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

ObjectivesTo evaluate the effect of exenatide on gastric emptying (GE) in type 2 diabetes using scintigraphy.MethodsSeventeen subjects with type 2 diabetes participated in a randomized, single-blind, 3-period, crossover study. In each 5-day period, 5 or 10 microg 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 (99m)Tc-labeled eggs and (111)In-labeled water, and GE was measured by scintigraphy. Plasma glucose and insulin, perceptions of appetite, and plasma exenatide were also quantified.ResultsExenatide slowed GE of both solid and liquid meal components [solid (T(50)(90% confidence interval [CI]); placebo, 60(50-70) min; 5 microg exenatide, 111(94-132) min; 10 microg exenatide, 169(143-201) min; both 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, PConclusionsExenatide slows GE substantially in type 2 diabetes, which could be an important mechanism contributing to the beneficial effect of exenatide on postprandial glycemia.Helle Linnebjerg, Soomin Park, Prajakti A. Kothare, Michael E. Trautmann, Kenneth Mace, Mark Fineman, Ian Wilding, Michael Nauck and Michael Horowit