Dataset Information

Efficacy and Safety of Vildagliptin as Add-on to Metformin in Japanese Patients with Type 2 Diabetes Mellitus.

ABSTRACT:

Introduction

The objective of this study was to evaluate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase-4 inhibitor, as an add-on to metformin in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods

This multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-arm study compared vildagliptin 50 mg bid with placebo in T2DM patients who were inadequately controlled [glycosylated hemoglobin (HbA1c) 7.0-10.0%] on a stable daily dose of metformin monotherapy (250 mg bid or 500 mg bid).

Results

A total of 139 patients were randomized to receive either vildagliptin (n = 69) or placebo (n = 70). Patient demographics were comparable between the groups at baseline. After 12 weeks of treatment, adjusted mean change in HbA1c was -1.1% in the vildagliptin group (baseline 8.0%) and -0.1% in the placebo group (baseline 8.0%), with a between-treatment difference of -1.0% (P < 0.001). Vildagliptin showed a similar reduction in HbA1c of -1.1% for both the subpopulations of patients receiving metformin 250 mg bid or 500 mg bid (P < 0.001 vs. baseline). Significantly more patients in the vildagliptin group achieved an HbA1c target of ≤6.5% (30.9%) and <7.0% (64.1%) compared with the placebo group (P < 0.001). The between-treatment difference in adjusted mean change in fasting plasma glucose was -1.6 mmol/L (P < 0.001) in favor of vildagliptin. Patients in the vildagliptin and placebo groups reported comparable incidences of adverse events (44.1% vs. 41.4%). No deaths or hypoglycemic events were reported in the study.

Conclusions

Vildagliptin 50 mg bid added to metformin improved glycemic control without any tolerability issues and hypoglycemia in Japanese patients with T2DM inadequately controlled on metformin monotherapy.

SUBMITTER: Odawara M

PROVIDER: S-EPMC4065285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionTo assess the efficacy and safety of vildagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM), inadequately controlled on stable long-acting, intermediate-acting, or pre-mixed insulin, with or without concomitant metformin.MethodsIn this 12-week placebo-controlled study, patients were randomized to receive either vildagliptin 50 mg twice daily (bid) or placebo treatment in a 1:1 ratio. The primary endpoint was change in glycated hemoglobin A1c (HbA1c) from baseline to 12-week endpoint. Secondary endpoints included proportion of patients achieving pre-defined HbA1c targets of ≤6.5%, <7.0%, and HbA1c <7.0% in patients with baseline HbA1c ≤8.0% and change in fasting plasma glucose (FPG) after 12 weeks of treatment. Regular monitoring was performed to record any treatment-emergent adverse events (AEs) and serious adverse events or hypoglycemic episodes.ResultsOf the 156 patients randomized, 96.8% completed the study (vildagliptin, n = 76; placebo, n = 75). Patient demographics and clinical characteristics were comparable between the groups at baseline. Addition of vildagliptin resulted in statistically significant reductions in HbA1c after 12 weeks (-1.01 ± 0.06%), with a between-treatment difference of -0.91 ± 0.09% (p < 0.001). FPG levels reduced from baseline to 12 weeks in the vildagliptin group (-1.2 ± 0.2 mmol/L), with a between-treatment difference of -1.2 ± 0.3 mmol/L which was significant (p < 0.001). The proportion of patients achieving HbA1c targets was higher with vildagliptin treatment for all pre-defined responder rate categories. The overall incidence of AEs was comparable between groups (vildagliptin, 46.2% vs. placebo, 43.6%). The overall incidence of hypoglycemic events was low and all events were self-treatable without using drug therapy. No severe hypoglycemic events were reported.ConclusionTreatment with vildagliptin 50 mg bid as add-on to insulin with or without metformin resulted in statistically significant reductions in HbA1c in Japanese patients with T2DM. Overall, vildagliptin was well tolerated with a safety profile similar to that of placebo in this patient population. ClinicalTrials.gov Identifier, NCT02002221 FUNDING: Novartis Pharma K.K.

Project description:INTRODUCTION:The use of dipeptidyl peptidase-4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus (T2DM), but no single-pill combination (SPC) is currently available in Japan. The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy. METHODS:This was a 14-week, randomized, double-blind, parallel-group, placebo-controlled trial. 171 patients with T2DM inadequately controlled [HbA1c (glycosylated hemoglobin) 7.0-10.0%] with vildagliptin 50 mg twice daily (bid) were randomized (2:1) to receive either a vildagliptin/metformin SPC (n = 115) or matching vildagliptin/placebo SPC (n = 56). RESULTS:Baseline demographics and background characteristics were generally comparable between the treatment groups. The change in HbA1c [mean ± standard error (SE)] was -0.8 ± 0.1% in the vildagliptin/metformin SPC (baseline HbA1c, 7.9 ± 0.1%) group and 0.1 ± 0.1% in the vildagliptin/placebo SPC (baseline HbA1c, 8.0 ± 0.1%) group, with a between-treatment difference of -1.0 ± 0.1% (P <0.001) in favor of the vildagliptin/metformin SPC group. The proportion of patients achieving target HbA1c <7.0% was significantly higher with vildagliptin/metformin SPC compared with vildagliptin/placebo SPC (45.8% vs. 13.5%, P <0.001). The overall incidences of adverse events (AEs) were 43.5% in the vildagliptin/metformin SPC and 67.9% in the vildagliptin/placebo SPC group. The incidences of serious AEs were low in both the treatment groups (0.9% vs. 3.6%, respectively). Body weight remained constant throughout the study in both the treatment groups. There were no deaths or hypoglycemic events during the study. CONCLUSIONS:Switching Japanese patients with T2DM requiring treatment intensification, from vildagliptin monotherapy to a vildagliptin/metformin SPC (50/250 or 50/500 mg) was efficacious and safe, eliciting significant reduction in HbA1c without increased risk of hypoglycemia and weight gain.

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