Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes

Koichiro Azuma, Zofia Rádiková, Juliet Mancino, Frederico G.S. Toledo, Ernestine Thomas, Cyrous Kangani, Chiara Dalla Man, Claudio Cobelli, Jens J. Holst, Carolyn F. Deacon, Yan Ling He, Monica Ligueros-Saylan, Denise Serra, James E. Foley, David E. Kelley

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100 Citations (Scopus)

Abstract

Objective: Pharmacological inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor vildagliptin prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A1c of 7.1 ± 0.2% completed a crossover study with 6 wk of treatment with vildagliptin and 6 wk with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a two-step glucose clamp performed at 20 and 80 mU/min·m2 insulin infusions. Results: Vildagliptin increased postprandial glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide by 3- and 2-fold, respectively, reduced fasting plasma glucose and postprandial plasma glucose by 1.3 ± 0.3 mmol/liter and 1.6 ± 0.3 mmol/liter (both P <0.01), and improved glucose responsiveness of insulin secretion by 50% (P < 0.01). Vildagliptin lowered postprandial glucagon by 16% (P<0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved after vildagliptin (P < 0.01). Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number2
DOIs
Publication statusPublished - 2008 Feb

ASJC Scopus subject areas

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

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    Azuma, K., Rádiková, Z., Mancino, J., Toledo, F. G. S., Thomas, E., Kangani, C., Dalla Man, C., Cobelli, C., Holst, J. J., Deacon, C. F., He, Y. L., Ligueros-Saylan, M., Serra, D., Foley, J. E., & Kelley, D. E. (2008). Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 93(2), 459-464. https://doi.org/10.1210/jc.2007-1369