Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes☆
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)
- et al.
Glucagon-like peptide-1 7-36: a physiological incretin in man
Lancet
(1987) - 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) - 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) - et al.
Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response
Diabetes Obes. Metab.
(2005) - et al.
Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes
Horm. Metab. Res.
(2006) - et al.
Efficacy of vildagliptin in drug-naive patients with type 2 diabetes
Diabetologia
(2006)
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This trial (NCT00120536) is registered with ClinicalTrials.gov.