OBJECTIVES: A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide 2mg once-weekly (EQW), a glucagon-like peptide-1 receptor agonist (GLP-1 RA), compared to other GLP-1 RAs for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin (MET). METHODS: A systematic literature review was conducted. Randomised controlled trials (RCTs) were of 24 weeks (± 6 weeks) treatment duration. Bayesian fixed-effect (FE) and random-effects (RE) models were used to estimate the relative efficacy and tolerability, and 95% credible intervals (CrIs). RESULTS: Fourteen RCTs were included. The RE model was selected a prioriover the FE model. The FE model did not provide a better fit to the data, based on the deviance information criterion. EQW was statistically significantly better than placebo (mean; 95% CrI) (-1.09%; -1.62% to -0.53%) in reducing HbA1c. EQW obtained a statistically significant reduction in HbA1c relative to lixisenatide 20ug QD. Favourable point estimates that did not reach statistical significance were observed for EQW vs. albiglutide 30mg QW, exenatide 5ug and 10ug twice daily (BID), and liraglutide 1.2mg and 1.8mg once daily (QD). A model adjusting for baseline HbA1c did not provide a better fit to the data than the unadjusted model. EQW was associated with a lower risk of nausea compared to all GLP-1 RAs, except exenatide 5ug BID (none of these differences were statistically significant). Risk of discontinuation due to adverse events was lower for EQW than for dulaglutide 1.5mg QW, and liraglutide 1.2mg and 1.8mg QD, and higher for EQW than for lixisenatide 20ug QD and exenatide 5ug and 10ug BID (none of these differences were statistically significant). CONCLUSIONS: Evidence suggests that EQW is an effective, well-tolerated therapeutic option for the treatment of T2DM in adults inadequately controlled on MET alone.