Gliflozines use in heart failure patients. Focus on renal actions and overview of clinical experience

Use of type 2 sodium-glucose cotransporter inhibitors (SGLT2i) gliflozines have first been applied to treatment of diabetic patients. In this setting, unexpected benefits on concomitant heart failure (HF) were seen in large trials. This clinical benefit was initially traced back to their natriuretic properties and as such they were also included in the therapeutic armamentarium of HF treatment. However, further insight into their mechanism of action has clarified their complex interaction with kidney function which better explains their prompt effectiveness in ameliorating HF outcome in the long-term, independent of left ventricular ejection fraction (LVEF) phenotype and concomitant presence of diabetes and/or chronic renal disease. This mainly results from the ability of SGLT2i to counteract the HF-associated hyperactivity of the sympathetic system and neurohormonal activation by modifying the pattern of renal tubular sodium and glucose reabsorption which results in curbing the overall sodium reabsorption. Their action results in decreased kidney workload and related oxygen consumption thus indirectly reducing sympathetic activity. The complex renal functional changes associated with HF and their modifications during SGLT2i administration will be reviewed.