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

The mechanism behind the reductions in risk of cardiovascular disease and all-cause mortality seen during SGLT2-inhibitor treatment is not fully understood. We examined potential mediators of these effects using a functional genetic variant in the gene encoding SGLT2, a variant that mimics the effect of pharmacological SGLT2-inhibition regarding reductions in risk of cardiovascular disease and mortality in the general population and found that the beneficial effects were at most modestly mediated by changes in plasma glucose. Our results support that SGLT2-inhibitors may reduce risk of cardiovascular disease and all-cause mortality in individuals with and without diabetes in the general population.