Evolving understanding of cardiovascular protection by SGLT2 inhibitors: focus on renal protection, myocardial effects, uric acid, and magnesium balance.

Robust clinical data indicate that inhibitors of the sodium/glucose cotransporter 2 (SGLT2) dramatically improve clinical outcomes in diabetes, especially heart failure and progression of kidney disease. Factors that may contribute to these findings include: 1) improved glycemic control, 2) diuresis and reduced extracellular fluid volume, 3) reduced serum uric acid levels, 3) direct myocardial effects, 4) reduction in proteinuria and preservation of kidney function, and 5) correction of diabetic magnesium deficiency. Understanding the mechanisms by which SGLT2 inhibitors improve cardiovascular outcomes has the potential to improve clinical management not only of diabetes, but also of other cardiovascular disorders such as heart failure and chronic kidney disease.