Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials

Täger, T., Atar, D., Agewall, S., Katus, H. A., Grundtvig, M., Cleland, J. G.F. , Clark, A. L., Fröhlich, H. and Frankenstein, L. (2020) Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Heart Failure Reviews, (doi: 10.1007/s10741-020-09954-8) (PMID:32314085) (Early Online Publication)

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Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of < 52 weeks confirmed the main results. Similar results were obtained when restricting mortality analyses to patients included in cardiovascular outcome trials (n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Täger, T., Atar, D., Agewall, S., Katus, H. A., Grundtvig, M., Cleland, J. G.F., Clark, A. L., Fröhlich, H., and Frankenstein, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Heart Failure Reviews
Publisher:Springer
ISSN:1382-4147
ISSN (Online):1573-7322
Published Online:20 April 2020
Copyright Holders:Copyright © The Author(s) 2020
First Published:First published in Heart Failure Reviews 2020
Publisher Policy:Reproduced under a Creative Commons license

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