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

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 hypergl...

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Main Authors: Young-Kook Kim, Juhyun Song
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Pharmacological Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1043661825001446
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author Young-Kook Kim
Juhyun Song
author_facet Young-Kook Kim
Juhyun Song
author_sort Young-Kook Kim
collection DOAJ
description 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.
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spelling doaj-art-e00a06f7b3104383b0a952ea5aec543e2025-08-20T03:14:08ZengElsevierPharmacological Research1096-11862025-05-0121510771910.1016/j.phrs.2025.107719Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugsYoung-Kook Kim0Juhyun Song1Department of Biochemistry, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea; Correspondence to: Department of Biochemistry, Chonnam National University Medical School, Hwasun, Jeollanam-do 58128, Republic of Korea.Department of Anatomy, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea; Correspondence to: Department of Anatomy, Chonnam National University Medical School, Hwasun, Jeollanam-do 58128, Republic of Korea.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.http://www.sciencedirect.com/science/article/pii/S1043661825001446Brain tumorMetabolic syndromeAntidiabetic drugsDiabetesObesity
spellingShingle Young-Kook Kim
Juhyun Song
Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
Pharmacological Research
Brain tumor
Metabolic syndrome
Antidiabetic drugs
Diabetes
Obesity
title Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
title_full Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
title_fullStr Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
title_full_unstemmed Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
title_short Metabolic imbalance and brain tumors: The interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
title_sort metabolic imbalance and brain tumors the interlinking metabolic pathways and therapeutic actions of antidiabetic drugs
topic Brain tumor
Metabolic syndrome
Antidiabetic drugs
Diabetes
Obesity
url http://www.sciencedirect.com/science/article/pii/S1043661825001446
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