HIF1A and heart failure: Moreover, the sodium/glucose cotransporter 2 inhibitor (SGLT2i) is now the only medication that covers the full range of heart failure care, thanks to its potential for cardiac regeneration.500,538 High glucose, advanced glycation end products (AGEs), mTOR, and hypoxia overactivate HIF-1α, while SIRT1 suppression downregulates HIF-2α.