Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes

J Clin Endocrinol Metab. 2005 Aug;90(8):4888-94. doi: 10.1210/jc.2004-2460. Epub 2005 May 10.

Abstract

Aims/hypothesis: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function.

Methods: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors.

Results: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo.

Conclusion: Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / analogs & derivatives*
  • Adenosine Deaminase Inhibitors*
  • Adult
  • Blood Glucose
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl Peptidase 4
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Glycoproteins / antagonists & inhibitors*
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism
  • Male
  • Middle Aged
  • Models, Biological
  • Nitriles
  • Pyrrolidines
  • Treatment Outcome
  • Vildagliptin

Substances

  • Adenosine Deaminase Inhibitors
  • Blood Glucose
  • C-Peptide
  • Enzyme Inhibitors
  • Glycoproteins
  • Insulin
  • Nitriles
  • Pyrrolidines
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Vildagliptin
  • Adamantane