Mechanism of metformin regulation in central nervous system: Progression and future perspectives

Metformin as a first-line drug for type 2 diabetes mellitus(T2DM) treatment is widely studied. Metformin can reduce liver glucose output and improve insulin resistance. Recent evidence from in vivo and in vitro has confirmed that metformin can transport across the blood-brain barrier(BBB) and activate specific neurons and neuroglia to exert neurological actions, however, the specific effect of metformin regulation on CNS is still obscure. In this review, we summarized current evidence from preclinical evidence focusing on the regulatory role of metformin in CNS and found that metformin can exert potential neuroprotective, neurotrophic, and neurogenesis-stimulated actions; besides, metformin also exerts antiinflammatory effect by inhibiting microglial activates and regulating microglial polarization. These findings indicate there might be extensive pharmacological efficacy and therapeutic insights of metformin in neurological diseases' clinical application.