Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure

Overview

Journal J Cardiovasc Dev Dis

Specialty Cardiology & Vascular Diseases

Date 2022 Jul 25

PMID 35877587

Authors

Dominik Kurczynski

Bartosz Hudzik

Marta Jagosz

Jan Zabierowski

Jolanta Nowak

Andrzej Tomasik

Arkadiusz Badzinski

Piotr Rozentryt

Mariusz Gasior

Affiliations

Soon will be listed here.

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently the second-line pharmacotherapy in type 2 diabetes, particularly through their effectiveness in reducing glycemia, but also due to their cardioprotective and nephroprotective effects. In light of surprisingly satisfactory results from large, randomized trials on gliflozins, SGLT2 received the highest recommendation (Class IA) with the highest level of evidence (A) in the treatment algorithm for HF with reduced LVEF in recent ESC HF guidelines. This great breakthrough in the treatment of HF is due to different mechanisms of action of gliflozins that are reported to be able to change the natural course of HF by reducing the risk of both hospitalization and death. They are recommended regardless of the patient's diabetes status. This review summarizes the up-to-date literature on their beneficial and pleiotropic impact on the cardiovascular system.

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References

Wiviott S, Raz I, Bonaca M, Mosenzon O, Kato E, Cahn A . Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2018; 380(4):347-357. DOI: 10.1056/NEJMoa1812389. View

Cosentino F, Grant P, Aboyans V, Bailey C, Ceriello A, Delgado V . 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019; 41(2):255-323. DOI: 10.1093/eurheartj/ehz486. View

Lambers Heerspink H, de Zeeuw D, Wie L, Leslie B, List J . Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013; 15(9):853-62. PMC: 3906841. DOI: 10.1111/dom.12127. View

Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle H . Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2014; 1(3):208-19. DOI: 10.1016/S2213-8587(13)70084-6. View

Horton J, Davidson M, Kurishima C, Vega R, Powers J, Matsuura T . The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight. 2019; 4(4). PMC: 6478419. DOI: 10.1172/jci.insight.124079. View

Bedi Jr K, Snyder N, Brandimarto J, Aziz M, Mesaros C, Worth A . Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure. Circulation. 2016; 133(8):706-16. PMC: 4779339. DOI: 10.1161/CIRCULATIONAHA.115.017545. View

Zelniker T, Braunwald E . Cardiac and Renal Effects of Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetes: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018; 72(15):1845-1855. DOI: 10.1016/j.jacc.2018.06.040. View

Inoue B, Dos Santos L, Pessoa T, Antonio E, Pacheco B, Savignano F . Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure. Am J Physiol Regul Integr Comp Physiol. 2011; 302(1):R166-74. DOI: 10.1152/ajpregu.00127.2011. View

Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R . Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016; 65(5):1190-5. DOI: 10.2337/db15-1356. View

10.

Sato T, Aizawa Y, Yuasa S, Kishi S, Fuse K, Fujita S . The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018; 17(1):6. PMC: 5753537. DOI: 10.1186/s12933-017-0658-8. View

11.

Chilton R, Tikkanen I, Cannon C, Crowe S, Woerle H, Broedl U . Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015; 17(12):1180-93. PMC: 5057299. DOI: 10.1111/dom.12572. View

12.

Skrtic M, Cherney D . Sodium-glucose cotransporter-2 inhibition and the potential for renal protection in diabetic nephropathy. Curr Opin Nephrol Hypertens. 2014; 24(1):96-103. DOI: 10.1097/MNH.0000000000000084. View

13.

Wanner C, Inzucchi S, Zinman B . Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016; 375(18):1801-2. DOI: 10.1056/NEJMc1611290. View

14.

Heerspink H, Stefansson B, Correa-Rotter R, Chertow G, Greene T, Hou F . Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020; 383(15):1436-1446. DOI: 10.1056/NEJMoa2024816. View

15.

Davies M, DAlessio D, Fradkin J, Kernan W, Mathieu C, Mingrone G . Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41(12):2669-2701. PMC: 6245208. DOI: 10.2337/dci18-0033. View

16.

Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thevenet J . Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015; 21(5):512-7. DOI: 10.1038/nm.3828. View

17.

Tanaka H, Takano K, Iijima H, Kubo H, Maruyama N, Hashimoto T . Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus. Adv Ther. 2016; 34(2):436-451. PMC: 5331075. DOI: 10.1007/s12325-016-0457-8. View

18.

Feng M, Lv H, Xu X, Wang J, Lyu W, Fu S . Efficacy and safety of dapagliflozin as monotherapy in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019; 98(30):e16575. PMC: 6709066. DOI: 10.1097/MD.0000000000016575. View

19.

Packer M . Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors: identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress. Cardiovasc Res. 2020; 117(1):74-84. DOI: 10.1093/cvr/cvaa064. View

20.

Lytvyn Y, Bjornstad P, Udell J, Lovshin J, Cherney D . Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials. Circulation. 2017; 136(17):1643-1658. PMC: 5846470. DOI: 10.1161/CIRCULATIONAHA.117.030012. View