sitagliptin in dual therapy (add-on to metformin), sitagliptin in triple therapy (add-on to metformin plus sulfonylurea) and dapagliflozin in combination with insulin (with or without metformin). METHODS The IMS CORE Diabetes Model was used to evaluate the cost-effectiveness of canagliflozin versus comparators using Slovakia specific data, where available. RESULTS The cost-effectiveness analyses indicated that canagliflozin 100 mg in dual therapy when compared with sitagliptin, was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of 14,930 € per QALY gained. In triple therapy when compared to sitagliptin, canagliflozin 100 mg was found to be cost-effective with an ICER of 5,251 € per QALY gained and in combination with insulin, canagliflozin 100 mg was a dominant alternative compared to dapagliflozin with a cost saving of 118 € per patient and higher QALYs. One-way sensitivity analyses revealed that in the majority of scenarios considered canagliflozin remained cost-effective in the dual therapy, triple therapy and add-on to insulin comparisons. CONCLUSIONS Based on calculations performed using the CORE Diabetes model, canagliflozin 100 mg appear to represent a cost-effective option for the treatment of type 2 diabetes in Slovakia. Canagliflozin 100 mg was found to offer greater health benefits than currently available alternatives and to be a cost-effective treatment option when used in dual and triple therapy instead of sitagliptin or as an add-on to insulin instead of dapagliflozin.