The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes

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 microg 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 A (1c) 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. For more information on exenatide click here.