Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule-glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naive diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naive diabetic patients.
