Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes

https://doi.org/10.1016/j.diabres.2006.12.009Get rights and content

Abstract

This 24-week, double-blind, randomized, multicenter, placebo-controlled, parallel-group study performed in 354 drug-naïve patients with type 2 diabetes (T2DM) assessed efficacy and tolerability of vildagliptin (50 mg qd, 50 mg bid, or 100 mg qd). The primary assessment was change from baseline to endpoint in hemoglobin A1c (A1C), comparing vildagliptin to placebo by ANCOVA. Baseline A1C averaged 8.4% and the between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMΔ) in A1C was −0.5 ± 0.2% (P = 0.011), −0.7 ± 0.2% (P < 0.001), and −0.9 ± 0.2% (P < 0.001) in patients receiving vildagliptin 50 mg qd, 50 mg bid, or 100 mg qd, respectively. Baseline FPG averaged 10.5 mmol/L; the between-treatment difference in AMΔ FPG was −0.6 ± 0.4 mmol/L in patients receiving vildagliptin 50 mg qd and −1.3 ± 0.4 mmol/L (P = 0.001) in both groups receiving 100 mg daily. Relative to baseline, body weight did not change significantly in any of the three vildagliptin groups and decreased by 1.4 ± 0.4 kg in the placebo group. Adverse events (AEs) occurred with similar frequency in each group: 55.8%, 59.3%, 59.3%, and 57.6% of patients receiving vildagliptin 50 mg qd, 50 mg bid, 100 mg qd, or placebo, respectively, experienced an AE. No confirmed hypoglycemia was reported.

Conclusion: Vildagliptin is effective and well-tolerated in drug-naïve patients with T2DM and 100 mg vildagliptin provides similar clinical benefit whether given as single or in divided doses.

Introduction

Vildagliptin is a potent and selective DPP-4 inhibitor that improves islet function by increasing pancreatic α- and β-cell responsiveness to glucose [1], [2]. In two 12-week studies [3], [4] and one recent 24-week study [5] vildagliptin was found to decrease A1C without weight gain and with minimal hypoglycemia. The present 24-week, multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to further ascertain the efficacy and tolerability of vildagliptin, and to evaluate the dose–response of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes (T2DM). Vildagliptin dose regimens of 50 mg qd, 50 mg bid, and 100 mg qd were selected and compared to placebo. This would allow determination of whether vildagliptin exhibits dose-related efficacy and whether bid dosing is necessary to obtain maximum efficacy of a 100 mg daily dose.

Section snippets

Study design

This was a 24-week, double-blind, randomized, placebo-controlled, parallel-group study conducted at 98 centers in the US (88), India (4), and Slovakia (6). Each patient attended one screening visit (Week-2), during which inclusion/exclusion criteria were assessed. Eligible patients were randomized at Visit 2 (baseline) week 0 to receive vildagliptin 50 mg qd, 50 mg bid, 100 mg qd, or placebo in a 1:1:1:1 ratio. Efficacy and tolerability were assessed during 5 additional visits at Weeks 4, 8, 12,

Patients studied

A total of 354 patients were randomized and 340 patients comprised the ITT population. Table 1 summarizes the demographic and baseline metabolic characteristics and disposition of patients in the randomized population. The groups were well balanced at baseline, with a mean age, BMI, A1C, and FPG of ∼51 years, 32.2 kg/m2, 8.4%, and 10.6 mmol/L, respectively. Approximately 54% of patients were Caucasian, and there was a substantial representation of Asian, Hispanic, and black races/ethnicities.

Discussion

In agreement with previous clinical trials of up to 52 weeks in duration [3], [4], [7], [8], the present study ascertained that vildagliptin monotherapy (50 or 100 mg daily) produced a clinically meaningful and statistically significant decrease in A1C in drug-naïve patients with T2DM. The efficacy of 100 mg vildagliptin given once daily was at least as good as when given in divided doses, and vildagliptin was well tolerated with no dose-related trends in the AE profile, did not cause weight

Acknowledgments

The authors gratefully acknowledge the investigators and staff at the 98 participating sites, Shad Razac for operational support, James E. Foley, Ph.D., for scientific and editorial advice and the editorial assistance of, and helpful discussion with, Beth Dunning Lower, Ph.D. This study was funded by Novartis Pharmaceuticals Corporation. A list of investigators is provided in Appendix A.

References (12)

  • B. Kreymann et al.

    Glucagon-like peptide-1 7-36: a physiological incretin in man

    Lancet

    (1987)
  • B. Ahrén et al.

    Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes

    J. Clin. Endocrinol. Metab.

    (2004)
  • A. Mari et al.

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

    J. Clin. Endocrinol. Metab.

    (2005)
  • S. Ristic et al.

    Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response

    Diabetes Obes. Metab.

    (2005)
  • R.E. Pratley et al.

    Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes

    Horm. Metab. Res.

    (2006)
  • S. Dejager et al.

    Efficacy of vildagliptin in drug-naive patients with type 2 diabetes

    Diabetologia

    (2006)
There are more references available in the full text version of this article.

Cited by (303)

View all citing articles on Scopus

This trial (NCT00120536) is registered with ClinicalTrials.gov.

View full text