OBJECTIVES: A once-weekly formulation of exenatide (EQW) received positive opinion from the EMA in April 2011 for the treatment of type 2 diabetes.  No head-to-head study of EQW and liraglutide 1.2mg once-daily (the dose recommended by NICE) has been conducted therefore a network meta-analysis to compare EQW to liraglutide 1.2mg in terms of effect on HbA1c was performed.  METHODS: A systematic review was conducted to identify randomized controlled trials of EQW and liraglutide (1.2mg and 1.8mg) of 24 weeks or more, and the common comparators insulin glargine and exenatide bid to allow a network meta-analysis.  Additionally, the manufacturing companies were asked to provide any unpublished data from studies meeting the criteria. 22 studies including 10,816 patients met our inclusion criteria.   Treatments were compared in terms of mean difference in HbA1c relative to placebo. Additionally, EQW was compared to both doses of liraglutide, and liraglutide 1.2mg was compared to liraglutide 1.8mg. RESULTS: Results from random effects models controlling for baseline HbA1c are presented.  Analysis of change in HbA1c produced estimated mean differences relative to placebo of -1.15% (95% CI -1.31, -1.00) for EQW, -1.01% (95% CI -1.18, -0.85) for liraglutide 1.2mg, and -1.18% (95% CI -1.32%, -1.04%) for liraglutide 1.8mg.  The comparison of EQW to liraglutide 1.2mg and liraglutide 1.8mg showed a mean difference (95% CI) of -0.14% (-0.34, 0.06) and 0.03% (-0.14, 0.18) respectively. Liraglutide 1.2mg compared to liraglutide 1.8mg showed a mean difference in HbA1c of 0.17% (0.02, 0.30). Results were consistent when controlling for use of background antihyperglyemic medications.  CONCLUSIONS: Our analysis suggests EQW and both doses of liraglutide have robust and similar efficacy with respect to lowering of HbA1c.  Further analysis is warranted to investigate the inconsistency between the direct and indirect evidence with respect to the comparison of EQW to liraglutide 1.8mg.