Background <p>Heart failure with preserved ejection fraction is the fastest-growing subtype of heart failure, especially among the elderly.</p> Aim <p>It is aimed to determine whether the addition of 10&#xa0;mg of Dapagliflozin for HFpEF patient can lead to a decrease in epicardial adipose tissue volume.</p> Methods <p>this non-randomized clinical trial included 60 patients presented with left ventricular diastolic dysfunction (30 patients fulfilling HFpEF diagnostic criteria received dapagliflozin 10&#xa0;mg once daily in addition to standard medical therapy and 30 patients with LV diastolic dysfunction who did not meet HFpEF criteria received standard medical care only).</p> Results <p>The mean EAT volume was significantly (<i>p</i> &lt; 0.001) higher in the HFpEF + dapagliflozin group vs. standard care group at baseline while it was comparable in the two groups at follow-up (<i>p</i> = 0.081). For within group comparisons, insignificant (<i>p</i> = 0.124) change was recorded for the standard care group while there was significant reduction in the HFpEF + dapagliflozin arm (<i>p</i> &lt; 0.001). Additionally, EAT reduction in the HFpEF + dapagliflozin group was confirmed by the interaction between time and treatment modality (<i>p</i> &lt; 0.001).</p> Conclusions <p>SGLT2 inhibitor use was associated with a significant reduction in epicardial adipose tissue, a fat depot implicated in HFpEF pathophysiology. This finding suggested a possible structural association that warrants confirmation in randomized out-come driven trials.</p> Trial registration <p>NO. (NCT06510270) (first submitted date 15/7/2024, first posted date 19/7/2024)</p>