Association between body mass index reduction and epicardial adipose tissue changes across pharmacological and lifestyle interventions: a multilevel meta-regression analysis

Abstract Background Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot implicated in cardiometabolic disease. Although EAT reductions are commonly attributed to weight loss, the extent to which EAT change is explained by body mass index (BMI) reduction versus intervention-specific effects remains unclear. Methods We performed a systematic review and multilevel meta-regression of interventional studies reporting pre- and post-intervention changes in EAT and BMI. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to April 2026. Standardized mean change using pre-test standardization (SMCR) was calculated for both outcomes. Multilevel meta-regression assessed the association between BMI and EAT change while adjusting for intervention class, follow-up duration, and imaging modality. BMI-adjusted residual analyses were used descriptively to evaluate deviations from model-predicted EAT responses. Results Forty-two studies comprising 50 intervention arms and 1,890 participants were included. Across all interventions, both EAT and BMI decreased significantly. In the multivariable meta-regression model, BMI reduction was associated with EAT reduction (β = 0.19, p = 0.03), although BMI explained only a limited proportion of variability in EAT response. Intervention class remained a significant moderator of EAT change ( p < 0.001). Larger observed reductions in EAT were seen with dietary interventions, GLP-1 receptor agonists, and bariatric surgery. In descriptive residual analyses, dietary interventions and GLP-1 receptor agonists demonstrated greater-than-predicted reductions in EAT relative to the overall study-level BMI–EAT relationship. These findings should be interpreted cautiously because intervention-specific comparisons were exploratory and do not constitute formal comparative efficacy estimates. Discussion EAT reduction is only partially explained by systemic weight loss, and substantial heterogeneity exists across intervention classes. These findings support the concept that EAT remodeling may be influenced by factors beyond generalized adiposity reduction. However, intervention-specific patterns observed in this study are descriptive and hypothesis-generating and require confirmation in adequately powered comparative studies. Moreover, overall certainty of evidence was low for pooled EAT reduction and very low for intervention-specific comparative patterns. Trial registration PROSPERO (CRD420261367140).