OBJECTIVES: To inform a multiple technology appraisal to be conducted by the National Institute for Health and Care Excellence on the use of agents that inhibit sodium-glucose co-transporter 2 (SGLT2), canagliflozin was assessed as monotherapy treatment for T2DM. METHODS: A systematic literature review identified 36 trials, which were used to perform a Bayesian NMA to estimate the relative efficacy (HbA1c, weight, and systolic blood pressure [SBP]) of canagliflozin monotherapy at 26±4 weeks compared to dipeptidyl peptidase-4 inhibitors (DPP-4s), sulphonylurea, pioglitazone, and SGLT2 inhibitors.  Networks of evidence had treatment- and dose-specific nodes for DPP-4s, pioglitazone, and SGLT2 inhibitors. Relative efficacy was evaluated based on absolute differences and Bayesian probabilities (P), where 30%< P >70% were chosen to indicate a smaller and larger effect, respectively. RESULTS: Results presented here focus on comparisons to the most relevant anti-hyperglycaemic therapies in the UK; sitagliptin, gliclazide, pioglitazone, dapagliflozin 10mg, and empagliflozin 10mg/25mg. Canagliflozin 300mg was associated with greater reductions in HbA1c (Δ–0.29 to –0.52) versus all comparators. Canagliflozin 100mg conferred reductions in HbA1c at least as large as other comparator (Δ–0.03 to –0.26). Canagliflozin was associated with larger reductions in weight (kg) versus all comparators (Δ–0.41 to –7.03), except for canagliflozin 100mg versus empagliflozin 25mg, where the reduction was similar (Δ–0.19). Canagliflozin 300mg was associated with larger reductions in SBP (Δ–1.06 to –6.29) versus all comparators. Canagliflozin 100mg was associated with greater reductions in SBP versus empagliflozin 10mg, pioglitazone, and sitagliptin (Δ–1.11 to –4.60) and provided comparable reductions in SBP versus dapagliflozin 10mg and empagliflozin 25mg (Δ0.65 and –0.31). CONCLUSIONS: The results of this NMA suggest that canagliflozin 300mg monotherapy was associated with consistently greater HbA1c and SBP reductions versus all comparators, relevant to UK prescribing habits; while canagliflozin 100mg was at least similar. Weight reductions were larger for both doses of canagliflozin compared to all comparators.