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 receivingmonotherapy 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.
RCT Entities:
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.
Authors: David A D'Alessio; Amanda M Denney; Linda M Hermiller; Ronald L Prigeon; Julie M Martin; William G Tharp; Monica Liqueros Saylan; Yanling He; Beth E Dunning; James E Foley; Richard E Pratley Journal: J Clin Endocrinol Metab Date: 2008-10-28 Impact factor: 5.958
Authors: Bo Ahrén; James E Foley; Ele Ferrannini; David R Matthews; Bernard Zinman; Sylvie Dejager; Vivian A Fonseca Journal: Diabetes Care Date: 2010-01-12 Impact factor: 17.152