The Metabolic Model of Heart Failure; the Role of Sodium-Glucose Co-transporter 2(SGLT2) Inhibition
Main Article Content
Abstract
The sodium-glucose co-transporter-2-inhibitors (SGLT2I) recently gained a unique role in managing the heart failure reduced ejection fraction. These inhibitors reduce cardiovascular (CV) risk factors, including plasma glucose, blood pressure, albuminuria, body weight, and renal events in the long term. The clinical trials proved their role in reducing hospitalization for HF, CV and all-cause mortality, atherosclerosis-related events, and CKD progression. Initiating this medication on decompensated heart failure or post-discharge reduces the risk of re-hospitalization. These co-transporter inhibitors reduced heart failure and kidney events regardless of baseline biomarker concentration or diabetes mellitus status. This article aims to the metabolic paradigm and cellular metabolism by exposing the available clinical trials of this novel therapy for heart failure, uncovering the possible mechanisms of action on the CV system, and describing the positive effect on prognostic markers as pro-BNP, as well as changing the plasma renin-aldosterone activity, cardiac troponin T (hs-cTnT), and insulin-like growth factor-binding protein 7 (IGFBP7).
Article Details
How to Cite
SHABAN, Mohammed et al.
The Metabolic Model of Heart Failure; the Role of Sodium-Glucose Co-transporter 2(SGLT2) Inhibition.
Medical Research Archives, [S.l.], v. 10, n. 6, june 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2828>. Date accessed: 26 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i6.2828.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Wagdy K, Nagy S. EMPEROR-Preserved: SGLT2 inhibitors breakthrough in the management of heart failure with preserved ejection fraction. Glob Cardiol Sci Pract. 2021;2021(3). doi:10.21542/GCSP.2021.17
3. Salah HM, Al'Aref SJ, Khan MS, et al. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol 2022 211. 2022;21(1):1-8. doi:10.1186/S12933-022-01455-2
4. Herat LY, Matthews J, Azzam O, Schlaich MP, Matthews VB. Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition. Curr Hypertens Rep. Published online March 2, 2022. doi:10.1007/S11906-022-01170-Z
5. Herrington WG, Savarese G, Haynes R, et al. Cardiac, renal, and metabolic effects of sodium-glucose cotransporter 2 inhibitors: a position paper from the European Society of Cardiology ad-hoc task force on sodium-glucose cotransporter 2 inhibitors. Eur J Heart Fail. 2021;23(8):1260-1275. doi:10.1002/EJHF.2286
6. Fu JL, Yu Q, Li M Di, Hu CM, Shi G. Deleterious cardiovascular effect of exosome in digitalis-treated decompensated congestive heart failure. J Biochem Mol Toxicol. 2020;34(5). doi:10.1002/JBT.22462
7. Savino JA, Kosmas CE, Wagman G, Vittorio TJ. Evolution of the Chronic Congestive Heart Failure Paradigm. Cardiol Rev. 2013;21(3):121-126. doi:10.1097/CRD.0b013e318277c990
8. Ghionzoli N, Gentile F, Del Franco AM, et al. Current and emerging drug targets in heart failure treatment. Heart Fail Rev. Published online 2021. doi:10.1007/S10741-021-10137-2
9. Burnett JC. Vericiguat — Another Victory for Targeting Cyclic GMP in Heart Failure. N Engl J Med. 2020;382(20):1952-1953. doi:10.1056/NEJME2006855/SUPPL_FILE/NEJME2006855_DISCLOSURES.PDF
10. Breitenstein S, Roessig L, Sandner P, Lewis KS. Novel sGC Stimulators and sGC Activators for the Treatment of Heart Failure. Handb Exp Pharmacol. 2017;243:225-247. doi:10.1007/164_2016_100
11. Reginauld SH, Cannone V, Iyer S, et al. Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP. JACC Heart Fail. 2019;7(10):891-898. doi:10.1016/J.JCHF.2019.05.012
12. Markham A, Duggan S. Vericiguat: First Approval. Drugs. 2021;81(6):721-726. doi:10.1007/S40265-021-01496-Z
13. PW A, B P, KJ A, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020;382(20). doi:10.1056/NEJMOA1915928
14. Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMOA2022190
15. Fang JC. Heart-Failure Therapy — New Drugs but Old Habits? N Engl J Med. 2019;381(21):2063-2064. doi:10.1056/NEJME1912180/SUPPL_FILE/NEJME1912180_DISCLOSURES.PDF
16. Packer M, Anker SD, Butler J, et al. Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial. Eur Heart J. 2021;42(6). doi:10.1093/EURHEARTJ/EHAA968
17. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMOA1911303
18. McMurray JJV, DeMets DL, Inzucchi SE, et al. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019;21(11):1402-1411. doi:10.1002/EJHF.1548
19. Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation. 2020;141(2):100-111. doi:10.1161/CIRCULATIONAHA.119.044133
20. Jhund PS, Solomon SD, Docherty KF, et al. Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. Circulation. 2021;143(4):298-309. doi:10.1161/CIRCULATIONAHA.120.050391
21. Shen L, Kristensen SL, Bengtsson O, et al. Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists: An Analysis of DAPA-HF. JACC Heart Fail. 2021;9(4):254-264. doi:10.1016/J.JCHF.2020.11.009
22. McMurray JJV, Packer M, Desai AS, et al. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail. 2014;16(7):817-825. doi:10.1002/EJHF.115
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