Almost certainly it is a multi-factorial combination of mechanisms that contribute to the pathophysiology of CVD and CKD in T2D including the metabolic and haemodynamic abnormalities described above, together with other mechanisms such as lipotoxicity and oxidative stress; it is likely that their improvement/reversal explains the clinical benefits of SGLT2 inhibitors. This evidence concerns the gene SLC5A2 and type 2 diabetes mellitus.