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.

Aim: 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.