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.
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Objectives: The Incretin hormone glucagon-like peptide-1 (GLP-1) retards gastric emptying, and decreases caloric intake. It is unclear if 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 (50mg bid) or placebo for 10-days in random order separated by a 2-week washout. On day 7, fasting and post-meal gastric volumes were measured by a (99m)Tc-SPECT method. On day 8, a liquid Ensure((R)) meal was consumed at 30 ml/min, and maximum tolerated volume (MTV) as well as symptoms 30 minutes later were measured using visual analog scales (VAS) to assess effects on satiation. On day 10, subjects ingested water till maximum satiation was achieved. Volume ingested was recorded and symptoms similarly measured using VAS. Results: Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 + 21 vs. 247 + 19ml, p= 0.98) and fed (746 + 28 vs. 772 + 26ml, p= 0.54) gastric volumes, did not differ when subjects received vildagliptin or placebo. Treatment with vildagliptin did not alter the maximum tolerated volume of Ensure((R)) (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 PYY concentrations 60 minutes 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 status||Published - 2008|