The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

Bogdan Balas, Muhammad R. Baig, Catherine Watson, Beth E. Dunning, Monica Ligueros-Saylan, Yibin Wang, Yan Ling He, Celia Darland, Jens J. Holst, Carolyn F. Deacon, Kenneth Cusi, Andrea Mari, James E. Foley, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

Aims/Hypothesis: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism( s) by which vildagliptin promotes reduction in plasma glucose concentration. Methods: Sixteen patients with type 2 diabetes (age, 48 ± 3 yr; body mass index, 34.4 ± 1.7 kg/m2; hemoglobin A1c, 9.0 ± 0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3- 3H-glucose iv and 1-14C-glucose orally). Results: After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02 ± 0.06 vs. 0.74 ± 0.06 mg·kg-1·min-1; P = 0.004), and insulin secretion rate increased by 21% (P = 0.003) despite significant reduction in mean plasma glucose (213 ± 4 vs. 230 ± 4 mg/dl; P = 0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P = 0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P < 0.02). The decline in EGP was positively correlated (r = 0.55; P < 0.03) with the decrease in fasting plasma glucose (change = -14 mg/dl). Conclusions: During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.

Original languageEnglish (US)
Pages (from-to)1249-1255
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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