Sodium-Glucose Cotransporter 2 Inhibitors and Changes in Epicardial Adipose Tissue: A Systematic Literature Review And Meta-Analysis

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk. Aims: This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT. Methods: We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up. Results: The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial betweenstudy heterogeneity (I2: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger’s regression test did not indicate the presence of publication bias Conclusion: This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.