One-Year Treatment With Exenatide Improves Beta-Cell Function, Compared To Insulin Glargine, In Metformin Treated Type 2 Diabetes Patients: A Randomized, Controlled Trial.

Author(s): Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ

Affiliation(s): Department of Endocrinology, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands.

Publication date & source: 2009-02-05, Diabetes Care., [Epub ahead of print]

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) A(1C) 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. HbA(1c) 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.