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Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing
Amro H Mohammad1, Sukhdeep Jatana1, Miguel Angel Ruiz-Barerra2,3
1Faculty of Medicine, McGill University, Montreal, Canada.
Purpose:
New treatments are needed to improve the overall survival of patients with glioblastoma Metformin is known for anti-tumorigenic effects in cancers, including breast and pancreas cancers. In this study, we assessed the association between metformin use and overall survival in glioblastoma patients.
Methods:
We retrospectively studied 241 patients who underwent surgery at diagnosis of glioblastoma between 2014 and 2018. Metformin was used for pre-existing type 2 diabetes mellitus or in the prevention or management of glucocorticoid induced hyperglycemia. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios for multivariate analysis.
Results:
Metformin use was associated with longer survival in patients with tumors that had a methylated O6-methylguanine DNA methyltransferase gene (MGMT) promoter (484 days 95% CI: 56-911 vs. 394 days 95% CI: 249-538, Log-Rank test: 6.5, p = 0.01). Cox regression analysis shows that metformin associates with lower risk of death at 2 years in patients with glioblastoma containing a methylated MGMT promoter (aHR = 0.497, 95% CI 0.26-0.93, p = 0.028).
Conclusion:
Our findings suggest a survival benefit with metformin use in patients with glioblastomas having methylation of the MGMT promoter.
Insights
Metformin use may improve survival for glioblastoma patients with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter. This suggests a potential survival benefit in this specific patient subgroup.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- Metformin, a diabetes drug, exhibits anti-tumorigenic properties in various cancers.
- There is a need to explore novel therapeutic strategies for glioblastoma patients.
Purpose of the Study:
- To investigate the association between metformin use and overall survival in glioblastoma patients.
- To determine if metformin confers a survival advantage in glioblastoma.
- To explore the role of MGMT promoter methylation in this association.
Main Methods:
- Retrospective study of 241 glioblastoma patients diagnosed between 2014-2018.
- Metformin use was documented for diabetes or hyperglycemia management.
- Survival analysis utilized Kaplan-Meier curves, log-rank test, and Cox-proportional hazards models.
Main Results:
- Metformin use was linked to longer survival in patients with methylated MGMT promoter (484 days vs. 394 days).
- Cox regression indicated metformin use was associated with a reduced risk of death at 2 years in this subgroup (aHR=0.497).
- The association was statistically significant for patients with methylated MGMT promoter (p=0.01 for survival, p=0.028 for 2-year risk).
Conclusions:
- Metformin use suggests a potential survival benefit for glioblastoma patients with a methylated MGMT promoter.
- This finding highlights the importance of MGMT promoter methylation status in predicting treatment response.
- Further prospective studies are warranted to confirm these results.
