Premium
Robust improvements in fasting and prandial measures of β‐cell function with vildagliptin in drug‐naïve patients: analysis of pooled vildagliptin monotherapy database
Author(s) -
Pratley R. E.,
Schweizer A.,
Rosenstock J.,
Foley J. E.,
Banerji M. A.,
PiSunyer F. X.,
Mills D.,
Dejager S.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00835.x
Subject(s) - vildagliptin , placebo , medicine , proinsulin , insulin , endocrinology , population , type 2 diabetes , meal , diabetes mellitus , gastroenterology , alternative medicine , environmental health , pathology
Aim: To assess the effects of 24‐week treatment with vildagliptin on measures of β‐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 β‐cell function [homeostasis model assessment of β‐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 β‐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 (AMΔ) = 10.3 ± 1.5] and vs. placebo (between‐treatment difference in AMΔ = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMΔ = −0.05 ± 0.01) and vs. placebo (between‐treatment difference in AMΔ = −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 AMΔ = 9.8 ± 2.8 pmol/min/m 2 /mM, p < 0.001) and the insulinogenic index 0–peak glucose (between‐treatment difference in AMΔ = 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 β‐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.