A Type Of Diabetic Drugs Called Glitazones Found To Lower Risk Of Brain Cancers

Cancer News: In a recent study led by the University of Bristol, new research sheds light on the potential of glitazones, a type of anti-diabetic drug, in lowering the risk of primary and secondary brain cancers. The study covered in this Cancer News report, suggests that the long-term use of glitazones among diabetic patients may offer a protective effect against brain tumors. This revelation opens the door to the prospect of repurposing these drugs for preventing brain metastasis in cancer patients, particularly those at a heightened risk of secondary cancers like breast and lung cancer.


A Type Of Diabetic Drugs Called Glitazones Found To Lower Risk Of Brain Cancers

Background and Drug Overview
Glitazones, or PPAR γ agonists, are a class of drugs known for their role in managing diabetes. These drugs, alongside PPAR- α agonists called fibrates, are clinically significant due to their widespread safe use in treating high cholesterol (hyperlipidemia) and diabetes. The safety and cost-effectiveness of these drugs make them promising candidates for repurposing in preventing brain cancers and reducing the risk of secondary tumors by inhibiting tumor growth.
 
PPARs, or peroxisome proliferator-activated receptors, are ligand-activated transcription factors crucial for cellular homeostasis. Within the PPAR family, PPAR- α and PPAR- γ play pivotal roles, and drugs like fibrates and glitazones target these receptors.
 
Glitazones, also called TZDs, are drugs that activate the PPAR-γ (gamma) transcriptional system, thereby promoting the metabolism of glucose. The main drugs are rosiglitazone, the first, but now suspended in Europe, and the safer pioglitazone is now approved in many countries.
 
Previous studies have hinted at the potential of these drugs in preventing brain tumors, with some animal models and early human trials showcasing positive outcomes.
 
The expression of PPARs in brain cells, including tumor stem cells, suggests a potential avenue for these drugs to inhibit angiogenesis and contribute to preventing brain cancers.
 
Research Methodology
The research team utilized primary care records from the UK GP database Clinical Practice Research Datalink (CPRD), which encompasses data from over 2,000 GPs across the UK. Two case-controlled studies were conducted, focusing on primary and secondary brain tumors identified within CPRD between 2000 and 2016. The study included individuals treated with anti-diabetic or anti-hyperlipidemic drugs.
 
Results and Findings
The study identified a total of 7,496 individuals with brain tumors, categorizing them into 4,471 primary and 3,025 secondary cases. In the analysis of glitazones, there were 480 cases with 1,920 controls. Strikingly, long-term use of glitazones by diabetic patients was associated with a reduced risk of both primary and secondary brain tumors compared to patients on other medications. Conversely, no significant association was found between fibrate use for hyperlipidemic patients and any type of brain tumor.
 
Professor Dr Kathreena Kurian, the Head of t he Brain Tumor Research Centre at the University of Bristol, emphasized the potential implications of the findings to various Cancer News outlets. She suggested that glitazones could be involved in a pathway that prevents primary brain tumors and brain metastasis in diabetic and other patients. The study offers a crucial insight into pathways that may prevent the development of primary brain tumors, such as glioma.
 
Professor Dr Yoav Ben-Shlomo, corresponding author and Professor of Clinical Epidemiology at the Bristol Medical School, highlighted the significance of the research. He stated that this study is the largest among diabetic patients, demonstrating a link between long-term glitazone use and decreased primary brain tumor and brain metastasis. He further proposed that if the findings are validated in larger studies and trials, these drugs could potentially be repurposed to prevent brain metastasis in high-risk cancer patients.
 
Discussion and Implications
This pharmacoepidemiological study is the first of its kind to explore the effects of fibrate and glitazone prescription on the risk of brain tumors compared to other treatments for hyperlipidemia and type 2 diabetes. The study delves into the potential protective effects of glitazones on primary and secondary brain tumors, offering a promising avenue for further research.
 
The study builds on previous in vivo research suggesting that fibrate exposure may be protective for brain tumors, particularly gliomas, through modulating PPAR-α inhibition. Similarly, there is evidence supporting the consideration of glitazones as a treatment option from in vivo studies. However, prior to this study, there were no pharmacoepidemiological studies examining whether fibrates or glitazones affect brain tumor risk.
 
In the case–control analysis focusing on glitazones, a modest inverse effect was observed for ever-exposure to glitazones, particularly after exposure durations of four or more years. The findings were consistent for both primary and secondary brain tumors. However, the study acknowledges the need for further research, particularly in exploring potential differences in associations based on the type of primary cancer for subjects with secondary brain tumors.
 
The study found little evidence associating exposure to fibrates with the risk of primary or secondary brain tumors. Sensitivity analyses, investigating potential dose–response effects and exposure status, provided further support for the lack of a significant association between fibrate exposure and brain tumor risk.
 
Strengths and Limitations
The research utilized a nested case - control design within CPRD, a well-established and validated primary care database, minimizing selection bias. Exposure was well-measured, recorded prospectively from medical systems, and cases were included from diagnosis to avoid survivor bias. However, the study acknowledges limitations, such as the potential for confounding by unmeasured factors and the need for larger datasets to replicate the findings.
 
Conclusion and Future Directions
In conclusion, longer exposure to glitazones is inversely associated with the diagnosis of both primary and secondary brain tumors. The study presents a significant step forward in understanding the potential preventive effects of glitazones on brain cancers, opening avenues for further basic science and population-based research.
 
The findings prompt the need for larger studies to replicate and validate these results, ideally with better data on glycemic control and other potential confounders. If the association between glitazones and brain tumors is biologically causal, it could pave the way for a deeper understanding of pathophysiological mechanisms and potential therapies for preventing brain cancers.
 
The researchers suggest that a future double-blind clinical trial could test the hypothesis if stronger evidence emerges from other studies, given the safety and current use of glitazones in managing diabetes. The potential repurposing of glitazones as a preventive strategy against brain metastasis holds promise, offering hope for improved outcomes for cancer patients at high risk of secondary tumors.
 
The study findings were published in the peer reviewed journal: BMJ Open.
https://bmjopen.bmj.com/content/14/2/e072026
 
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