SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, known as Gliflozins, are a class of Glucose‐lowering drugs in adults with type 2 diabetes (T2D) that induce glucosuria by blocking SGLT2 co‐transporters in the proximal tubules. Several lines of evidence suggest that SGLT2 inhibitors regulate multiple mechanisms associated with the regulation of varying cellular pathways. The 5′‐adenosine monophosphate‐activated protein kinase (AMPK) pathway plays an important role in metabolic homeostasis by influencing cellular processes. Recently, it has been shown that SGLT2 inhibitors can affect the AMPK pathway in differing physiological and pathological ways, resulting in kidney, intestinal, cardiovascular, and liver protective effects. Additionally, they have therapeutic effects on nonalcoholic fatty liver disease and diabetes mellitus‐associated complications. In this review, we summarize the results of studies of AMPK‐associated therapeutic effects of SGLT2 inhibitors in different organelle functions. Significance statement: Recent randomized controlled trials (RCTs) have clearly shown the positive assets of SGLT2 inhibitors for renal, heart, intestinal, and hepatic protection. Furthermore, AMPK activation is critical in the regulation of whole‐body energy balance in health and diseases. Besides its classical metabolic regulatory role, increasing evidence suggests that AMPK regulation plays a crucial part in the pathogenesis of disease. In this review, we signify AMPK activation‐mediated therapeutic effects of SGLT2 inhibitors in multiple organs. [ABSTRACT FROM AUTHOR]