André J Scheen
Type 2 diabetes (T2D) is strongly associated with an increased risk of cardiovascular disease, chronic kidney disease, heart failure, and metabolic dysfunction-associated steatotic liver disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated significant benefits in improving outcomes among patients with T2D who are at risk of these complications. Emerging clinical evidence indicates that these benefits extend beyond glycemic control and are largely independent of baseline glucose levels. SGLT2is exert pleiotropic effects that encompass a wide range of metabolic, hormonal, hemodynamic, biochemical, and anti-inflammatory actions, each potentially contributing to improved clinical outcomes. However, the relative importance of these mechanisms remains debated and likely varies according to the specific complication targeted-whether atherosclerotic cardiovascular disease, chronic kidney disease, or heart failure. This comprehensive review aims to provide an updated overview of the major chronic metabolic effects of SGLT2is, with particular emphasis on those mechanisms that may contribute to improved prognosis in individuals with T2D.