Dapagliflozin reduces epicardial adipose tissue in patients with heart failure and type 2 diabetes

Abstract Background Epicardial adipose tissue (EAT) has a contributory role in the progression of heart failure. We tested whether dapagliflozin reduces EAT in adults with type 2 diabetes (T2D) and heart failure and explored links with systemic inflammation and cardiac structure. Methods This analysis is based on pooled data from two phase 2, single‐centre, double‐blind, placebo‐controlled randomised trials (REFORM and DAPA‐LVH) conducted in Scotland. Exactly 122 participants with T2D and stage B or C heart failure were randomised to dapagliflozin 10 mg once daily or placebo for 12 months. Cardiac magnetic resonance imaging (CMR) was used to assess EAT. At baseline and follow‐up, the inflammatory markers TNF, IL‐1, IL‐6, IL‐10, and CRP were measured. Results At baseline, obesity was common (75% with BMI ≥30 kg/m 2 ) and heart‐failure phenotypes were balanced (HFpEF 51%, HFrEF 49%). After 12 months, dapagliflozin significantly reduced EAT independently of changes in BMI (−1.16 ± 0.18 vs. +0.36 ± 0.19 cm 2 , p < 0.001), BMI (−1.17 ± 0.16 vs. −0.18 ± 0.17 kg/m 2 , p < 0.001), and left ventricular mass (−3.53 ± 1.77 vs. +1.57 ± 1.83 g, p = 0.048) compared with placebo. Conclusion Dapagliflozin shrinks EAT and LV mass independently of BMI in T2D patients with stage B/C heart failure, supporting EAT as a modifiable target of SGLT2 inhibition. The absence of parallel changes in systemic inflammation suggests primarily local mechanisms.