In the past decade, the therapeutic scope of sodium–glucose cotransporter 2 (SGLT2) inhibitors has expanded beyond glycaemic regulation in the management of type 2 diabetes mellitus. In this Review, Lim et al. discuss data from clinical studies of SGLT2 inhibitors, demonstrating their multifaceted cardiovascular, metabolic and renal effects, and elucidate the diverse mechanisms underpinning these benefits.