OBJECTIVES Canagliflozin is a novel drug for treatment of diabetes belonging to the drug class known as sodium glucose co-transporter-2 (SGLT2) inhibitors which method of action is insulin independent. Canagliflozin has been shown to not only reduce glucose levels, but also weight and blood pressure. The objective is to evaluate the cost-effectiveness of canagliflozin 100mg in dual therapy (add-on to metformin) compared to sitagliptin and glimepiride, in triple therapy (add-on to metformin and sulfonylurea) compared to sitagliptin and as an insulin add-on compared to dapagliflozin in the Czech Republic setting from a payer perspective. METHODS The IMS CORE Diabetes Model was used to evaluate the cost-effectiveness of canagliflozin using clinical trial data and network meta-analysis data, combined with Czech Republic specific data, where available. RESULTS The cost-effectiveness analyses indicate that in dual therapy when compared with sitagliptin and glimepiride, canagliflozin 100mg is found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of 242,783 Kč per QALY gained and 626,939 Kč per QALY gained, respectively. In triple therapy when compared to sitagliptin, canagliflozin 100mg is found to be cost-effective with an ICER of 335,759 Kč per QALY gained. As an add-on to insulin (with or without metformin), canagliflozin compared to dapagliflozin appears to be cost-effective with an ICER of 375 Kč per QALY gained. A wide range of deterministic sensitivity analyses revealed that in the majority of scenarios, canagliflozin remained cost-effective with ICERs well below the willingness-to-pay threshold of 1,100,000 Kč per QALY. CONCLUSIONS Canagliflozin 100mg represents a cost-effective option for the treatment of type 2 diabetes in the Czech Republic. Canagliflozin 100mg offers greater health benefits than the included alternatives in this study, at a cost that provides good value for money.