Brief Articles
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World J Diabetes. Mar 15, 2010; 1(1): 19-26
Published online Mar 15, 2010. doi: 10.4239/wjd.v1.i1.19
Effect of vildagliptin as add-on therapy to a low-dose metformin
Claudia Filozof, Sherwyn Schwartz, James E Foley
Claudia Filozof, Diabetes Principal Medical Scientific Expert, Novartis Pharma AG, Fabrikstrasse 4-4.43.4, CH-4056 Basel, Switzerland
Sherwyn Schwartz, Diabetes and Glandular Disease Clinic, San Antonio, TX 78229, United States
James E Foley, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, United States
Author contributions: Filozof C and Foley JE wrote this paper on behalf of many individuals at Novartis who contributed to the design, implementation, analysis and reporting of the data including Valentin M, Colin L, Holmes D, Thuren T, Buccheit F, Degen J and Kothny W; Schwartz S wrote this paper as the principal investigator on behalf of the study investigators; Filozof C and Foley J are employees of Novartis Pharmaceuticals Corporation and hold stocks in the company; Schwartz S was involved in the conduct of the study as a clinical trial investigator. No additional known conflict of interest exists and no honoraria were offered or received for coauthor participation in the writing of this manuscript.
Supported by Novartis Pharmaceuticals Corporation, NCT00396357
Correspondence to: Claudia Filozof, MD, PhD, Diabetes Principal Medical Scientific Expert, Novartis Pharma AG, Fabrikstrasse 4-4.43.4, CH-4056 Basel, Switzerland.
Telephone: +41-61-3242987 Fax: +41-61-3247921
Received: October 9, 2009
Revised: January 7, 2010
Accepted: January 14, 2010
Published online: March 15, 2010

AIM: To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus (T2DM) patients who have inadequate control with metformin monotherapy.

METHODS: Eligible patients were randomized to receive vildagliptin 100 mg qd or metformin (500 mg qd for 2 wk and then 500 mg bid) added to open label metformin 500 mg bid for the 24 wk. The primary endpoint was baseline to endpoint hemoglobin A1c (HbA1c) change.

RESULTS: The adjusted mean change from baseline in HbA1c at the 24th wk was -0.51% in the vildagliptin/metformin group (mean baseline HbA1c: 7.4%) and -0.37% in the metformin monotherapy group (mean baseline HbA1c: 7.3%). The mean difference was -0.14% with 95% Confidence Interval (-0.24%, -0.05%). As non-inferiority (margin of 0.4%) was achieved, a test for superiority was performed. This test showed statistically significant superiority of the combination over monotherapy group (P = 0.002). Gastrointestinal (GI) adverse events were significantly more frequent in the metformin group than the combination group (21.0% vs 15.4%, P = 0.032).

CONCLUSION: In patients with T2DM inadequately controlled with metformin up to 1000 mg daily, the addition of vildagliptin 100 mg daily achieved larger HbA1c reduction with fewer GI events than with increasing the metformin dose.

Keywords: Vildagliptin, Metformin, Dipeptidyl peptidase-4, Hemoglobin A1c, Glucagon-like peptide-1, Gastrointestinal side effects