Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes.
OBJECTIVE
We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations.


METHODS
We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design.


RESULTS
Fasting (7.3 +/- 0.5 vs. 7.9 +/- 0.5 mmol/l) and peak postprandial (14.1 +/- 0.6 vs. 15.9 +/- 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 +/- 1.6 vs. 23.7 +/- 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 +/- 270 vs. 1,277 +/- 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments.


CONCLUSIONS
Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.
Vella
Adrian
A
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. vella.adrian@mayo.edu
Bock
Gerlies
G
Giesler
Paula D
PD
Burton
Duane B
DB
Serra
Denise B
DB
Saylan
Monica Ligueros
ML
Dunning
Beth E
BE
Foley
James E
JE
Rizza
Robert A
RA
Camilleri
Michael
M
D058892:Adenosine Deaminase Inhibitors; D001066:Appetite; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D004435:Eating; D005215:Fasting; D005746:Gastric Emptying; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D019518:Postprandial Period
D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4