As a result, the reasons for the beneficial cardiovascular effects are not yet clear, however recently suggested theories include: (i) SGLT2 inhibitor induced plasma volume contraction (5% increase in haematocrit in conjunction with a 35% relative risk reduction in hospital admission for HF on empaliflozin arm) (118); (ii) Restoring cellular energy homeostasis by activation of AMPK (119, 120); (iii) SGLT2 inhibitor induced mild ketosis (121, 122). The gene discussed is SLC5A2; the disease is hydrops fetalis.