Frontiers in Endocrinology · Oct 30, 2026
Hypertensive type 2 diabetes across the cardio-renal-hepatic-metabolic continuum: a precision-medicine framework for therapeutic decision-making
By Christiano Argano, Rosario Scaglione, Salvatore Corrao
Hypertension and type 2 diabetes (T2D) frequently coexist and amplify cardiovascular, kidney, and hepatic risk through overlapping hemodynamic, metabolic, inflammatory, and fibrotic pathways. This review positions hypertensive T2D within the established cardiovascular-kidney-metabolic (CKM) framework and uses a cardio-renal-hepatic-metabolic (CRHM) extension to make metabolic dysfunction-associated steatotic liver disease (MASLD) explicit. We synthesize evidence across pathophysiology, phenotyping, organ-protective therapy, risk stratification, and decision support. This narrative review is based on a structured but non-systematic literature search and does not include a formal risk-of-bias assessment or grading of evidence certainty. Clinically relevant heterogeneity is organized around dominant phenotypes—albuminuric or nonalbuminuric chronic kidney disease, heart failure or volume overload, atherosclerotic cardiovascular disease, obesity/MASLD, and resistant or nocturnal hypertension—rather than glycemic control alone. Current trial and guideline evidence supports layered use of renin-angiotensin system blockade, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1–based therapies, and finerenone according to kidney, cardiovascular, adiposity, and albuminuria profiles, alongside intensive risk-factor control and lifestyle treatment. Emerging biomarkers, multi-omics, imaging, and machine learning may refine risk and treatment-effect estimation, but most remain insufficiently validated for routine prescriptive use. A precision-medicine framework therefore requires a hierarchy of evidence: guideline-directed organ protection first, phenotype-based intensification second, and investigational molecular or artificial-intelligence tools as adjuncts until externally and prospectively validated.