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

Clin Endocrinol (Oxf). 2008 Nov;69(5):737-44. doi: 10.1111/j.1365-2265.2008.03235.x. Epub 2008 Mar 10.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Double-Blind Method
  • Drinking / physiology
  • Eating / physiology
  • Enteroendocrine Cells / drug effects*
  • Enteroendocrine Cells / metabolism
  • Fasting / blood
  • Fasting / metabolism
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology
  • Ghrelin / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Middle Aged
  • Nitriles / pharmacology*
  • Organ Size / drug effects
  • Placebos
  • Postprandial Period / drug effects
  • Pyrrolidines / pharmacology*
  • Satiation / drug effects*
  • Satiation / physiology
  • Stomach / drug effects*
  • Stomach / pathology
  • Vildagliptin

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Ghrelin
  • Hypoglycemic Agents
  • Nitriles
  • Placebos
  • Pyrrolidines
  • Glucagon-Like Peptide 1
  • Vildagliptin
  • Adamantane