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

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• 作者：Kristin Taylor (1)
  Kate Gurney (1)
  Jenny Han (1)
  Richard Pencek (1)
  Brandon Walsh (1)
  Michael Trautmann (2)
  
• 刊名：BMC Endocrine Disorders
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：11
• 期：1
• 全文大小：638KB
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  37. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6823/11/9/prepub
  
• 作者单位：Kristin Taylor (1)
  Kate Gurney (1)
  Jenny Han (1)
  Richard Pencek (1)
  Brandon Walsh (1)
  Michael Trautmann (2)
  
  1. Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA, 92121, USA
  2. Eli Lilly and Company, Lilly Corporate Center: DC 6038, Indianapolis, IN, 46285, USA
  

文摘

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 ?.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