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

Research output: Contribution to journalJournal article

  • Bogdan Balas
  • Muhammad R Baig
  • Catherine Watson
  • Beth E Dunning
  • Monica Ligueros-Saylan
  • Yibin Wang
  • Yan-Ling He
  • Celia Darland
  • Holst, Jens Juul
  • Deacon, Carolyn F.
  • Kenneth Cusi
  • Andrea Mari
  • James E Foley
  • Ralph A DeFronzo
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-(3)H-glucose iv and 1-(14)C-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
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number4
Pages (from-to)1249-55
Number of pages6
ISSN0021-972X
DOIs
Publication statusPublished - 2007

Bibliographical note

Keywords: Adamantane; Adenosine Deaminase; Antigens, CD26; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Glucose; Glycoproteins; Hemoglobin A, Glycosylated; Humans; Hypoglycemic Agents; Islets of Langerhans; Kinetics; Male; Middle Aged; Nitriles; Obesity; Pyrrolidines

ID: 8416966