Metformin influences progression in diabetic glioblastoma patients

Adeberg, Sebastian; Bernhardt, Denise; Harrabi, Semi; Bostel, Tilman; Mohr, A.; Koelsche, Christian; Diehl, Christian; Rieken, Stefan; Debus, Jürgen

doi:10.1007/s00066-015-0884-5

Cited by 38 publications

(46 citation statements)

References 52 publications

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“…Although patients treated with sulfonylureas had worse outcomes, patients treated with metformin had higher median survival compared with all other anti-diabetic drugs (Welch and Grommes 2013). Two years later, Adeberg et al (2015) investigated the influence of diabetes mellitus, corticosteroid therapy and metformin therapy on progression and survival in primary GBM patients. Among 276 patients with primary GBM, forty patients (14.5 %) were identified with a pretherapeutic history of diabetes, and 20 (50 %) of them were treated with metformin (Adeberg et al 2015).…”

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

“…Two years later, Adeberg et al (2015) investigated the influence of diabetes mellitus, corticosteroid therapy and metformin therapy on progression and survival in primary GBM patients. Among 276 patients with primary GBM, forty patients (14.5 %) were identified with a pretherapeutic history of diabetes, and 20 (50 %) of them were treated with metformin (Adeberg et al 2015). Survival and correlations were assessed via t test and log-rank, univariate and multivariate Cox proportional hazards ratio analyses (Adeberg et al 2015).…”

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

“…Survival and correlations were assessed via t test and log-rank, univariate and multivariate Cox proportional hazards ratio analyses (Adeberg et al 2015). Persistent mild and excessive hyperglycemia was correlated with lower survival rates (Adeberg et al 2015). Corticosteroid usage was associated with lower progression-free and overall survival in the multivariate analysis (Adeberg et al 2015).…”

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

“…Among 276 patients with primary GBM, forty patients (14.5 %) were identified with a pretherapeutic history of diabetes, and 20 (50 %) of them were treated with metformin (Adeberg et al 2015). Survival and correlations were assessed via t test and log-rank, univariate and multivariate Cox proportional hazards ratio analyses (Adeberg et al 2015). Persistent mild and excessive hyperglycemia was correlated with lower survival rates (Adeberg et al 2015).…”

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

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A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Elmacı

Altinöz²

2016

Biochem Genet

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Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a metabolic adjuvant therapy for PC and GBM.

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Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

Section: Metformin Efficacy In Gbm: Clinical Evidencementioning

confidence: 99%

See 2 more Smart Citations

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Elmacı

Altinöz²

2016

Biochem Genet

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“…Importantly, the energetic metabolism can bridge the above reported pathology with both metabolic effects and gut microbial activity. In fact, Adeberg et al reported that metformin is associated with prolonged progression-free survival in diabetic glioblastoma patients [71]. Notably, numerous experimental evidences link the metabolic effects of metformin with gut microbial modulation in both humans, where metformin increased the abundance in Escherichia spp.…”

Section: Brain and Mirsmentioning

confidence: 99%

MicroRNAs: Decoders of Dysbiosis into Metabolic Diseases?

Sérino¹

2016

J Diabetes Metab

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The identification of molecular factors bridging gut microbiota dysbiosis to alterations of host metabolism still remains a major goal in biomedical research. In fact, on one hand, there is a worldwide consensus about the systemic impact, from brain to liver, from heart to adipose tissue, of gut microbiota dysbiosis. On the other hand, beyond the microbial production of short chain fatty acids and their vast metabolic properties, little is known about the molecular mechanisms linking a change in the activity of gut microbes to a modification of host cell metabolism. In this context, microRNAs (also known as miRs) are promising molecules which could allow explaining how dysbiosis is converted into metabolic outcomes since: 1-miRs are pleiotropic regulators of gene expression, targeting multiple mRNAs at once; 2-miRs expression in specific organs such as the intestine has been demonstrated to be under the control of gut microbiota; 3-alterations in miRs expression have been found in the majority of tissues targeted by gut microbiota dysbiosis during metabolic diseases such as liver, adipose tissue, pancreas, skeletal muscle, intestine, heart and also the brain. In this review publications in the growing field of miRsbased metabolic control at a systemic level will be discussed together with a putative link with gut microbiota dysbiosis.

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Use of metformin and survival of patients with high‐grade glioma

Seliger

Luber

Gerken

et al. 2018

Intl Journal of Cancer

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High-grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population-based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox-regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81, HR for PFS = 0.29; 95% CI = 0.11-0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57-1.20) or PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression-free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin.

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Metformin influences progression in diabetic glioblastoma patients

Cited by 38 publications

References 52 publications

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

MicroRNAs: Decoders of Dysbiosis into Metabolic Diseases?

Use of metformin and survival of patients with high‐grade glioma

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