β-Cell Function and Glycemic Control Following One Year Exenatide Therapy, and after 12 Week Wash out, in Patients with Type 2 Diabetes
Abstract Number: 104-OR
Authors: MATHIJS C. BUNCK, MICHAELA DIAMANT, ANJA CORNER, BJORN ELIASSON, JARET L. MALLOY, RIMMA M. SHAGINIAN, WEI DING, DAVID M. KENDALL, MARJA-RITTA TASKINEN, ULF SMITH, HANNELE YKI-JARVINEN, ROBERT J. HEINE, Amsterdam, Netherlands, Helsinki, Finland, Göteborg, Sweden, San Diego, CA, Houten, Netherlands, Indianapolis, IN
Institutions: Indianapolis, IN; San Diego, CA
Results: Traditional blood glucose lowering agents do not sustain adequate glycemic control in most type 2 diabetic (T2D) patients. Both clinical and preclinical studies with the incretin mimetic exenatide show improvements in β-cell function. However, the effect of exenatide treatment on β-cell secretory function has not been evaluated. This study assessed the effect of 1 year of exenatide treatment (Ex; treat to A1C ≤ 7.0%; max dose 20 µg TID) vs. insulin glargine treatment (IG; treat to fasting plasma glucose <5.6 mmol/L) on β-cell function. A total of 69 metformin treated patients with T2D (mean±SD: age 58±8y; A1C 7.5±0.8%; BMI 31±4kg/m2) were randomized to Ex (n=36) or IG (n=33). β-cell function was measured during hyperglycemic (15 mM) clamp with arginine stimulation at baseline (week 0), after 52 weeks of Ex or IG therapy, and after a 4 week wash out. Both therapies reduced A1C similarly at 1 year ( -0.8±0.1%, and -0.7±0.2% for Ex and IG, respectively (P=0.55). During therapy, Ex significantly reduced body weight compared to IG (-3.6±0.6kg vs +1.0±0.8kg; P<0.0001). Arginine stimulated C peptide secretion during hyperglycemia was 146% greater (P<0.0001) after 52 weeks of Ex treatment (n=29) as compared to IG (n=30). In addition, improvements in 1st and 2nd phase glucose stimulated C-peptide secretion were 53% (P<0.0001) and 185% (P<0.0001) greater respectively with Ex vs. IG. After 4 week wash out from Ex or IG, all clamp derived β-cell function parameters were similar to pre treatment values. After 12 weeks of wash out, glycemia and weight trended towards pre treatment values in both groups. Adverse event rates were similar to previous exenatide trials. In conclusion, 1 year of Ex therapy significantly improved β-cell secretory function and reduced body weight as compared to IG therapy with similar improvements in glycemic control. Beneficial effects were not sustained following discontinuation of either 1-year treatment regimen. Longer duration of therapy may be required for disease modifying effects.