Effects of exenatide and liraglutide on postchallenge glucose disposal in individuals with normal glucose tolerance.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are categorized as short- or long-acting types, but information regarding differences in the effects of these two types on postprandial glucose disposal has been limited. We have now investigated the effects of exenatide and liraglutide (short- and long-acting GLP-1RAs, respectively) on glucose disposal during an oral glucose tolerance test (OGTT). Fourteen healthy volunteers with normal glucose tolerance underwent three OGTTs, which were performed without pharmacological intervention or after a single administration of exenatide or liraglutide at 30 min and 10 h, respectively, before test initiation. The three OGTTs were performed with intervals of at least 7 days between successive tests and within a period of 2 months. Exenatide, but not liraglutide, markedly decelerated the peak of both plasma glucose and serum insulin levels during the OGTT, with the peaks of both glucose and insulin concentrations occurring at 150 min after test initiation with exenatide compared with 30 min in the control condition or with liraglutide. Exenatide and liraglutide reduced the area under the curve for plasma glucose levels during the OGTT by similar extents, whereas that for serum insulin levels was reduced only by exenatide. Our results suggest that exenatide decelerates the increase in plasma glucose levels through inhibition of glucose absorption and that it exerts an insulin-sparing action after glucose challenge.