DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks

Abstract

Objective: In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks.

Research design and methods: In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID-->QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed.

Results: Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean -2.0% [95% CI -2.1 to -1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C <7.0% and <or=6.5%, respectively. In both treatment arms, FPG was reduced by >40 mg/dl, and body weight was reduced by >4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed.

Conclusion: Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss.

Trial registration: ClinicalTrials.gov NCT00308139.

Figures

Figure 1

Enrollment, patient disposition, and baseline characteristics. Of the 303 patients originally randomized to the study, 258 entered the subsequent 22-week assessment period. Fifteen patients withdrew during the 22-week assessment period, resulting in an evaluable population of n = 241 (n = 120 QW only; n = 121 BID→QW). Demographics of the ITT population are available in Drucker et al. (17) and represent the information at the original baseline. MET, metformin; SFU, sulfonylurea; TZD, thiazolidinedione.

Figure 2

Glycemic control and body weight over 52 weeks. A: Least squares mean ± SE changes in A1C over 52 weeks for the evaluable population (exenatide QW-only n = 120; exenatide BID→exenatide QW n = 121). B: Least squares mean ± SE change in A1C for ITT (n = 148) and evaluable population patients receiving only exenatide QW for 52 weeks. C: Change in fasting plasma glucose over 52 weeks for the evaluable population. D: Proportion of patients achieving A1C targets of <7.0, ≤6.5, and ≤6.0%. E: Least squares mean ± SE changes in body weight over 52 weeks for the evaluable population. F: Scatterplot of change in A1C vs. change in body weight. *P < 0.05 versus exenatide BID→exenatide QW. BL, baseline.

Figure 3

Change from baseline in blood pressure and serum lipids. A: Patients (ITT population) in both treatment groups exhibited favorable changes (least squares mean change from baseline ± SE) in blood pressure after 52 weeks of treatment. B: Treatment with exenatide QW was associated with favorable changes in serum lipids (evaluable population). Data are presented as least squares mean ± SE for all lipids except for triglycerides (geometric least squares mean milligrams per deciliter baseline; geometric least squares mean percent change ± SE from baseline). ITT population: exenatide QW-only n = 148; exenatide BID→exenatide QW n = 147. Evaluable population: exenatide QW-only n = 120; exenatide BID→exenatide QW n = 121. BL, baseline.