Understanding the protective effects of SGLT2 inhibitors in type 2 diabetes patients with chronic kidney disease

Sodium-glucose co-transporter type 2 inhibitors (SGLT2is) were developed as glucose-lowering agents for the management of type 2 diabetes (T2D). Unexpectedly, they showed a significant reduction in hospitalization for heart failure and hard renal outcomes in patients with and without T2D. Underlying mechanisms remain a matter of debate.We summarize the protective renal effects of SGLT2is in patients with cardiovascular disease, chronic kidney disease (CKD, especially with albuminuria) or heart failure; a description of the safety of SGLT2is, with a special focus on the risk/benefit balance in people with stage 3 CKD; a comprehensive discussion of mechanisms that could explain nephro-protection; a reappraisal of the positioning of SGLT2is in recent international guidelines.Several mechanisms could contribute to improved renal prognosis with SGLT2is, among which a reduction in intraglomerular pressure by restoring the tubuloglomerular feedback, a diuretic effect that contributes to lower albuminuria and renal decongestion, especially if fluid overload is present, a reduction in renal oxygen consumption, an improvement of heart failure status with less cardiorenal syndrome and a lower risk of acute renal injury. All these effects may be mutually not exclusive, and their respective contribution may differ according to patient characteristics.