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

Abstract

SummaryObjectives-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.

Effects of Sitagliptin on Glycemia, Incretin Hormones, and Antropyloroduodenal Motility in Response to Intraduodenal Glucose Infusion in Healthy Lean and Obese Humans and Patients With Type 2 Diabetes Treated With or Without Metformin

“…This might relate to the effects of peptide YY (PYY), whose degradation from PYY1-36 to PYY3-36, which has more potent effects to slow gastric emptying, is prevented by DPP-4 inhibition (50). The current data are thus in keeping with the majority of evidence that DPP-4 inhibition does not influence gastric emptying (17)(18)(19)21,22), although a recent study reported slowing of oral glucose emptying after sitagliptin in type 2 diabetic patients (20). Metformin was reported to slow gastric emptying in mice (25), but we did not observe any effect on APD motility in the current experimental setting.…”

“…The majority of studies have reported a lack of effect of DPP-4 inhibitors on gastric emptying for unclear reasons (16)(17)(18)(19)(20)(21)(22). Although endogenous GLP-1 slows gastric emptying through suppression of antral motility and stimulation of pyloric contractions (6,7), the effect of DPP-4 inhibitors on these motor mechanisms has not been assessed.…”

Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism

“…An important effect of GLP-1 receptor agonists is a direct action on the brain stem to induce satiety and inhibit gastric emptying [59]. A variety of methods have been used to assess appetite and gastric emptying directly, including rate of ingested glucose into the circulation, surrogates of appetite such as ghrelin and gastrin levels or the paracetamol test of gastric emptying and findings indicate that DPP-4 inhibitors have no effect on satiety and gastric emptying [59,60,[91][92][93][94][95]. The prevailing evidence suggests that the effect of GLP-1 on satiety and gastric emptying requires doses of GLP-1 that are much higher than those achieved by DPP-4 inhibition [94].…”

“…Although data is lacking for any direct mechanism that can explain this weight mitigation, one potential mechanism is the mobilisation and burning of fat during meals and another is the reduction in Apo B-48 secretion leading to decreased fat extraction from the gut. In contrast to GLP-1 receptor agonists, there is no satiety effect with DPP-4 inhibitors [91].…”

Effects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels

“…The plasma glucose and serum insulin levels were measured by Hokenkagaku Institute Inc. (Yokohama, Japan). The serum total PYY (PYY 1-36 and PYY ) and plasma obestatin levels were measured using an EIA kit (Yanaihara Institute Inc., Shizuoka, Japan), and the plasma CCK (CCK [26][27][28][29][30][31][32][33] ) levels were also measured using an EIA kit (Phoenix Pharmaceutical, Inc., USA). Active ghrelin was measured using an ELISA (Sceti, Tokyo, Japan).…”