Cardiometabolic disease is increasingly shaped by the overlap among obesity, type 2 diabetes, chronic kidney disease, heart failure, and atherosclerotic cardiovascular disease, underscoring the need for prevention strategies that extend beyond glucose-centered care. This narrative review critically examines the mechanistic rationale, clinical evidence, guideline evolution, and practical implementation of sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) within the cardiorenal-metabolic continuum. A structured literature search was conducted in PubMed, Scopus, and Web of Science, focusing primarily on publications from January 2019 to March 2026, with selected landmark studies from earlier years included for context. Priority was given to randomized controlled trials, major cardiovascular and kidney outcome trials, meta-analyses, clinical practice guidelines, scientific statements, and expert consensus documents. The reviewed evidence indicates that SGLT-2 inhibitors show the most consistent benefits in reducing heart failure events, slowing chronic kidney disease progression, and lowering cardiorenal risk, whereas GLP-1 receptor agonists are more strongly associated with reductions in major adverse cardiovascular events, residual atherosclerotic risk, and body weight. Emerging data also support extension of this therapeutic paradigm beyond diabetes, particularly in obesity-associated cardiovascular risk. Contemporary care is increasingly moving toward phenotype-informed treatment selection, earlier organ-protective intervention, and multidisciplinary management, although cost, access, tolerability, and implementation barriers remain important limitations. SGLT-2 inhibitors and GLP-1 receptor agonists are therefore central to modern cardiovascular prevention across the cardiovascular-kidney-metabolic spectrum. In this context, the proposed Cardiometabolic 2.0 framework may serve as a clinically oriented model for integrating these therapies within contemporary organ-protective care.
