Antidiabetic agents as potential cytotoxic candidates for cancer therapy

Abstract Purpose Hyperglycemia is an overlooked triggering factor for cancer, despite being critical to the survival and growth of cancer cells through a unique process known as the “Warburg effect.” Therefore, blocking glycolysis by using antidiabetic agents is an attractive approach for impeding cancer growth and enhancing their responsiveness to cancer treatments, while leaving healthy cells unaffected. This review aims to explore the potential of antidiabetics as cytotoxic agents for cancer treatment through their role as glucose deprivation candidates and the clinical considerations of using antidiabetics with their risk as carcinogenic in cancer therapy. Methods PubMed, Cochrane Library, and Google Scholar were explored by applying the main topic-relevant keywords to consider articles that had been published up to February 2024 and which met our selection criteria. Results The potential of antidiabetic agents to modify the risk of cancer is an exciting area of research in cancer therapy. Some classes of antidiabetics, such as biguanide, sulfonylureas, dipeptidyl peptidase 4 (DPP4) inhibitors, and sodium–glucose co-transporter 2 (SGLT2) inhibitors, have a direct cytotoxic effect on cancer cells, while others, such as glucagon-like peptide 1 (GLP-1) agonists and thiazolidinediones, have an indirect cytotoxic effect on cancer cells. Conclusion Antidiabetic agents differ in their cytotoxic effectiveness toward cancer cells through several mechanisms. Apart from their potential effects on carcinogenicity, these medications hold promise for future cancer treatment. However, not all antidiabetic agents were good candidates for repurposing because of the well-documented carcinogenicity risk.