Abstract: Metformin, a widely used first-line oral hypoglycemic agent for type 2 diabetes mellitus, has gained increasing attention for its potential anticancer properties. Emerging evidence suggests that diabetes and its metabolic environment may influence cancer incidence, progression, and mortality, while glucose-lowering therapies such as metformin may modify these risks. Preclinical and clinical studies indicate that metformin may enhance the efficacy of chemotherapy through mechanisms such as AMP-activated protein kinase activation, inhibition of the mammalian target of the rapamycin pathway, reduction of insulin-mediated proliferative signaling, metabolic reprogramming of tumor cells, and modulation of the tumor microenvironment. Evidence also suggests preferential tumor targeting with limited toxicity to normal tissues, supporting its potential to improve the therapeutic ratio. However, much of the available data remain preclinical or retrospective. Overall, metformin appears to be a promising, safe, and cost-effective adjunct in cancer management, but well-designed prospective clinical trials are necessary to confirm its definitive role in routine oncologic practice. This narrative review involved literature search of electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, to explore the role of metformin as a chemosensitizing agent and normal tissue protectant in cancer therapy.
Gupta et al. (Thu,) studied this question.