Cardiovascular protection by SGLT2 inhibitors: an integrative review of mechanistic networks, clinical evidence, and safety considerations
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors were originally developed as glucose-lowering agents for type 2 diabetes mellitus, but accumulating evidence has demonstrated their broad cardiovascular and cardiorenal benefits beyond glycemic control. In particular, empagliflozin and dapagliflozin have shown robust prognostic benefits in heart failure with reduced ejection fraction (HFrEF) and expanding therapeutic value in heart failure with preserved ejection fraction (HFpEF). However, their cardiovascular protection cannot be fully explained by glucose lowering alone and is likely mediated through a multilayered network of systemic, metabolic, vascular, and cellular mechanisms. This integrative narrative review summarizes current mechanistic and clinical evidence regarding SGLT2 inhibitors in cardiovascular disease and proposes a translational framework linking hemodynamic rebalancing, cardiometabolic reprogramming, vascular protection, redox homeostasis, mitochondrial quality control, immunometabolic modulation, and attenuation of adverse myocardial remodeling. Clinically, the strongest evidence has been established in heart failure, whereas data in ischemic heart disease, post-myocardial infarction remodeling, and arrhythmias remain promising but less definitive. In post-myocardial infarction settings, SGLT2 inhibitors may improve N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, ventricular remodeling parameters, and heart failure-related outcomes,…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.