The effect of dipeptidyl peptidase-4 inhibition on gastric volume, satiation and enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled crossover study.
OBJECTIVE
The incretin hormone glucagon-like peptide-1 (GLP-1) retards gastric emptying and decreases caloric intake. It is unclear whether increased GLP-1 concentrations achieved by inhibition of the inactivating enzyme dipeptidyl peptidase-4 (DPP-4) alter gastric volumes and satiation in people with type 2 diabetes.


METHODS
In a double-blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50 mg bid) or placebo for 10 days in random order separated by a 2-week washout. On day 7, fasting and postmeal gastric volumes were measured by a (99m)Tc single-photon emission computed tomography (SPECT) method. On day 8, a liquid Ensure meal was consumed at 30 ml/min, and maximum tolerated volume (MTV) and symptoms 30 min later were measured using a visual analogue scale (VAS) to assess effects on satiation. On day 10, subjects ingested water until maximum satiation was achieved. The volume ingested was recorded and symptoms similarly measured using a VAS.


RESULTS
Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 +/- 21 vs. 247 +/- 19 ml, P = 0.98) and fed (746 +/- 28 vs. 772 +/- 26 ml, P = 0.54) gastric volumes did not differ when subjects received vildagliptin or placebo. Treatment with vildagliptin did not alter the MTV of Ensure (1657 +/- 308 vs. 1389 +/- 197 ml, P = 0.15) or water compared to placebo (1371 +/- 141 vs. 1172 +/- 156 ml, P = 0.23). Vildagliptin was associated with decreased peptide YY (PYY) concentrations 60 min after initiation of the meal (166 +/- 27 vs. 229 +/- 34 pmol/l, P = 0.01).


CONCLUSIONS
Vildagliptin does not alter satiation or gastric volume in people with type 2 diabetes despite elevated GLP-1 concentrations. Compensatory changes in enteroendocrine secretion could account for the lack of gastrointestinal symptoms.
Vella
Adrian
A
Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN 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
Deacon
Carolyn F
CF
Foley
James E
JE
Rizza
Robert A
RA
Camilleri
Michael
M
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010919:Placebos; D019518:Postprandial Period / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D012527:Satiation / Q000187:drug effects* / Q000502:physiology; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D054439:Ghrelin; D007004:Hypoglycemic Agents; D009570:Nitriles; D010919:Placebos; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane