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.

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.

This was a 24-wk, randomized, open-label, comparator-controlled study.

The study was conducted at 43 sites in the United States.

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 naïve (19%) or previously treated with one (47%) or multiple (35%) oral antidiabetic medications.

Interventions included ExQW 2 mg for 24 wk or ExBID 5 μg for 4 wk followed by ExBID 10 μg for 20 wk.

The change in HbA1c from baseline to wk 24 was measured.

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.

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.