Translating localized renal reprogramming to systemic protection: A comprehensive review of SGLT2 inhibitors in cardiovascular-kidney-metabolic syndrome

Cardiovascular-kidney-metabolic syndrome is a multifaceted condition encompassing chronic kidney disease, end-stage renal disease, and cardiovascular diseases stemming from underlying cardiometabolic disorders. Sodium-glucose co-transporter 2 inhibitors, an innovative category of hypoglycemic agents, are increasingly recognized for their profound therapeutic efficacy in managing this complex syndrome. The primary objective of this review is to comprehensively evaluate the impact of SGLT2 inhibitors on the interconnected pathways that contribute to type 2 diabetes mellitus and its systemic cardiovascular and renal consequences. While the precise mechanisms of SGLT2 inhibitors are still not fully understood, several plausible pathways have been proposed and are supported by robust experimental and clinical data. Current literature indicates that these agents provide substantial multi-organ protection; they enhance metabolic profiles, decelerate the progression of chronic kidney disease, and significantly decrease cardiovascular mortality in individuals with and without diabetic comorbidities. Ultimately, subsequent investigations must focus on identifying the specific patient populations most likely to benefit from this intervention and optimizing targeted treatment regimens to further enhance clinical outcomes.