Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs

Abstract

Brain tumors are complex, heterogeneous malignancies, often associated with significant morbidity and mortality. Emerging evidence suggests the important role of metabolic syndrome, such as that observed in diabetes mellitus, in the progression of brain tumors. Several studies indicated that hyperglycemia, insulin resistance, oxidative stress, and altered adipokine profiles influence tumor growth, proliferation, and treatment resistance. Intriguingly, antidiabetic drugs (e.g., metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and thiazolidinediones) have shown promise as adjunctive or repurposed agents in managing brain tumors. Metformin can impair tumor cell proliferation, enhance treatment sensitivity, and modify the tumor microenvironment by activating AMP-activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR) signaling pathways. DPP-4 inhibitors and GLP-1 receptor agonists can target both metabolic and inflammatory aspects of brain tumors, while thiazolidinediones may induce apoptosis in tumor cells and synergize with other therapeutics. Consequently, further studies and clinical trials are needed to confirm the efficacy, safety, and utility of metabolic interventions in treating brain tumors. Here, we review the evidence for the metabolic interconnections between metabolic diseases and brain tumors and multiple actions of anti-diabetes drugs in brain tumors.