OBJECTIVES: This study compares the effect of two injectable therapies, exenatide and insulin glargine, on quality of life measurements in patients with type 2 diabetes inadequately controlled on oral antidiabetic medications. Previous research has shown that increasing treatment complexity results in a negative impact on patient reported outcomes. As exenatide and insulin glargine are both adjunctive to pre-existing oral therapy in this study, the impact on quality of life from adding an injectable therapy is examined. Additionally, differences in quality of life between the medications are examined. METHODS: Patients were randomized to either twice daily exenatide (N=228) or once daily glargine (N=227) during the 26-week, non-inferiority trial. The Vitality Scale of the Short Form 36, The Diabetes Symptom Checklist – Revised, The EuroQol instrument (EQ-5D), The Treatment Flexibility Scale, and The Diabetes Treatment Satisfaction Questionnaire (DTSQ) were administered at baseline and endpoint. Change from baseline to endpoint was compared within each treatment, and then between treatment groups with analysis of covariance models, controlling for country and baseline scores. RESULTS: At endpoint, exenatide and glargine achieved similar HbA1c reductions. In each patient reported outcome instrument, both treatment groups improved from baseline to endpoint; however no statistically significant differences were observed between the treatment groups. Because exenatide was associated with a higher incidence of nausea, the impact of treatment satisfaction, as measured by the DTSQ, was assessed for those exenatide patients who experienced nausea during the trial (n=126). These patients demonstrated improvement from baseline to endpoint as well. CONCLUSION: Both injectable medications significantly improved the quality of life when added to pre-existing oral therapy. Exenatide, injected twice daily, was associated with an elevated incidence of nausea. However, despite the addition of an injection requirement and side effect of nausea, treatment satisfaction in exenitide group was comparable to that of the glargine group.