Surreal illustration of a brain with metformin pills on a graph, representing the uncertain relationship between the drug and glioma treatment.

Metformin and Glioma: Unraveling the Controversy

Lena Voss in Health & Wellness December 2025 • 5 min read.

"A critical look at metformin's potential impact on high-grade glioma survival, and why the results might not be as clear-cut as they seem."

The quest for effective cancer treatments is relentless, with researchers constantly exploring new avenues and repurposing existing drugs. One such drug that has garnered attention in the field of oncology is metformin, a widely used medication for managing type 2 diabetes. Recent studies have hinted at its potential benefits in treating various cancers, including high-grade glioma (HGG), an aggressive form of brain tumor. However, the evidence remains contentious, with conflicting results and lingering questions.

A recently published study by Seliger et al. investigated the prognostic effect of metformin on HGG patients, sparking both excitement and debate within the medical community. While the study suggested a possible survival advantage for patients with Grade III glioma, a closer examination reveals several underlying issues that warrant careful consideration. It's crucial to approach these findings with a balanced perspective, acknowledging the potential while remaining aware of the limitations.

This article aims to dissect the complexities surrounding metformin's role in glioma treatment. We'll delve into a critical analysis of the Seliger et al. study, exploring the statistical, biological, and clinical considerations that may influence the interpretation of its results. By unraveling these factors, we hope to provide a clearer understanding of the current state of research and guide cautious decision-making in the management of this challenging disease.

Questionable statistics: Why the numbers might not tell the whole story

Surreal illustration of a brain with metformin pills on a graph, representing the uncertain relationship between the drug and glioma treatment.

The Seliger et al. study analyzed a substantial cohort of 1093 HGG patients, but only a small fraction (5.0%) were receiving metformin. Of those, only 11 patients had Grade III glioma. This raises concerns about statistical power and the potential for skewed results. A significant issue is the apparent lack of case-control or propensity score matching, which could have minimized statistical noise and provided a more accurate assessment of metformin's impact.

Without proper matching, there's a risk of overemphasizing the alternative hypothesis (that metformin improves survival) while downplaying the null hypothesis (that it has no effect). This is especially problematic given the small sample size of the metformin-treated group. It's like trying to draw conclusions from a handful of votes in a large election – the results might not be representative of the entire population.

Selection bias could also be a factor. The study relied on pre-existing population-based and multicenter databases, raising questions about the consistency of data collection and diagnostic criteria.
For instance, IDH testing, a crucial diagnostic tool for glioma, only became standard practice in 2009. This means that a significant proportion of patients prior to that year may not have been tested, potentially affecting the accuracy of the analysis.
The authors note that due to the data generating from pre-existing population-based and multicenter databases, the results are not likely prone to selection bias.This may not be completely accurate, for the prospective nature data was collected from 1998-2013 without clearly defined variables for this study in mind.

The study also included several covariates with a high percentage of missing data ('Unknown' values), such as extent of resection (EOR), isocitrate dehydrogenase (IDH) status, and body mass index (BMI). It's unclear how these missing data points were handled in the regression analyses, but if they were simply categorized as 'Unknown,' it could have diluted the statistical power and further biased the results. Such analytical choices significantly affect the reliability of the conclusions.

The Verdict: Proceed with Caution

While the Seliger et al. study presents an intriguing glimpse into the potential of metformin as a treatment for Grade III glioma, it's crucial to interpret the findings with caution. The statistical limitations, potential for bias, and unanswered biological questions raise significant concerns about the reliability of the results.

Assuming greater congruency between Grades III and IV glioma, it is not clear whether Grade III glioma benefiting from metformin, or Grade IV glioma not benefiting from metformin, is more representative of the natural response of HGG. Ultimately, it should be agreed upon that the findings of this study are best validated by prospective studies.

Until more robust evidence emerges, any adjustments to clinical management with metformin for Grade III glioma, or HGG, based on these results should be considered with extreme caution. Further research, including prospective studies with rigorous controls, is needed to fully elucidate the role of metformin in glioma treatment and determine whether it truly offers a survival advantage for specific patient subgroups.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1002/ijc.31987, Alternate LINK

Title: Connecting The Dots Between Metformin And High‐Grade Glioma

Subject: Cancer Research

Journal: International Journal of Cancer

Publisher: Wiley

Authors: Victor M. Lu

Published: 2019-01-05

Everything You Need To Know

What is the main topic being discussed, and why is it important?

Metformin, a widely used medication for type 2 diabetes, has shown potential in treating high-grade glioma (HGG), an aggressive form of brain tumor. The article discusses a study by Seliger et al. which investigated the impact of Metformin on HGG patients. This is significant because it explores repurposing an existing drug for cancer treatment, offering a potential new avenue for managing this challenging disease. However, the evidence is still contentious.

What are the statistical limitations of the study mentioned in the article?

The Seliger et al. study analyzed 1093 HGG patients, but only a small percentage were receiving Metformin. The article emphasizes the importance of statistical power and the potential for skewed results due to this small sample size, especially for Grade III glioma patients. The study's reliance on pre-existing databases and the lack of case-control or propensity score matching contribute to concerns about the validity of its conclusions. These limitations may impact the accuracy of Metformin's impact on survival outcomes.

What are the data-related issues and inconsistencies that may affect the study's conclusions?

The study used pre-existing population-based and multicenter databases. This method can be prone to inconsistencies in data collection and diagnostic criteria. IDH testing, a crucial diagnostic tool, was not standard before 2009, potentially affecting the accuracy of the analysis. Moreover, missing data points, such as the extent of resection (EOR), isocitrate dehydrogenase (IDH) status, and body mass index (BMI), could dilute statistical power and bias the results. The study notes that the data wasn't collected with the specific variables in mind, possibly influencing the outcome.

How could missing data in the study affect its findings?

The regression analyses may have been affected by missing data, as they could have been categorized as 'Unknown,' potentially diluting the statistical power. The extent of resection (EOR), isocitrate dehydrogenase (IDH) status, and body mass index (BMI) were included as covariates with a high percentage of missing data. The handling of these missing data points significantly affects the reliability of the conclusions.

What is the final verdict on the study's findings, and what does it suggest?

While the Seliger et al. study offers an initial insight into Metformin as a treatment for Grade III glioma, it's essential to approach the findings with caution due to the limitations. The article stresses the importance of understanding the statistical issues and potential biases before drawing definitive conclusions. It encourages a balanced perspective, acknowledging the potential while remaining aware of the limitations, to make informed decisions in managing this challenging disease. Further research is necessary to fully determine the role of Metformin in the treatment of glioma.