LAUSR

Sodium–glucose co-transporter 2 inhibitors (SGLT2i) were developed as oral hypoglycemic agents to control hyperglycemia in patients with type 2 diabetes mellitus (T2DM), but the results of several large randomized controlled trials over the past decade have revealed that they do much more than reduce hyperglycemia and have substantial favorable cardiometabolic effects [1–12]. In this issue, Qiu et al. [13] report on a meta-analysis of ten cardiovascular outcomes trials (CVOTs) with five SGLT2i to highlight their broad actions in controlling and managing multiple cardio-metabolic perturbations. They showed that treatment with SGLT2i was associated with substantial benefits in multiple cardiometabolic and renal endpoints [13]. The authors provided detailed analyses in the paper but did not discuss the mechanistic aspects of the results observed with SGLT2i or provide information about the reasons for differences observed in their included trials. Accordingly, it will be advantageous to briefly review the mechanisms of action of SGLT2i and the findings of the major CVOTs to fully understand and put into perspective the findings described by Qiu et al. [13].