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Effects of Dipeptidyl Peptidase 4 Inhibition on Gastrointestinal Function, Meal Appearance and Glucose Metabolism in Type 2 Diabetes

¹Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN
²Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN
³Novartis Pharmaceuticals, East Hanover, NJ
⁴PharmaWrite, LLC, Princeton, NJ

Correspondence: vella.adrian{at}mayo.edu

Key Words: DPP-IV inhibition • meal appearance • gastric emptying • incretins

OBJECTIVE: To determine if alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations.

METHODS: We simultaneously measured gastric emptying, meal appearance, endogenous glucose production and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg bid) or placebo for 10 days using a double blind, placebo-controlled randomized crossover design.

RESULTS: Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (p < 0.01) after vildagliptin than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5h, p< 0.05) and GLP-1 concentrations were higher (1878 ± 270 vs. 1277 ± 312 pmol/l per 5h, p = 0.001) during vildagliptin administration compared to placebo. Gastric emptying, and meal appearance did not differ between treatments.

CONCLUSIONS: Vildagliptin does not alter gastric emptying, or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to the systemic circulation. Alterations in islet function secondary to increased circulating concentrations of active GLP-1 are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.

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