Repurposing glucose-lowering drugs for cancer therapy

Abstract The acknowledged relationship between metabolism and cancer retains important potential as a novel target in therapy. Reallocating glucose-lowering drugs (GLDs) in cancer treatment offers valuable perspectives for the ability of these molecules to regulate metabolism at cellular and systemic level. This comprehensive review addresses the therapeutic potential of the main antidiabetic classes of glucose-lowering drugs with emerging anticancer effects, such as metformin, rosiglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium/glucose cotransporter-2 inhibitors. The multifaceted actions of these drugs are explored, from in vitro evidence to clinical evidence as monotherapy or as a sparing agent with chemotherapy and immunotherapy. For each molecule, unconventional mechanisms, benefits, and limitations are dissected and possible concerns addressed, supporting evidence for the potential use of the drug in cancer.