Sodium-Glucose Cotransporter 2 Inhibitors Work as a Regulator of Autophagic Activity in Overnutrition Diseases

Several large clinical trials have shown renal and cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetes patients, and the protective mechanisms need to be elucidated. There have been accumulating studies which report that SGLT2 inhibitors ameliorate autophagy deficiency of multiple organs. In overnutrition diseases, SGLT2 inhibitors affect the autophagy via various signaling pathways, including mammalian target of rapamycin (mTOR), sirtuin 1 (SIRT1), and hypoxia-inducible factor (HIF) pathways. Recently, it turned out that not only stagnation but also overactivation of autophagy causes cellular damages, indicating that therapeutic interventions which simply enhance or stagnate autophagy activity might be a double-edged sword in some situations. A small number of studies suggest that SGLT2 inhibitors not only activate but also suppress the autophagy flux depending on the situation, indicating that SGLT2 inhibitors can regulate autophagic activity and help achieve the appropriate autophagy flux in each organ. Considering the complicated control and bilateral characteristics of autophagy, the potential of SGLT2 inhibitors as the regulator of autophagic activity would be beneficial in the treatment of autophagy deficiency.

Automated summary

SGLT2 inhibitors have been shown to have renal and cardioprotective effects in diabetic patients, potentially by affecting autophagy in multiple organs. However, therapeutic interventions involving these inhibitors may need to carefully consider their dual effects on autophagy.