Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Background: Long-term treatment is necessary to slow the progression of type 2 diabetes (T2D). Here, we examined the safety and efficacy of 6 years of treatment with exenatide once weekly (QW) among patients with T2D in the DURATION-1 trial. Methods: The study enrolled patients aged >= 16 years with T2D treated primarily with metformin and sulfonylureas. Following 30 weeks of randomized treatment with exenatide QW 2mg or exenatide twice daily 10 mu g, patients entered an uncontrolled, open-label, open-ended study phase in which all patients received exenatide QW 2 mg. Restrictions on concomitant medication use were eased over time. Results: Of the original 295 patients in the intent-to-treat population, 136 (46%) completed 6 years of treatment. Six-year completers had sustained significant improvements from baseline in glycated hemoglobin (HbA1c; least-squares mean [LSM] change, -1.6%), with 46.3% achieving HbA1c <7.0%, 33.1% achieving HbA1c <= 6.5%, and significant improvements from baseline in fasting plasma glucose (-28 mg/dL) and body weight (-4.2 kg) at 6 years. The 78 completers who added no glucose-lowering medications had numerically greater body weight reductions than the overall cohort (6-year LSM change, -6.1 kg) with more stability over time. No unexpected adverse events were observed during 1202.4 patient-years of exposure. Most minor hypoglycemia events occurred with concomitant sulfonylurea use. Conclusions: Exenatide QW was associated with clinically significant, sustained improvements in glycemic control and weight in patients who continued therapy for up to 6 years, without unexpected safety findings. ClinicalTrials.gov registration: NCT00308139.