Unlike most other antihyperglycemic drugs, glucagon-like peptide 1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. In a randomized clinical trial (RCT) over 26 weeks reported by Buse et al. (2009), the novel GLP-1 agonist liraglutide (1.8mg once daily, OD) was found to be significantly more effective than exenatide (10μg twice daily) in terms of HBA1c reduction.  OBJECTIVES: To compare, from a German payer’s (SHI) perspective, the long-term clinical and cost effectiveness of liraglutide (1.8mg OD) versus exenatide (10μg BID) in T2D patients, based on data from the randomized clinical trial (RCT) by Buse et al., 2009.  METHODS: The CORE Diabetes Model (CDM) was applied using RCT data.  The model was calibrated to RCT baseline characteristics and background mortality in a German diabetes population, applying epidemiological data from long-term studies including UKPDS and Framingham to project morbidity and mortality of T2DM.  Unit costs for direct costs were applied from an SHI perspective for year 2009. A discounting rate of 3% was used for costs and clinical effects. For hypothetical cohorts of 1000 patients, each followed for 20 years, patients were assumed to be maintained on liraglutide and exenatide, respectively, for 5 years and subsequently switched to insulin.  Costs and effects were projected over a 20-year time horizon.   RESULTS: Estimated 20-year survival rates were higher for liraglutide 1.8mg once daily (36.8%) compared to exenatide 10μg administered twice daily (35.6%), and cumulative costs were €46,308 (liraglutide) and €45,025 (exenatide), respectively.  Base case ICERs were €16,632 per life year gained for liraglutide versus exenatide, and €11,606 for liraglutide versus exenatide per QALY gained.  Sensitivity analyses indicated robustness of findings.   CONCLUSIONS: Long-term projections combining RCT data with the CDM strongly suggest an acceptable to attractive cost effectiveness of liraglutide compared to exenatide according to currently prevailing standards.