OBJECTIVES: To assess the relative efficacy of CANA, an inhibitor of sodium glucose co-transporter 2, versus GLP-1 agonists, in second and third line for the treatment of T2DM patients, using NMA. METHODS: A systematic review of randomized, controlled trials and Bayesian NMA were conducted to compare HbA1c lowering of CANA versus the GLP-1 agonists liraglutide and exenatide.  NMAs were conducted separately by background treatment (metformin or metformin plus sulfonylurea) and trial duration (26/52/104 weeks).  Networks were based on treatment- and dose-specific nodes.  Non-informative priors were used.  Relative efficacy was evaluated based on absolute differences in HbA1c reductions and Bayesian probabilities. RESULTS: In dual therapy, trials were identified reporting HbA1c reduction versus baseline at Weeks 26 (n=8), 52 (n=6), and 104 (n=2).  At Weeks 26 and 52, CANA 300/100mg had greater (Week 26: Δ=–0.17%/–0.28%) to similar (Week 52: Δ=–0.03%/0.09%) reductions versus exenatide 5µg, and lower/similar versus exenatide 10µg (Week 26: Δ=0.22%/0.10%).  Reductions were greater for liraglutide 1.8/1.2mg, with differences versus CANA ranging between 0.20% and 0.61%.  At 104 weeks, reductions were similar for CANA 100mg (Δ=0.04%/0.02%) and greater for CANA 300mg (Δ=0.13%/0.11%) compared to liraglutide 1.2/1.8mg.  In triple therapy, 5 trials reporting HbA1c reduction at Week 26 were identified to compare CANA versus liraglutide 1.8mg and exenatide 10/5µg.  Reductions for CANA 100mg were similar to exenatide 5µg (Δ=–0.02%) and lower versus exenatide 10µg and liraglutide 1.8mg (Δ=–0.24% and –0.33%, respectively).  Reductions for CANA 300mg were greater versus exenatide 5µg, and similar versus exenatide 10µg and liraglutide 1.8mg (Δ=–0.01% and 0.08%). CONCLUSIONS: NMA results for dual therapy suggest increasing relative efficacy of CANA over time versus GLP-1 agonists, with CANA 300mg reaching similar HbA1c reductions as GLP-1 agonists at 104 weeks.  NMA results for triple therapy suggest at least similar efficacy for CANA 300mg.