Abstract

Background: Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported. Objective: To compare the effects of exenatide versus placebo on glycemic control. Design: Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005. Setting: 49 sites in Canada, Spain, and the United States. Patients: 233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean (±SE) baseline glycated hemoglobin A1c level was 7.9% ± 0.1%. Interventions: Subcutaneous abdominal injections of 10 µg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks. Measurements: The primary outcome was change from baseline in hemoglobin A1c level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events. Results: Exenatide treatment reduced hemoglobin A1c level (mean difference, −0.98% [95% CI, −1.21% to −0.74%]), serum fasting glucose level (mean difference, −1.69 mmol/L [−30.5 mg/dL] [CI, −2.22 to −1.17 mmol/L {−40.0 to −21.1 mg/dL}]), and body weight (mean difference, −1.51 kg [CI, −2.15 to −0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia. Limitations: Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study. Conclusions: Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy. ClinicalTrials.gov registration number: NCT00099320.