Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome

作者：Jiaxin Hua, Qingyuan Wang, Ye Liu, Shengwei Luo, Ao Shi, Zhiwei Yan, Jing Zhang, Wenli Gu, Lihan Zhu, Yuling Zhang, Liang Zhang, Peng Yu, Xiao Liu, Wenting Wang · 发表于：Cardiovascular Diabetology · 年份：2026 · DOI：10.1186/s12933-026-03173-5 · 被引用次数：1 · 研究领域：Diabetes Treatment and Management、Chronic Kidney Disease and Diabetes、Liver Disease Diagnosis and Treatment

The escalating global burden of chronic multimorbidity has necessitated a fundamental transition from organ-centric treatment models toward integrated, multisystemic management strategies. Central to this evolution is the recognition of the cardiovascular–kidney–liver-metabolic (CKM) syndrome, a clinical framework arising from the profound and bidirectional pathophysiological crosstalk between metabolic dysfunction, chronic kidney disease, and heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have transitioned from simple glucose-lowering drug to a critical pillar of the area of cardiovascular metabolism, demonstrating profound benefits across the cardiovascular, metabolism and renal systems. These therapeutic effects are driven by a complex interplay of hemodynamic and non-hemodynamic mechanisms, including the restoration of tubuloglomerular feedback, optimization of myocardial energetics, and the attenuation of systemic inflammation and oxidative stress. This pharmacological profile aligns precisely with the multi-stage progression of CKM syndrome, offering a cohesive intervention to interrupt the vicious cycle of systemic risk. In this review, we delineated the mechanistic pathways by which SGLT-2i modulate the CKM axis and evaluate the clinical evidence supporting its important role for integrated CKM management, providing a comprehensive perspective on optimizing long-term outcomes through multisystemic targeting.