Heart matters: How glucose‐ and lipid‐modulating drugs remodel epicardial adipose tissue accumulation, inflammatory patterns and browning

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot located between the myocardium and the visceral pericardium, exerting direct paracrine and vasocrine effects on the heart and coronary vessels. Under physiological conditions, EAT supports myocardial energy metabolism and thermoregulation through fatty acid supply and adaptive metabolic flexibility. In cardiometabolic disorders such as obesity, type 2 diabetes, and heart failure, EAT undergoes pathological remodelling characterized by increased thickness, adipocyte hypertrophy, immune cell infiltration, and secretion of pro-inflammatory and fibrotic mediators. These alterations contribute to myocardial fibrosis, stiffness, and coronary atherosclerosis, particularly in heart failure with preserved ejection fraction. Pharmacological modulation of EAT has therefore emerged as a promising therapeutic approach in cardiovascular prevention. Agents such as statins, peroxisome proliferator-activated receptor gamma agonists, adenosine monophosphate-activated protein kinase activators, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors exert both systemic and depot-specific effects. They reduce EAT thickness, suppress inflammatory signalling, enhance insulin sensitivity, and promote adipocyte browning and oxidative metabolism. Among these, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists show the most consistent effects in shifting EAT towards a less inflammatory and more metabolically active phenotype. The goal of this review is to provide an overview of current pharmacological interventions that influence EAT and to summarize how much is known about their molecular mechanisms from in vitro and in vivo studies. The target audience includes cardiovascular researchers and clinicians seeking to better understand how metabolic and antidiabetic therapies modulate cardiac fat biology and function.