Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial

McMurray, J. J.V. , Ponikowski, P., Bolli, G. B., Lukashevich, V., Kozlovski, P., Kothny, W., Lewsey, J. D. and Krum, H. (2018) Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC: Heart Failure, 6(1), pp. 8-17. (doi:10.1016/j.jchf.2017.08.004) (PMID:29032139)

[img]
Preview
Text
147511.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

903kB

Abstract

Objectives: This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction. Background: Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals. Methods: Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] <0.40) were randomized to 52 weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated with a sulfonylurea) or matching placebo. The primary endpoint was between-treatment change from baseline in echocardiographic LVEF using a noninferiority margin of −3.5%. Results: A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: −2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of −3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: −0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A1c from baseline to 16 weeks, the main secondary endpoint, was greater in the vildagliptin group: −0.62% (95% CI: −0.93 to −0.30%; p < 0.001; −6.8 mmol/mol; 95% CI: −10.2 to −3.3 mmol/mol). Conclusions: Compared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868)

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lewsey, Professor Jim and McMurray, Professor John
Authors: McMurray, J. J.V., Ponikowski, P., Bolli, G. B., Lukashevich, V., Kozlovski, P., Kothny, W., Lewsey, J. D., and Krum, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Health Economics and Health Technology Assessment
Journal Name:JACC: Heart Failure
Publisher:Elsevier Inc.
ISSN:2213-1779
ISSN (Online):2213-1787
Published Online:11 October 2017
Copyright Holders:Copyright © 2017 American College of Cardiology Foundation
First Published:First published in JACC: Heart Failure 6(1): 8-17
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

University Staff: Request a correction | Enlighten Editors: Update this record