One-Year Treatment With Exenatide Improves β-Cell Function, Compared With Insulin Glargine, in Metformin-Treated Type 2 Diabetic Patients

A randomized, controlled trial

  1. Mathijs C. Bunck, MD1,
  2. Michaela Diamant, MD, PHD1,
  3. Anja Cornér, MD2,
  4. Bjorn Eliasson, MD, PHD3,
  5. Jaret L. Malloy, PHD4,
  6. Rimma M. Shaginian, MD5,
  7. Wei Deng, PHD4,
  8. David M. Kendall, MD4,6,
  9. Marja-Riitta Taskinen, MD, PHD2,
  10. Ulf Smith, MD, PHD, FRCP3,
  11. Hannele Yki-Järvinen, MD, PHD, FRCP2 and
  12. Robert J. Heine, MD, PHD, FRCP1,7
  1. 1Department of Endocrinology, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands;
  2. 2Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland;
  3. 3Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden;
  4. 4Amylin Pharmaceuticals, San Diego, California;
  5. 5Eli Lilly and Company, Houten, the Netherlands;
  6. 6International Diabetes Center, Minneapolis, Minnesota;
  7. 7Eli Lilly and Company, Indianapolis, Indiana.
  1. Corresponding author: Michaela Diamant, m.diamant{at}


OBJECTIVE Traditional blood glucose–lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in β-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp–derived measures of β-cell function, glycemic control, and body weight.

RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety.

RESULTS Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09–2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: −0.8 ± 0.1 and −0.7 ± 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference −4.6 kg, P < 0.0001). β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy.

CONCLUSIONS Exenatide significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, β-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.


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    • Received October 1, 2008.
    • Accepted January 19, 2009.
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  1. Diabetes Care vol. 32 no. 5 762-768
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