One-Year Treatment With Exenatide Improves Beta-Cell Function, Compared To Insulin Glargine, In Metformin Treated Type 2 Diabetes Patients: A Randomized, Controlled Trial
- Mathijs C. Bunck, MDa,
- Michaela Diamant, MD, PhD (m.diamant{at}vumc.nl)a,
- Anja Cornér, MDb,
- Bjorn Eliasson, MD, PhDc,
- Jaret L. Malloy, PhDd,
- Rimma M. Shaginian, MDe,
- Wei Deng, PhDd,
- David M. Kendall, MDd,f,
- Marja-Riitta Taskinen, MD, PhDb,
- Ulf Smith, MD, PhD, FRCPc,
- Hannele Yki-Järvinen, MD, PhD, FRCPb and
- Robert J. Heine, MD, PhD, FRCPa,g
- aDepartment of Endocrinology, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands
- bDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- cLundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Goteborg, Sweden
- dAmylin Pharmaceuticals, Inc., San Diego, CA, United States
- eEli Lilly and Company, Houten, the Netherlands
- fInternational Diabetes Center, Minneapolis, MN, United States
- gEli Lilly and Company, Indianapolis, IN, United States
Abstract
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 beta-cell function. We investigated the effects of 52-weeks treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp derived measures of beta-cell function, glycemic control and body weight.
Research Design and Methods: Sixty-nine metformin-treated patients with type 2 diabetes were randomized to exenatide (n=36) or insulin glargine (n=33). Beta-cell function was measured during an arginine stimulated hyperglycemic clamp at week 0, week 52 and after a 4-week off-drug period. Additional endpoints 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 to 2.90, p<0.0001] greater following 52-week exenatide treatment as compared to insulin glargine. Both exenatide and insulin glargine reduced hemoglobin (Hb) A1C similarly: −0.8±0.1% and −0.7±0.2% respectively (P=0.55). Exenatide reduced body weight compared to insulin glargine (difference −4.6 kg, p<0.0001). Beta-cell function measures returned to pre-treatment values in both groups after 4-week off-drug. HbA1c and body weight rose to pre-treatment values 12-weeks after discontinuing either exenatide or insulin glargine therapy.
Conclusions: Exenatide significantly improves beta-cell function during 1-year of treatment as compared to titrated insulin glargine. Following cessation of both exenatide and insulin glargine therapy beta-cell function and glycemic control returned to pre-treatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
Footnotes
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- Received October 1, 2008.
- Accepted January 19, 2009.
- Copyright © American Diabetes Association
