Extending the ambit of SGLT2 inhibitors beyond diabetes: a review of clinical and preclinical studies on non-diabetic kidney disease

INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic agents with overwhelming cardiorenal protection. Recent trials focusing on the nephroprotective role of SGLT2i have underscored its success as a phenomenal agent in halting the progression of kidney disease in patients with and without Type 2 diabetes mellitus. Multitudes of pleiotropic effects on tubules have raised hopes for reasonable nephroprotection beyond the purview of the hyperglycemic milieu. AREA COVERED: This review summarizes various animal and human data as evidence for the utility of SGLT2i in non-diabetic chronic kidney disease (CKD). Web-based medical database entries were searched. On the premise of existing evidence, we have discussed mechanisms likely contributing to nephroprotection by SGLT2i in patients with non-diabetic CKD. EXPERT OPINION: Further elucidation of mechanisms of nephroprotection offered by SGLT2i is required to extend its use as a nephroprotective agent. The use of non-traditional markers of kidney damage in future studies would improve the evaluation of their role in attenuating CKD progression. Emerging animal data support the early use of SGLT2i in states of modest proteinuria for superior outcomes. Future long-term trials in patients should aim to address the time of intervention with SGLT2i during the natural disease course of CKD for best outcomes.