Role of endogenous glucagon-like peptide-1 enhanced by vildagliptin in the glycaemic and energy expenditure responses to intraduodenal fat infusion in type 2 diabetes

Abstract

AIMS:Dipeptidyl peptidase-4 (DPP-4) inhibitors prolong the action of endogenous glucagon-like peptide-1 (GLP-1), the secretion of which is influenced by dietary macronutrients, particularly fat. In health, the DPP-4 inhibitor, vildagliptin, has been shown to lower blood glucose and glucagon and increase energy expenditure during an intraduodenal fat infusion. We evaluated the effects of vildagliptin on these responses, and the contribution of endogenous GLP-1-signalling in type 2 diabetes (T2DM). METHODS:15 T2DM patients, managed by diet and/or metformin (HbA1c 6.7±0.2%), were studied on 3 occasions (two with vildagliptin and one placebo) in a double-blind, randomised, crossover fashion. On each day, vildagliptin (50mg) or placebo was given orally, followed by intravenous exendin(9-39) (600pmol/kg/min, on 1 of the 2 vildagliptin treatment days) or 0.9% saline over 180min. Between 0-120min, a fat emulsion was infused intraduodenally at 2kcal/min. Energy expenditure, plasma glucose and glucose-regulatory hormones were evaluated. RESULTS:Intraduodenal fat increased plasma GLP-1 and GIP, insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P<0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP-1 was higher (all P<0.05), and energy expenditure tended to be less after vildagliptin (P=0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP-1 (both total and intact), and energy expenditure were higher during intravenous exendin(9-39) than saline (all P<0.05). CONCLUSIONS:In well controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP-1. This article is protected by copyright. All rights reserved.