Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications

Gastrointestinal diseases have become a global health concern with high incidence and prevalence. Considering that a great many patients with gastrointestinal cancers still suffer from tumor recurrence or distant metastasis even after surgical intervention or neoadjuvant chemotherapy, it is urgently needed to identify new therapeutic drugs. Metformin, originally derived from natural herbs, has been found to be beneficial for many diseases, including not only type 2 diabetes mellitus, cardiovascular disease, liver and kidney disease, and age-related diseases but also different types of cancers. Herein, we comprehensively review the roles and the underlying mechanisms of metformin in gastrointestinal cancers including colorectal, esophageal, and gastric cancers and also inflammatory bowel disease. By integrating the latest research findings, we systematically elaborate on how metformin exerts therapeutic effects on gastrointestinal diseases through the AMPK/mTOR pathway and the effects of combination therapies. This review may offer novel insights for developing therapeutic strategies against gastrointestinal malignancies and related diseases.