19/08/2025
Promising use of metformin in treating neurological disorders, beyond its anti-diabetic effect.
Neural Regen Res. 2023 Sep 22;19(5):1045–
In the last decades, several studies have shown that patients with T2D treated with metformin had a reduction in cancer incidence (Yu et al., 2019). The life expectancy of patients with T2D is typically reduced by up to 10 years (Waugh et al., 1989), while a study reported that diabetic patients treated with metformin monotherapy had longer survival rates than a matched, non-diabetic control (Bannister et al., 2014). The ability of metformin to extend the lifespan and improve the health of T2D patients and animal models has sparked interest in the drug as an anti-aging agent. More recently, metformin has been shown to promote neurogenesis, leading to the improvement of spatial memory formation, cognition, and motor function (Wang et al., 2012; Dadwal et al., 2015). These studies demonstrate that metformin has additional benefits beyond its anti-diabetic effect.
Multiple processes in the central nervous system, including neuroprotection, neural regeneration, angiogenesis, and anti-inflammation, can all be stimulated by metformin, making it an ideal drug candidate to treat neurological degenerative diseases. Metformin acts through multiple signaling pathways including energy sensing (AMP-activated protein kinase (AMPK) signaling), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling, lipid signaling (phospholipids and eicosanoids), inflammatory signaling, and mitochondrial-related signaling to modulate brain function (Rena et al., 2017; Rotermund et al., 2018). This review will highlight recent literature on the role of metformin in mitochondria-related metabolic perturbations and impaired molecular pathways in various neurologic diseases and provide insights into the potential use of biomarker-guided metformin treatment for personalized medicine.