This 2021 review article explores the multifaceted role of metformin in modulating autophagy across various biological systems. Metformin primarily induces autophagy through activation of AMP-activated protein kinase (AMPK), leading to inhibition of the mTOR pathway. It also influences other signaling pathways, including AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221. Additionally, metformin can