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Type: Journal article
Title: The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study
Author: Stevens, J.
Horowitz, M.
Deacon, C.
Nauck, M.
Rayner, C.
Jones, K.
Citation: Alimentary Pharmacology and Therapeutics, 2012; 36(4):379-390
Publisher: Blackwell Publishing Ltd
Issue Date: 2012
ISSN: 0269-2813
Statement of
J. E. Stevens, M. Horowitz, C. F. Deacon, M. Nauck, C. K. Rayner & K. L. Jones
Abstract: <h4>Background</h4>The rate of gastric emptying (GE) and subsequent release of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are critical determinants of postprandial glycaemia in health and type 2 diabetes. Slowing of GE may be the dominant mechanism by which exogenous GLP-1, and some GLP-1 analogues, improve postprandial glycaemia.<h4>Aim</h4>To determine the effect of sitagliptin on GE in healthy subjects, and the relationships between GE with glycaemia and incretin hormone secretion.<h4>Methods</h4>Fifteen volunteers (22.8 ± 0.7 years) were studied on two occasions following 2 days dosing with sitagliptin (100 mg/day) or placebo. GE (scintigraphy), glycaemia and plasma GLP-1 and GIP (total and intact), insulin and glucagon were measured for 240 min following a mashed potato meal (1808 kJ).<h4>Results</h4>There was no difference in GE between sitgaliptin and placebo [50% emptying time (T50): P = 0.4]. Mean blood glucose was slightly less (P = 0.02) on sitagliptin. Sitagliptin reduced plasma glucagon between 75 and 120 min (P < 0.05), and increased intact GLP-1 (P = 0.0002) and intact GIP (P = 0.0001) by approximately twofold, but reduced total GIP (P = 0.0003) and had no effect on total GLP-1 (P = 0.16) or insulin (P = 0.75). On sitagliptin the initial rise in blood glucose (r = -0.66, P = 0.008) and the intact GIP response (r = -0.66, P = 0.007) were inversely related, whereas the intact GLP-1 response was related directly (r = 0.52, P = 0.05) to the T50.<h4>Conclusions</h4>While the effects of sitagliptin on glycaemic control are unlikely to relate to slowing of GE in healthy humans, the rate of GE is a significant determinant of postprandial glycaemia on sitagliptin.
Keywords: Humans
Gastric Inhibitory Polypeptide
Blood Glucose
Gastric Emptying
Intestinal Absorption
Postprandial Period
Glucagon-Like Peptide 1
Dipeptidyl-Peptidase IV Inhibitors
Young Adult
Sitagliptin Phosphate
Rights: © 2012 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2036.2012.05198.x
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