SGLT2 Inhibitors in the Prevention and Treatment of Cardiovascular Disease A Review
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Keywords
SGLT2 inhibitors, cardiovascular disease, chronic kidney disease, type 2 diabetes
Abstract
Over the last decade, sodium-glucose transport (SGLT2) inhibitors have become one of the most exhaustively studied classes of medications for cardiometabolic diseases. Although multiple trials have established their benefit, one of the crucial tasks of the medical community is to accelerate their effective adoption into clinical practice by identifying the most appropriate patient population who could benefit from it. To date, this class of medications is indicated in patients with symptomatic (NYHA class II-IV) congestive heart failure with preserved or reduced ejection fraction, chronic kidney disease, or type 2 diabetes with cardiovascular (CV) risk factors. This article focuses on best implementing these medications into clinical practice and reviews their proposed mechanisms of action.
Résumé
Au cours de la dernière décennie, les inhibiteurs du transport du sodium et du glucose (SGLT2) sont devenus l’une des classes de médicaments les plus étudiées dans le traitement des maladies cardiométaboliques. Bien que de multiples essais aient établi leur bénéfice, l’une des tâches cruciales de la communauté médicale est d’accélérer leur adoption effective dans la pratique clinique en identifiant la population de patients la plus appropriée qui pourrait en bénéficier. À ce jour, cette classe de médicaments est indiquée chez les patients souffrant d’insuffisance cardiaque congestive symptomatique (classe II-IV de la NYHA) avec fraction d’éjec-tion préservée ou réduite, de maladie rénale chronique ou de DT2 avec facteurs de risque cardiovasculaire (CV). Cet article se concentre sur la meilleure façon de mettre en œuvre ces médicaments dans la pratique clinique et fournit un examen de leurs mécanismes d’action proposés.
References
2. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117–28.
3. McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZ, Dagogo-Jack S, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021;6(2):148–58.
4. Verma S, McGuire DK, Kosiborod MN. Two Tales: One Story: EMPEROR-Reduced and DAPA-HF. Circulation. 2020 Dec 8;142(23):2201–4.
5. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021 Oct 14;385(16):1451–61.
6. Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022 Sep 22;387(12):1089–98.
7. Fraser S, Swiggum E. sglt2 inhibitor use in patients with type 2 diabetes mellitus and heart failure. Can J Gen Intern Med. 2022;17(SP2):9–16.
8. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021 Jan 14;384(2):117–28.
9. Rao VN, Murray E, Butler J, Cooper LB, Cox ZL, Fiuzat M, et al. In-hospital initiation of sodium-glucose cotransporter-2 inhibitors for heart failure with reduced ejection fraction. J Am Coll Cardiol. 2021 Nov 16;78(20):2004–12.
10. Schulze PC, Bogoviku J, Westphal J, Aftanski P, Haertel F, Grund S, et al. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF). Circulation. 2022 Jul 26;146(4):289–98.
11. Salah HM, Al’Aref SJ, Khan MS, Al-Hawwas M, Vallurupalli S, Mehta JL, 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 Feb 5;21(1):20.
12. Ahmad T, Desai NR, Velazquez EJ. SGLT2 inhibitors should be considered for all patients with heart failure. J Am Coll Cardiol. 2022 Oct 4;80(14):1311–3.
13. Packer M. Six lessons learned from the use of SGLT2 inhibitors in patients with heart failure. Nat Rev Cardiol. 2022 Aug;19(8):499–500.
14. Cook O, Prebtani A. A practical, simple approach to prescribing SGLT-2 inhibitors for glycemic control, heart failure, or chronic renal disease in patients with and without type 2 diabetes mellitus. Can J Gen Intern Med. 2022;17(SP2):17–21.
15. Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015 Sep;38(9):1638–42.
16. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015 Mar;12(2):78–89.
17. Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of Sodium Glucose Co-Transporter 2 (SGLT2) inhibitors: A state-of-the-art review. JACC Basic Transl Sci. 2020 Jun;5(6):632–44.
18. Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020 Dec;17(12):761–72.
19. Hallow KM, Helmlinger G, Greasley PJ, McMurray JJV, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018 Mar;20(3):479–87.
20. Mazidi M, Rezaie P, Gao HK, Kengne AP. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: A systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. J Am Heart Assoc. 2017 May 25;6(6):e004007.
21. Matthews VB, Elliot RH, Rudnicka C, Hricova J, Herat L, Schlaich MP. Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2. J Hypertens. 2017 Oct;35(10):2059–68.
22. Mazer CD, Hare GMT, Connelly PW, Gilbert RE, Shehata N, Quan A, et al. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. Circulation. 2020 Feb 25;141(8):704–7.
23. Juni RP, Kuster DWD, Goebel M, Helmes M, Musters RJP, van der Velden J, et al. Cardiac microvascular endothelial enhancement of cardiomyocyte function is impaired by inflammation and restored by empagliflozin. JACC Basic Transl Sci. 2019 Sep;4(5):575–91.
24. Schork A, Saynisch J, Vosseler A, Jaghutriz BA, Heyne N, Peter A, et al. Effect of SGLT2 inhibitors on body composition, fluid status and renin-angiotensin-aldosterone system in type 2 diabetes: a prospective study using bioimpedance spectroscopy. Cardiovasc Diabetol. 2019 Apr 5;18(1):46.
25. Sato T, Aizawa Y, Yuasa S, Kishi S, Fuse K, Fujita S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018 Jan 4;17(1):6.
26. Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007 Mar 15;356(11):1140–51.
27. Ho KL, Zhang L, Wagg C, Al Batran R, Gopal K, Levasseur J, et al. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc Res. 2019 Sep 1;115(11):1606–16.
28. Li C, Zhang J, Xue M, Li X, Han F, Liu X, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019 Feb 2;18(1):15.
29. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab. 2018 Dec;44(6):457–64.
30. Hare JM, Johnson RJ. Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation. 2003 Apr 22;107(15):1951–3.
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Michael Rheaume , McMaster University, Hamilton, ON, Canada
Department of Medicine, McMaster University, Hamilton, ON, Canada
Aditya Khetan, McMaster University in Hamilton, Ontario
Department of Medicine, McMaster University, Hamilton, ON, Canada
Marie Pigeyre , McMaster University and Population Health Research Institute, Hamilton, Ontario
Department of Medicine, McMaster University, Hamilton, ON, Canada; 2Population Health Research Institute, Hamilton, ON, Canada