Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study

Summary

Background

Exenatide is an incretin mimetic that shares glucoregulatory properties with glucagon-like peptide 1 (GLP-1), and improves glycaemic control, with progressive bodyweight reductions, when administered twice a day in patients with type 2 diabetes. We compared the efficacy of a once-weekly formulation of exenatide to that of a twice daily dose.

Methods

A 30-week, randomised, non-inferiority study compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 μg exenatide administered twice a day, in 295 patients with type 2 diabetes (haemoglobin A_1c [HbA_1c] 8·3% [SD 1·0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6·7 [SD 5·0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA_1c at 30 weeks. This study is registered with ClinicalTrials.gov, number NCT00308139.

Findings

At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA_1c than those given exenatide twice a day (−1·9 [SE 0·1%] vs −1·5 [0·1%], 95% CI −0·54% to −0·12%; p=0·0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA_1c levels of 7·0% or less (77% vs 61% of evaluable patients, p=0·0039).

Interpretation

Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight.

Funding

Amylin Pharmaceuticals Inc and Eli Lilly and Company.