Purpose. The case of a patient with type 2 diabetes mellitus who received combination exenatide-sitagliptin with glipizide is reported. Summary. A 55-year-old, 204-lb Caucasian woman arrived at a clinic with polydipsia. Her blood glucose concentration was 450 mg/dL and her glycosylated hemoglobin (HbA(1c)) value was 13.4%. She was diagnosed with type 2 diabetes mellitus and started on metformin hydrochloride 500 mg orally twice daily. Metformin was later discontinued due to elevated liver function test values. Sitagliptin 100 mg daily was substituted, and glipizide was later added and its dosage adjusted over the next several months. After six months, her HbA(1c) value had decreased to 9.3% and she had gained 14 lb. Exenatide was then added to her regimen, and the dosage was adjusted to 10 mu g subcutaneously twice daily. Two months after the initiation of sitagliptin, glipizide, and exenatide, the patient had lost 10 lb, reported significant improvements in self-monitored blood glucose readings, and required a reduction in glipizide dosage despite no reported therapeutic lifestyle changes. Seven months after the initiation of exenatide, sitagliptin, and glipizide, her HbA(1c) value was 7.4%. Triple therapy resulted in a total HbA(1c) value reduction of 1.9%, a weight loss of 11 lb, and normalized liver function test values. The patient's high blood pressure was treated with losartan and remained at goal throughout the duration of this report. Conclusion. In a patient with type 2 diabetes mellitus, the addition of the incretin mimetic exenatide and the dipeptidyl peptidase-4 inhibitor sitagliptin to glipizide therapy appeared effective and safe. Am J Health-Syst Pharm. 2012; 69:1044-8