Among the studies included in the present meta-analysis, only canagliflozin caused a significant reduction in the incidence of MACE in the obesity sub-group of CREDENCE and CANVAS, while other SGLT-2 inhibitors did not13,14,16–18, and hypotheses have been proposed to explain this inconsistency in the effects of SGLT-2 inhibitors on the incidence of MACE34. This evidence concerns the gene SLC5A2 and obesity due to melanocortin 4 receptor deficiency.