EPAS1 and diabetes mellitus: in diabetes.15 And SGLT2is mimic fasting, activating cellular nutrient deprivation signals, dampening stress and inflammation pathways, underlying the stimulation of sirtuin-1 (SIRT-1) and heme oxygenase-1.539 Then, reduced inflammation-related hepcidin and ferritin expression elevates reactive ferrous iron (Fe2+), promoting SIRT1’s activation on HIF-2α in the liver and kidney, while while reducing HIF-1α in the kidney.