Background and Objectives: Dapagliflozin treatment proved to reduce the epicardial fat volume (EFV) in patients with type 2 diabetes (T2D). Despite the reduction in EFV being associated with improved diastolic function in patients with T2D, EVF is not routinely evaluated in T2D because it is costly and involves radiation exposure. This study aims to identify biomarkers that predict EFV reduction after dapagliflozin treatment in patients with T2D. Materials and Methods: In a prospective, observational, consecutive-case enrollment scenario, 52 patients with T2D were initiated on dapagliflozin 10 mg q.d. as part of the standard of care. At enrollment and after six months of dapagliflozin treatment, patients were evaluated using cardiac ultrasonography, native computer tomography, transient liver elastography, and metabolic lab tests. In addition, the atherogenic index of plasma (AIP), atherogenic coefficient (AC), triglyceride glucose index (TyG), cardiac risk ratio (CRR), and visceral abdominal index (VAI) were calculated. Results: Higher AIP (r = 0.28; p = 0.04), CRR (r = 0.28; p = 0.04), and TyG (r = 0.32; p = 0.01) are associated with more important reductions in the EFV. A lower conicity index (ß = -0.29; p = 0.03), visceral fat volume at the 4th vertebrae (L4VFV) (ß = -0.32; p = 0.02), left atrium volume (ß = -3.08; p = 0.003), and right ventricle diameter (ß = -2.13; p = 0.04) are associated with higher reductions in the EFV after six months of dapagliflozin treatment. A valid performance for predicting clinically relevant decreases in EFV after dapagliflozin treatment was observed for AIP (AUROC = 0.903; Youden = 0.732; p < 0.001), CRR (AUROC = 0.772; Youden = 0.595; p = 0.004), TyG (AUROC = 0.957; Youden = 0.904; p < 0.001), and VAI (AUROC = 0.898; Youden = 0.712; p < 0.001). Conclusion: Higher initial EFV values are associated with more important reductions in EFV in patients with T2D treated for six months with dapagliflozin. TyG values have the best prediction performances for EFV reduction, having the highest sum of sensitivity and specificity at the 0.904 threshold level. AIP, CRR, VAI, conicity index, L4VF, left atrium volume, and right ventricle volume are valid biomarkers for a decrease in EFV after dapagliflozin treatment in diabetes patients.