Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

David C. Klonoff, John B. Buse, Loretta L. Nielsen, Xuesong Guan, Christopher Bowlus, John H. Holcombe, Matthew E. Wintle, David G. Maggs

Research output: Contribution to journalArticlepeer-review

659 Scopus citations


Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of ≥ 3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety. Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5 μg exenatide, or 10 μg exenatide for 30 weeks, followed by 5 μg exenatide BID for 4 weeks, then 10 μg exenatide BID for ≥ 3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas. Results: 217 patients (64% male, age 58 ± 10 years, weight 99 ± 18 kg, BMI 34 ± 5 kg/m2, A1C 8.2 ± 1.0% [mean ± SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (-1.1 ± 0.1% [mean ± SEM]) were sustained to 3 years (-1.0 ± 0.1%; p < 0.0001), with 46% achieving A1C ≤ 7%. Exenatide progressively reduced body weight from baseline (-5.3 ± 0.4 kg at 3 years; p < 0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n = 116) had reduced ALT (-10.4 ± 1.5 IU/L; p < 0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (-6.1 ± 0.6 kg vs. -4.4 ± 0.5 kg; p = 0.03), however weight change was minimally correlated with baseline ALT (r = -0.01) or ALT change (r = 0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n = 151). Triglycerides decreased 12% (p = 0.0003), total cholesterol decreased 5% (p = 0.0007), LDL-C decreased 6% (p < 0.0001), and HDL-C increased 24% (p < 0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison. Conclusion: Adjunctive exenatide treatment for ≥ 3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.

Original languageEnglish (US)
Pages (from-to)275-286
Number of pages12
JournalCurrent Medical Research and Opinion
Issue number1
StatePublished - Jan 2008


  • ALT
  • AST
  • Exenatide
  • Exendin-4
  • HDLC
  • Incretin mimetic
  • LDL-C
  • Triglycerides
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine(all)


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