Exenatide once weekly slows gastric emptying of solids and liquids in healthy, overweight, subjects under steady-state concentrations

Abstract

AIMS: To evaluate the effects of 8 weeks' administration of exenatide once-weekly (ExQW) on gastric emptying of solids and liquids (using the 'gold standard' technique, scintigraphy), glucose absorption and postprandial glycaemia in health. MATERIAL AND METHODS: Thirty two healthy participants were randomized to receive ExQW (2mg per week subcutaneously) (6M,10F; age: 59.9±0.9 yr; BMI: 29.6±0.6 kg/m2 ) or matching placebo (PLAC) (6M,10F; age: 60.6±1.2 yr; BMI: 29.5±1.0 kg/m2 ) for 8 weeks. Gastric emptying, nausea (visual analog scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120min after a solid/liquid meal, comprising 100g ground beef (radiolabelled with 20MBq 99m Tc-sulphur colloid) and 150ml 10% glucose (radiolabelled with 7MBq 67 Ga-EDTA), and containing 5g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. RESULTS: The studies were well tolerated. Scores for nausea were consistently low without any difference between ExQW and PLAC groups. ExQW slowed gastric emptying of solids (e.g. AUC 0-120min: P<0.05) and liquids (e.g. AUC 0-120min: P=0.01) substantially and attenuated glucose absorption (e.g. 3-OMG iAUC 0-30min: P=0.001) and the postprandial rise in plasma glucose (e.g. iAUC 0-30min: P=0.008). Plasma glucagon at 2h was reduced by ExQW (P=0.001). The magnitude of the reduction in plasma glucose at t=30min from baseline to 8 weeks with ExQW was related inversely to the 50% emptying time of the glucose drink (r=-0.55, P=0.03). CONCLUSIONS: In healthy subjects, 8 weeks administration of the 'long-acting' GLP-1RA, ExQW, slows gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia. Clinical Trials Registration Number: ACTRN 12616000955415 This article is protected by copyright. All rights reserved.