Antineoplastic Effect of Metformin Against Glioblastoma Multiforme In Vitro and In Vivo: A Systematic Review and Meta-Analysis

Background/Objectives: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor associated with poor survival outcomes. Given the significant financial burden of cancer treatments, repurposing existing drugs can reduce costs and enhance therapeutic efficacy. Metformin, an antidiabetic medication, has been investigated for its antineoplastic effects against GBM. Here, we reviewed the in vitro and in vivo effects of metformin through GBM cell viability and overall animal survival, respectively. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction and statistical analyses were performed using Microsoft Excel, and R. Effect sizes were calculated as standard mean differences (SMDs) for in vitro studies assessing cell viability and hazard ratios (HRs) for in vivo mice survival analyses. Results: A total of two-hundred-thirty in vitro studies and five-hundred-sixty-six in vivo studies were screened. Of these, seven in vitro and eight in vivo studies were compatible for the meta-analysis. The random-effects model showed a reduction in cell viability (SMD [95% CI]: 3.70 [2.28, 5.12]). A pooled in vivo survival analysis suggests an increase in overall survival in mice receiving metformin (p-value = 0.055). A random-effects model for overall survival supports this pooled analysis (HR [95% CI]: 0.76 [0.39, 1.46]). Additionally, metformin also showed a reduction in cell viability (SMD [CI]; 2.27 [0.79, 3.75]) and an increase in overall animal survival (HR [CI], 0.23 [0.12, 0.45]) when it was added as an adjuvant to traditional GBM therapies. Conclusions: Our findings from in vitro and in vivo studies support the potential of metformin as an antineoplastic agent against GBM. We plan to extend our analyses into clinical studies to determine if these benefits extend to human patients. Metformin has the potential to revolutionize GBM therapy if a relationship exists due to its inexpensive nature.