SGLT2i up-regulated sirtuins and improved cardiac function by enhancing autophagic flux in a murine doxorubicin-induced cardiomyopathy model.189 AMPK, which acts as an energy sensor, inhibits several ATP-consuming biosynthetic pathways when ATP level is low to promote energy restoration.190 SGLT2i therapy simultaneously increases AMPK phosphorylation (activation)185 and decreases mTOR phosphorylation,191 leading to improved heart function in HF. This evidence concerns the gene MTOR and hydrops fetalis.