Diabetes Obes MetabHeart & CardiovascularNovember 27, 2025

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

Heuboeck E, Bhogal CS, Mandl M

Key Finding

SGLT-2 inhibitors and GLP-1 receptor agonists most consistently transform dangerous heart fat (epicardial adipose tissue) from inflammatory troublemaker to metabolic helper, reducing thickness and promoting healthy fat browning.

What This Study Found

Think of epicardial adipose tissue (EAT) as your heart's next-door neighbor - a layer of fat that sits right between your heart muscle and the protective sac around it. When you're healthy, this fat neighbor is actually helpful, supplying energy to your heart and helping regulate temperature like a good friend bringing over groceries and adjusting your thermostat. But when obesity, diabetes, or heart problems develop, this neighbor turns toxic - growing bigger, becoming inflamed, and sending harmful signals that damage your heart muscle and blood vessels, like a neighbor who stops maintaining their yard and starts throwing trash over the fence. Among various diabetes and heart medications tested (statins, PPAR-gamma drugs, AMPK activators, GLP-1 agonists, and SGLT-2 inhibitors), the SGLT-2 inhibitors and GLP-1 receptor agonists emerged as the most reliable 'neighborhood mediators.' These drugs consistently help transform the problematic fat back into helpful fat by reducing its thickness, cooling down inflammation, improving insulin sensitivity, and promoting 'browning' - essentially converting lazy white fat cells into more active brown fat cells that burn energy efficiently, like convincing a troublesome neighbor to become a model citizen who actually improves the whole block.

Statistics Decoded

This abstract is a review paper summarizing existing research rather than presenting new statistical data. The authors evaluated multiple drug classes and found that SGLT-2 inhibitors and GLP-1 receptor agonists showed 'the most consistent effects' - meaning across multiple studies, these two drug types reliably produced beneficial changes in heart fat, while other medications showed more variable or less pronounced effects. The review doesn't provide specific numerical outcomes but synthesizes patterns from 'in vitro and in vivo studies' - meaning both laboratory cell studies and animal/human studies.

Why This Matters

This matters because it reveals a previously underappreciated way that GLP-1 and SGLT-2 diabetes drugs protect the heart - not just through blood sugar control, but by directly remodeling dangerous heart fat into healthy, metabolically active tissue that supports rather than harms cardiac function.

Original Abstract

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.