Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database

Diabetes Obes Metab. 2008 Sep;10(10):931-8. doi: 10.1111/j.1463-1326.2007.00835.x. Epub 2007 Dec 17.

Abstract

Aim: To assess the effects of 24-week treatment with vildagliptin on measures of beta-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM).

Methods: Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of beta-cell function [homeostasis model assessment of beta-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test-derived) measures of beta-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29).

Results: In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between-treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/- 0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test-derived parameters, and ISR/G (between-treatment difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta = 0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo.

Conclusions: Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test-derived measures of beta-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov.

Trial registration: ClinicalTrials.gov NCT00099866 NCT00099905 NCT00099918 NCT00101673 NCT00101803 NCT00120536.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Aged
  • Biomarkers / blood
  • Blood Glucose / analysis
  • C-Peptide / analysis
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Nitriles / therapeutic use*
  • Pyrrolidines / therapeutic use*
  • Vildagliptin

Substances

  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Nitriles
  • Pyrrolidines
  • Vildagliptin
  • Adamantane

Associated data

  • ClinicalTrials.gov/NCT00099866
  • ClinicalTrials.gov/NCT00099905
  • ClinicalTrials.gov/NCT00099918
  • ClinicalTrials.gov/NCT00101673
  • ClinicalTrials.gov/NCT00101803
  • ClinicalTrials.gov/NCT00120536