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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
Author(s) -
Vella Adrian,
Bock Gerlies,
Giesler Paula D.,
Burton Duane B.,
Serra Denise B.,
Saylan Monica Ligueros,
Deacon Carolyn F.,
Foley James E.,
Rizza Robert A.,
Camilleri Michael
Publication year - 2008
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03235.x
Subject(s) - vildagliptin , crossover study , endocrinology , medicine , peptide yy , gastric emptying , incretin , placebo , glucagon like peptide 1 , type 2 diabetes , gastric inhibitory polypeptide , meal , dipeptidyl peptidase 4 , dipeptidyl peptidase , postprandial , diabetes mellitus , insulin , glucagon , chemistry , stomach , neuropeptide , neuropeptide y receptor , enzyme , biochemistry , alternative medicine , receptor , pathology
Summary Objectives 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.