OBJECTIVES: In clinical trials, exenatide improved glycaemic control and was associated with weight reduction and improvement in several cardiovascular risk factors. In this retrospective analysis using a large, national commercial health care claims database, we describe changes in concomitant diabetes therapies in patients with type 2 diabetes who had a prescription claim for exenatide in the first 13 months following US FDA approval. METHODS: A total of 1637 patients who were at least 18 years old, had type 2 diabetes, had an initial (index) claim for exenatide between May 1, 2005 and May 31, 2006, and had 12 months of pre index and 6 months of post index eligibility were included. Baseline diabetes therapies were defined as prescriptions filled 100 days pre index through 15 days post index; post-index therapies were defined as any prescriptions filled at least 16 days to 180 days post index. RESULTS: In the post-index period, the number of patients with prescription claims for metformin, thiazolidinediones, and sulphonylureas decreased by 14.3% (P<0.0001), 16.0% (P<0.0001), and 25.0% (P<0.0001), respectively. Patients with prescription claims for both metformin and a sulphonylurea declined by 25.9% (P<0.0001) and patients with prescriptions claims for the combination of metformin, a thiazolidinedione, and a sulphonylurea decreased by 40.1% (P<0.0001). The percentage of patients with prescription claims for insulin was similar between baseline and post-index periods. CONCLUSION: This study provides the first nonclinical trial population analysis of changes in concomitant diabetes therapies following initiation of exenatide therapy, and demonstrates that exenatide initiation was associated with a significant reduction in prescription claims for other diabetes therapies.