OBJECTIVES: To compare healthcare costs between type 2 diabetes mellitus (T2DM) patients newly initiating exenatide once weekly (exenatide QW), exenatide twice daily (exenatide), or liraglutide (LIRA). METHODS: This administrative claims-based retrospective cohort study included patients if they had T2DM, were GLP-1RA-naïve, initiated a GLP-1RA between 2/1/2012-6/30/2012 (initiation date=index), were aged ≥18 years, and had continuous enrollment for 12 months before (baseline) to 6 months after index (follow-up). Outcomes included healthcare costs (Total/Diabetes-related/GLP-1RAs) and hospitalizations (Total/Diabetes-related). Diabetes-related outcomes included those associated with antidiabetes medications and medical claims coded with T2DM ICD-9-CM codes. Outcomes were compared between index GLP-1RAs using multivariable generalized linear models. Pre-specified sensitivity analyses were performed stratifying by LIRA 1.2mg and LIRA 1.8mg and among patients with ≥60 days’ supply of their index GLP-1RA within ≤67 days after index (initial adherers). RESULTS: The study sample included 1,610 exenatide QW, 2,690 exenatide, and 6,499 LIRA patients. In multivariable-adjusted models, healthcare costs varied widely across GLP-1RAs and analyses, with exenatide generally being associated with the lowest adjusted healthcare costs (cost ratios vs. exenatide QW ranging from 0.762 [p<0.001] for GLP-1RA costs to 0.908 [p<0.001] for Total costs among initial adherers). LIRA 1.8mg was generally associated with the highest adjusted healthcare costs (cost ratios vs. exenatide QW ranging from 1.039 [p=0.080] for Total costs to 1.157 [p<0.001] for GLP-1RA costs among initial adherers). LIRA 1.2mg was generally associated with the highest adjusted odds of hospitalizations (odds ratios vs. exenatide QW ranging from 1.312 [p=0.317] for diabetes-related hospitalizations to 1.528 [p<0.036] for total hospitalizations among initial adherers). CONCLUSIONS: Among patients newly initiating exenatide QW, exenatide, or LIRA, differences existed in healthcare costs and hospitalization in first 6 months of treatment. LIRA 1.8mg and 1.2mg were generally associated with the highest adjusted healthcare costs and odds of hospitalization, respectively.