Cardiorenal protection of SGLT2 inhibitors—Perspectives from metabolic reprogramming

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed as a novel class of anti-hyperglycaemic drugs, have been shown to significantly improve metabolic indicators and protect the kidneys and heart of patients with or without type 2 diabetes mellitus. The possible mechanisms mediating these unexpected cardiorenal benefits are being extensively investigated because they cannot solely be attributed to improvements in glycaemic control. Notably, emerging data indicate that metabolic reprogramming is involved in the progression of cardiorenal metabolic diseases. SGLT2 inhibitors reprogram systemic metabolism to a fasting-like metabolic paradigm, involving the metabolic switch from carbohydrates to other energetic substrates and regulation of the related nutrient-sensing pathways, which might explain some of their cardiorenal protective effects. In this review, we will focus on the current understanding of cardiorenal protection by SGLT2 inhibitors, specifically its relevance to metabolic reprogramming.