The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study.
BACKGROUND
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.


OBJECTIVE
To determine the effect of sitagliptin on GE in healthy subjects, and the relationships between GE with glycaemia and incretin hormone secretion.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
J E
JE
Stevens
M
M
Horowitz
C F
CF
Deacon
M
M
Nauck
C K
CK
Rayner
K L
KL
Jones
D001786:Blood Glucose / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007408:Intestinal Absorption; D008297:Male; D019518:Postprandial Period; D011719:Pyrazines / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*; D055815:Young Adult
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000068900:Sitagliptin Phosphate