Diabetic Cardiomyopathy: Recent Advances in Pathophysiology, Clinical Phenotypes, Diagnostic Approaches and Emerging Therapeutic Strategies: A Comprehensive Review

Abstract

Diabetes mellitus is now recognized as a significant and independent contributor to myocardial disease, extending well beyond its established role in coronary artery disease. Diabetic cardiomyopathy (DCM) refers to structural and functional abnormalities of the myocardium that result from diabetes itself, diagnosed once other major causes such as significant coronary artery disease or valvular disease have been reasonably excluded. The condition typically develops gradually. Early metabolic disturbances and subclinical myocardial changes often precede diastolic dysfunction, ventricular hypertrophy, and fibrosis, and in some patients this progresses further to systolic dysfunction and overt clinical heart failure (Dillmann, 2019; Huo et al., 2023). At the cellular level, chronic hyperglycemia and insulin resistance alter how the heart utilizes metabolic substrates. This promotes glucotoxicity, lipotoxicity, mitochondrial dysfunction, oxidative stress, low-grade inflammation, abnormal calcium handling, endoplasmic reticulum stress, and eventual loss of cardiomyocytes. These changes are further compounded by the accumulation of advanced glycation end products, overactivation of the renin-angiotensin-aldosterone system, endothelial and microvascular dysfunction, cardiac autonomic neuropathy, and remodeling of the extracellular matrix, all of which add to the overall burden of myocardial injury (Jia et al., 2018; Tan et al., 2020). Advances in cardiac imaging have made it possible to detect these abnormalities at an earlier stage than was previously achievable. Strain-based echocardiography and cardiac magnetic resonance imaging can now identify myocardial dysfunction well before any measurable decline in conventional left ventricular ejection fraction occurs (Huo et al., 2023; Tadic et al., 2025). This allows for the possibility of earlier clinical intervention. As a result, the management of DCM can no longer be limited to glycemic control alone. It requires a broader approach that includes comprehensive cardiovascular risk reduction along with evidence-based heart failure therapy. Sodium-glucose cotransporter-2 inhibitors have shown clear and clinically meaningful benefit across the different phenotypes of heart failure. Glucagon-like peptide-1 receptor agonists, along with newer dual incretin-based therapies, are also gaining importance, particularly in patients with obesity-related and cardiometabolic forms of heart failure with preserved ejection fraction (American Diabetes Association Professional Practice Committee, 2026). This review outlines the biological basis, clinical progression, diagnostic approach, and current as well as emerging treatment strategies for diabetic cardiomyopathy. It also highlights the ongoing gap between the strong mechanistic and experimental evidence regarding the same.

Keywords: Diabetic Cardiomyopathy, Diabetes Mellitus, Myocardial Fibrosis, Oxidative Stress, Mitochondrial Dysfunction, Lipotoxicity, Heart Failure, SGLT2 Inhibitors, GLP-1 Receptor Agonists