Genetic variation in SLC5A2 mimicking SGLT2-inhibition and risk of cardiovascular disease and all-cause mortality: Reduced risk not explained by lower plasma glucose

Background and Aims: Treatment with sodium-glucose co-transporter 2(SGLT2)-inhibitors reduces risk of cardiovascular disease and all-cause mortality, but the mechanism is unclear. We hypothesized that a functional genetic variant in SLC5A2, known to be associated with familial renal glucosuria, would mimic pharmacological SGLT2-inhibition and thus provide an opportunity to examine potential mediators of the effects on lower risk of cardiovascular disease and all-cause mortality.