Efficacy, Safety, and Tolerability of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus: An Integrated Analysis of the DURATION Trials

Abstract

Background and Aim: Exenatide is a glucagon-like peptide-1 receptor agonist demonstrated to improve glycemic control with low hypoglycemia risk in patients with type 2 diabetes mellitus. The Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly (DURATION) program comprised 6 randomized, comparator-controlled, 24- to 30-week trials of exenatide once weekly (EQW), an extended-release formulation. This post hoc analysis pooled data from patients taking EQW across 6 trials to assess efficacy and safety in a large, varied patient population. Materials and Methods: The intent-to-treat (ITT) population contained 1379 patients (baseline mean ± standard deviation glycated hemoglobin [HbA_1c] levels of 8.4% ± 1.1%) who were treated with EQW over the course of 24 to 30 weeks. Changes from baseline in efficacy parameters for the ITT population and a completer population (1195 patients with ≥ 22 weeks of exposure) were evaluated. Results: The ITT population experienced significant reductions from baseline (least-squares mean [95% CI]) in HbA_1c levels (−1.4% [−1.5% to −1.4%]), fasting blood glucose levels (−36 mg/dL [−38.4 mg/dL to −33.8 mg/dL]), and body weight (−2.5 kg [−2.8 kg to −2.3 kg]) after 24 to 30 weeks of EQW treatment. Reductions in HbA_1c and fasting blood glucose levels were observed across baseline HbA_1c, level strata; patients with higher baseline HbA_1c levels experienced greater reductions. Treatment with EQW was associated with modest, significant reductions in blood pressure (systolic blood pressure, −2.8 mm Hg [−3.5 mm Hg to −2.1 mm Hg]; diastolic blood pressure, −0.8 mm Hg [−1.2 mm Hg to −0.4 mm Hg]), and fasting lipid levels (total cholesterol, −6.5 mg/dL [−8.2 mg/dL to −4.7 mg/dL]; low-density lipoprotein cholesterol, −3.9 mg/dL [5.3 mg/dL to −2.5 mg/dL]; and triglyceride [geometric least-squares mean percent change (95% CI)], −6% [−8% to −4%] levels). Similar reductions were observed in the completer population. Exenatide once weekly was generally well tolerated. Transient, mild-to-moderate gastrointestinal treatment-emergent adverse events and injection-site treatment-emergent adverse events were reported most frequently, but were seldom treatment limiting. No major hypoglycemic events were observed; minor hypoglycemic events occurred infrequently in patients not using a sulfonylurea. Conclusion: This post hoc analysis of > 1300 patients demonstrated that EQW was associated with significant reductions in HbA_1c levels, body weight, blood pressure, and fasting lipid levels, with minimal hypoglycemia risk. Consistent with established safety profiles, EQW therapy was generally well tolerated., Trial registration: www.ClinicalTrials.gov identifiers: NCT00308139, NCT00637273, NCT00641056, NCT00676338, NCT00877890, NCT01029886

• GLP-1 receptor agonist
• exenatide once weekly
• DURATION trials
• type 2 diabetes mellitus