DURATION-5: Exenatide Once Weekly Resulted in Greater Improvements in Glycemic Control Compared with Exenatide Twice Daily in Patients with Type 2 Diabetes

Context: We wanted to understand the effects of once-weekly vs. twice-daily glucagon-like peptide-1 receptor agonism for treatment of patients with type 2 diabetes. Objective: The objective of the study was to compare effects of exenatide once weekly (ExQW) and exenatide twice daily (ExBID) on glycemic control, body weight, and safety. Design: This was a 24-wk, randomized, open-label, comparator-controlled study. Setting: The study was conducted at 43 sites in the United States. Patients: The study population was 252 intent-to-treat patients with type 2 diabetes [baseline (mean +/- SD): glycosylated hemoglobin (HbA1c) 8.4 +/- 1.2%, fasting plasma glucose 171 +/- 47 mg/dl, weight 96 +/- 20 kg] that were drug naive (19%) or previously treated with one (47%) or multiple (35%) oral antidiabetic medications. Interventions: Interventions included ExQW 2 mg for 24 wk or ExBID 5 mu g for 4 wk followed by ExBID 10 mu g for 20 wk. Main Outcome Measure: The change in HbA1c from baseline to wk 24 was measured. Results: At 24 wk, ExQW produced significantly greater changes from baseline (least squares mean +/- SE) vs. ExBID in HbA1c (-1.6 +/- 0.1% vs. -0.9 +/- 0.1%; P < 0.0001) and fasting plasma glucose (-35 +/- 5 mg/dl vs. -12 +/- 5 mg/dl; P = 0.0008). Similar reductions in mean body weight from baseline to wk 24 were observed in both groups (-2.3 +/- 0.4 kg and -1.4 +/- 0.4 kg). Both treatments were generally well tolerated. Transient and predominantly mild to moderate nausea, the most frequent adverse event, was less common with ExQW (14%) than with ExBID (35%). Injection-site reactions were infrequent, but more common with ExQW. No major hypoglycemia occurred. Conclusions: Continuous glucagon-like peptide-1 receptor agonism with ExQW resulted in superior glycemic control, with less nausea, compared with ExBID in patients with type 2 diabetes. Both groups lost weight. (J Clin Endocrinol Metab 96: 1301-1310, 2011)