Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Lee, M. M.Y. et al. (2021) Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation, 143(6), pp. 516-525. (doi: 10.1161/CIRCULATIONAHA.120.052186) (PMID:33186500) (PMCID:PMC7864599)

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Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Lee, Matthew and Docherty, Dr Kieran and Mark, Professor Patrick and Welsh, Professor Paul and Petrie, Professor Mark and Mangion, Dr Kenneth and Woodward, Miss Rosemary and Campbell, Dr Ross and McMurray, Professor John and Berry, Professor Colin and Coyle, Mrs Liz and Brooksbank, Dr Katriona and Jhund, Professor Pardeep and Petrie, Professor John and Wetherall, Miss Kirsty and Lang, Professor Ninian and Roditi, Dr Giles and Sattar, Professor Naveed and Petrie, Dr Colin and Radjenovic, Dr Aleksandra
Authors: Lee, M. M.Y., Brooksbank, K. J.M., Wetherall, K., Mangion, K., Roditi, G., Campbell, R. T., Berry, C., Chong, V., Coyle, L., Docherty, K. F., Dreisbach, J. G., Labinjoh, C., Lang, N. N., Lennie, V., McConnachie, A., Murphy, C. L., Petrie, C. J., Petrie, J. R., Speirits, I. A., Sourbron, S. P., Welsh, P., Woodward, R., Radjenovic, A., Mark, P. B., McMurray, J. J.V., Jhund, P. S., Petrie, M. C., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:13 November 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Circulation 143(6):516-525
Publisher Policy:Reproduced under a Creative Commons License

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