OBJECTIVES: Two recent multicenter, comparator-controlled, open-label, randomized, parallel group clinical trials comparing exenatide with insulin glargine and with biphasic insulin aspart provided evidence of the short-term clinical profile of exenatide. The objective of this cost-effectiveness analysis was to use these results as the basis for long-term projections to estimate the clinical and economic outcomes associated with exenatide treatment versus insulin glargine and versus biphasic insulin aspart in Portuguese health care setting. METHODS: The previously published and validated IMS Core Diabetes Model was used to project the long-term clinical and cost outcomes for a cohort defined as the intention-to-treat (ITT) population of patients in the H8O-MC-GWAA and H8O-MC-GWAD clinical trials having a baseline BMI ≥ 35 kg/m2. Portuguese-specific direct medical costs data were used in the analysis to model outcomes over a 35-year time horizon from the National Health Service perspective. RESULTS: Exenatide was associated with ICERs of €61,637 per life year gained and €17,222 per QALY gained versus biphasic insulin aspart. Exenatide was also associated with ICERs of €53,275 per life year gained and €14,697 per QALY gained versus insulin glargine from the National Health Service perspective. Results from 18 sensitivity analyses and two BMI subgroup analyses indicated a limited impact of baseline BMI on the final results. Results were sensitive to disutilities applied for excess BMI and nausea. Results were also sensitive to assumed insulin daily doses (IU) for insulin glargine and biphasic insulin aspart after the first year. CONCLUSIONS: The outcomes of this CEA and CUA were that exenatide has been projected to improve life expectancy and quality-adjusted life expectancy compared to both insulin glargine and to biphasic insulin aspart in patients with type 2 diabetes failing OADs. Based upon these results exenatide could be considered good value for money in Portugal regardless of baseline BMI levels.