Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes

Objectives: To evaluate the effect of exenatide on gastric emptying (GE) in type 2 diabetes using scintigraphy. Methods: Seventeen subjects with type 2 diabetes participated in a randomized, single-blind, 3-period. crossover study. In each 5-day period, 5 or 10 mu g exenatide or placebo was administered subcutaneously BID. Oral antidiabetic treatments were continued. The presence of cardiac autonomic neuropathy was assessed during screening. On day 5. after the morning dose, subjects consumed a 450-kcal breakfast containing Tc-99m-labeled eggs and In-m-labeled water, and GE was measured by scintigraphy. Plasma glucose and insulin, perceptions of appetite, and plasma exenatide were also quantified. Results: Exenatide slowed GE of both solid and liquid meal components [solid (T-50(90% confidence interval [CI]); placebo, 60(50-70) min; 5 mu g exenatide. 111(94-132) min; 10 mu g exenatide, 169(143-201) min; both P<0.01); liquid (T-50(90% CI), placebo, 34(25-46) min; 5 mu g exenatide, 87(65-117) min; 10 mu g exenatide, 114(85-154) min; both P<0.01)]. GE was not different between subjects with cardiac autonomic neuropathy (n=7), compared with those without (n=10) (P >= 0.68). Exenatide reduced postprandial glucose (area under the curve [AUC((0-6 h))]) by 69-76% and peak insulin (C-max) by 84-86% compared with placebo. There was an inverse relationship between the postprandial rise in glucose (AUC(0-3 h) and GE (solid T-50, r=-0.49, P<0.001). Conclusions: Exenatide slows GE substantially in type 2 diabetes, which could be an important mechanism contributing to the beneficial effect of exenatide on postprandial glycemia. (C) 2008 Elsevier B.V. All rights reserved.