SGLT2 inhibitors are associated with reductions in epicardial adipose tissue volume and thickness: a meta-analysis

BACKGROUND: Epicardial adipose tissue (EAT), a metabolically active fat depot surrounding the myocardium, is implicated in the pathogenesis of cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated cardioprotective effects beyond glucose lowering, including a modification of EAT. We performed a systematic review and meta-analysis to evaluate the effect of SGLT2i on serial EAT measurement. METHODS: A comprehensive search of PubMed, Medline, EMBASE, Cochrane Library and grey literature (English only, 2000-2025) was performed for studies assessing EAT pre- and post-SGLT2i treatment, or SGLT2i vs conventional therapy, using computed tomography, echocardiography, or cardiac magnetic resonance. Data were meta-analysed using random-effects models with standardised mean differences (SMD) as summary effects. RESULTS: A total of 11 studies, including 284 patients, were included (89 with echocardiographic EAT thickness assessment and 195 with volumetric measurement using CT or CMR). In analyses comparing SGLT2 inhibitors with conventional antidiabetic therapy, treatment was associated with a significant reduction in EAT (Hedges g - 1.64, 95% CI -2.10 to -1.18; p < 0.01). In exploratory within-group analyses, SGLT2 inhibitor therapy was associated with a reduction in EAT from baseline to follow-up (Hedges g - 0.62, 95% CI -0.88 to -0.36; p < 0.01). On modality-specific subgroup analysis, reductions were observed in both EAT thickness (echocardiography) (Hedges g - 0.74, 95% CI -1.05 to -0.43; p < 0.01) and EAT volume (CT/CMR) (Hedges g - 0.54, 95% CI -0.90 to -0.18; p < 0.01), with no significant difference between modalities (p = 0.32 for interaction). SGLT2 inhibitor therapy was also associated with modest reductions in body mass index (Hedges g - 0.23, 95% CI -0.43 to -0.03; p = 0.03) and systolic blood pressure (Hedges g - 0.32, 95% CI -0.59 to -0.05; p = 0.02). Exploratory subgroup analyses suggested larger reductions in EAT in studies evaluating dapagliflozin compared with empagliflozin; however, this indirect comparison was based on a small number of heterogeneous studies and should be considered hypothesis-generating only. CONCLUSIONS: SGLT2i significantly reduces EAT volume and thickness, which may contribute to their broad cardiovascular benefits. Targeting EAT may represent a novel therapeutic approach for mitigating cardio-metabolic risk. STUDY REGISTRATION: PROSPERO CRD42024621242 SGLT2 inhibitor therapy is associated with reduced epicardial adipose tissue (EAT) across multimodality imaging (Hedges g -0.62), with consistent effects on both thickness and volume. Modest reductions in body mass index and systolic blood pressure were also observed, alongside improvements in inflammatory and metabolic markers.