Although most compounds targeting the PI3K/Akt pathway – such as estrogen [114], resveratrol, curcumin [115], GDC-0941, duvelisib, and leniolisib [112] – have already entered clinical trials for other diseases (oncology, metabolic disorders, and neurodegenerative diseases), their clinical application in sepsis, especially SAE, remains largely unexplored or is still in its infancy. This evidence concerns the gene AKT1 and metabolic disease.