Use of SGLT-2 Inhibitors in Acute Myocardial Infarction
Received: 2026-07-04 20:11:57
Published: 2026-03-29
Abstract
Cardiorenometabolic syndrome (CRMS) is a multifactorial clinical condition reflecting complex and interrelated pathobiological processes involving the cardiovascular, renal, and metabolic systems. Its central mechanisms include visceral adiposity, insulin resistance, adipokine imbalance, chronic low-grade inflammation (metaflammation), and oxidative stress \cite{1, 2}. This pathological background contributes to the development of acute myocardial infarction (AMI) through endothelial dysfunction, reduced nitric oxide (NO) bioavailability, impaired microvascular perfusion, and destabilization of atherosclerotic plaques. In patients with CRMS, AMI differs from the classical ischemic model, as it is characterized not only by impaired coronary blood flow but also by an intense inflammatory response, activation of the immune system, and disturbances in cellular energy metabolism. During the early phase of infarction, damage-associated molecular patterns (DAMPs) activate Toll-like receptors, initiating the NF-κB signaling pathway and increasing the production of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Furthermore, mitochondrial dysfunction and excessive generation of reactive oxygen species (ROS) amplify oxidative stress, promoting lipid peroxidation, DNA damage, and cardiomyocyte apoptosis. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors, particularly dapagliflozin, have attracted considerable attention as agents with broad cardiorenometabolic benefits. Their therapeutic effects are multifaceted and extend well beyond glycemic control. SGLT2 inhibitors exert cardioprotective effects by suppressing inflammatory signaling pathways (NF-κB and the NLRP3 inflammasome), reducing oxidative stress, restoring mitochondrial function, inhibiting the sodium-hydrogen exchanger-1 (NHE1), and decreasing intracellular calcium overload in cardiomyocytes \cite{9, 12}. This review systematically analyzes the role of SGLT2 inhibitors in the pathogenesis of AMI, their molecular, cellular, and systemic mechanisms of action, and their cardiorenometabolic efficacy based on evidence from contemporary clinical studies, including the DAPA-MI (Dapagliflozin in Myocardial Infarction) trial.
Keywords
List of references
-
Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606-1635. https://doi.org/10.1161/CIR.0000000000001184.
-
Khan SS, Ning H, Wilkins JT, et al. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic Syndrome. Circulation. 2023;148(20):1636-1664. https://doi.org/10.1161/CIR.0000000000001186.
-
American Diabetes Association Professional Practice Committee. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S216-S249.
-
American Diabetes Association Professional Practice Committee. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S246-S265.
-
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4 Suppl):S117-S314. https://doi.org/10.1016/j.kint.2023.10.018.
-
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381:1995-2008. https://doi.org/10.1056/NEJMoa1911303.
-
Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383:1436-1446. https://doi.org/10.1056/NEJMoa2024816.
-
Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes: a systematic review and meta-analysis. Lancet. 2019;393(10166):31-39. https://doi.org/10.1016/S0140-6736(18)32590-X.
-
Lee TM, Chang NC, Lin SZ. Dapagliflozin inhibits inflammation via suppression of the NLRP3 inflammasome. Cardiovasc Diabetol. 2021;20:1-14. https://doi.org/10.1186/s12933-021-01385-2.
-
Yang L, Wu Y, Wang Y, et al. SGLT2 inhibitors attenuate inflammation via NF-κB signaling pathways. Front Endocrinol. 2022;13:992937. https://doi.org/10.3389/fendo.2022.992937.
-
Abdollahi E, Keyhanfar F, Delbandi AA, et al. Dapagliflozin exerts anti-inflammatory effects via TLR4/NF-κB pathway. Eur J Pharmacol. 2022;921:174607. https://doi.org/10.1016/j.ejphar.2022.174607.
-
Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit. Circulation. 2018;137(4):405-407. https://doi.org/10.1161/CIRCULATIONAHA.117.030012.
-
Santos-Gallego CG, Garcia-Ropero A, Mancini D, et al. Metabolic effects of SGLT2 inhibition on cardiac metabolism. J Am Coll Cardiol. 2019;73(15):1931-1944. https://doi.org/10.1016/j.jacc.2019.02.027.
-
Packer M. Critical review of mechanisms underlying the cardiorenal benefits of SGLT2 inhibitors. JACC Heart Fail. 2020;8(5):354-363. https://doi.org/10.1016/j.jchf.2020.02.006.
-
Lee TM, Chang NC, Lin SZ. Dapagliflozin reduces cardiac fibrosis and remodeling. Cardiovasc Diabetol. 2021;20:1-14. https://doi.org/10.1186/s12933-021-01385-2.
-
Berg DD, Jhund PS, Docherty KF, et al. Dapagliflozin in patients after acute myocardial infarction (DAPA-MI trial). Circulation. 2023. https://doi.org/10.1161/CIRCULATIONAHA.123.067444.
-
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347-357. https://doi.org/10.1056/NEJMoa1812389.
About the Authors
License
Copyright (c) 2026 Sayyora Z.Aliyeva,Nigora Z.Srojidinova (Muallif)
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
