Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

Abstract

Background: The once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes.

Methods: A 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years.

Results: In the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer population. Nausea (predominantly mild in intensity) was the most common adverse event, although the frequency and intensity of nausea decreased over time. No severe hypoglycemia was observed.

Conclusions: Exenatide QW was well tolerated during the 2-year treatment period. This study demonstrated sustained glucose control and weight loss throughout 2 years of treatment with exenatide QW.

Trial registration: ClinicalTrials.gov NCT00308139.

Figures

Figure 1

Enrollment, patient disposition, and baseline characteristics. Of the 303 patients originally randomized to the study, 295 comprised the ITT population and 258 entered the subsequent 74-week assessment period (ITT population). Forty-two patients withdrew during the 74-week open-ended assessment period, resulting in a completer population of n = 216. The disposition and demographic characteristics of the 30-week and 52-week populations have been published previously [25,26].

Figure 2

Improvements in glycemic control over 104 weeks in the completer population (N = 216) and intent-to-treat population (N = 295). A) LS mean ± SE changes in A1C over 104 weeks. Baseline (BL) was 8.2% in the 2-year completer population and 8.3% in the ITT population. B) Proportion of patients who achieved A1C targets of <7.0%, ≤6.5%, and ≤6.0%. C) LS mean ± SE changes in fasting plasma glucose over 104 weeks. Baseline was 168 mg/dL in the 2-year completer population and 169 mg/dL in the ITT population.

Figure 3

Improvements in body weight, blood pressure, and serum lipids. A) LS mean ± SE changes in body weight at 2 years for the ITT (N = 295) and completer populations (N = 216). B) Reductions in both body weight and A1C in the completer population after 104 weeks. C) LS mean change from baseline ± SE in systolic blood pressure (SBP) after 104 weeks of treatment, further analyzed by normal or abnormal baseline SBP, in the completer population (N = 216; Normal baseline, n = 113; Abnormal baseline, n = 103) and ITT population (All, N = 295; Normal baseline, n = 158; Abnormal baseline, n = 137). D) Changes in serum lipids were seen at week 104 (completer and IIT populations): data are presented as LS mean ± SE for all lipids except for triglycerides (geometric LS mean percent change ± SE from baseline).