One-year Treatment With Exenatide Improves β-Cell Function, Compared With Insulin Glargine, in Metformin-Treated Type 2 Diabetic Patients A randomized, controlled trial

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 P-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 P-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). beta-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% Cl 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). P-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 P-cell function during I year of treatment compared With titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, R-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.