OBJECTIVES Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor developed for the treatment of adult patients with type 2 diabetes mellitus (T2DM). To evaluate the cost-effectiveness of canagliflozin in dual therapy as add-on to metformin (MET) compared to sitagliptin, and in triple therapy (add on to MET and sulphonylurea (SU)) compared to sitagliptin, liraglutide and a mixed strategy with both drugs. METHODS The IMS CORE Diabetes Model was used to evaluate the cost-effectiveness of canagliflozin versus the aforementioned comparators using French-specific data, where available. RESULTS In dual therapy, as add-on to metformin versus sitagliptin, canagliflozin (100 mg and 300 mg weighted average 50:50) resulted in an incremental cost of 392 € and an average QALY gain of 0.013, which leads to an ICER of 30,154 €. In triple therapy canagliflozin (100 mg and 300 mg weighted average 50:50) dominates sitagliptin with average cost savings of 286 € and an average QALY gain of 0.050. Canagliflozin was estimated to be cost-saving (1,280 €) compared to liraglutide (distribution liraglutide 1.2 mg / 1.8 mg= 0.71/0.29 based on French market research data) with incremental QALYs of -0.015. Canagliflozin (100 mg and 300 mg weighted average 50:50) dominates a mixed strategy with liraglutide (12.5%) and sitagliptin (87.5%) average cost saving of 410 € and average QALY gain of 0.041. Sensitivity analyses showed that HbAand SBP treatment effects were key drivers of the cost effectiveness results. CONCLUSIONS Canagliflozin 100 mg and 300 mg will be a cost-effective alternative to sitagliptin in dual therapy as add-on to metformin. In triple therapy as add-on to metformin and SU, canagliflozin dominates in comparison with a mix of patients treated with sitagliptin or liraglutide. Canagliflozin 100 mg or 300 mg is expected to be considered good value for money for the treatment of T2DM in France.