The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial.

<bold>Background: </bold>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.<bold>Objective: </bold>To compare the effects of exenatide versus placebo on glycemic control.<bold>Design: </bold>Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005.<bold>Setting: </bold>49 sites in Canada, Spain, and the United States.<bold>Patients: </bold>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%.<bold>Interventions: </bold>Subcutaneous abdominal injections of 10 microg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks.<bold>Measurements: </bold>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.<bold>Results: </bold>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.<bold>Limitations: </bold>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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]