For MACE, there is no class effect, as the 7% reduction of MACE risk observed in DECLARE [11] was not significant (HR = 0.93, 95% confidence interval, 0.84–1.03, P = 0.17); on the other hand, a class effect is evident for both hospitalization for heart failure and progression of DKD, as in all four trials the risk of HF and DKD progression was significantly reduced by all SGLT-2 inhibitors. This evidence concerns the gene SLC5A2 and diabetic kidney disease.