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Metformin in High-Grade Glioma: A Systematic Review and Meta-Analysis

Friday, May 3, 2024

    Presenting Author(s)

  • Marcio Yuri Ferreira, MD

    Research Collaborator
    Program in Global Surgery and Social Change - Harvard Medical School. Postgraduate Program in Translational Surgery of Federal University of São Paulo, Brazil

    • Co-Author(s)

  • LC

    Luciano Coelho, MD

    MD
    University Hospital HUUFMA, Brazil, United States

  • LM

    Lucas Mitre, n/a

    Medical Student
    Santa Casa de Sao Paulo School of Medical Sciences
    S?o Paulo, Sao Paulo, Brazil

  • DM

    Daniel Moreno, n/a

    Doctor
    Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., United States

  • JO

    Jéssica Oliveira, n/a

    MS
    National University of Rosario, Argentina, United States

  • AP

    Allan Polverini, n/a

    Medical Doctor
    Hospital de Amor de Barretos - Fundação Pio XII, United States

  • Eloisa Assis

    Medical Student
    Baltic Federal University, Russian Federation

Introduction: High-grade gliomas (HGG) are aggressive tumors known for their poor prognosis. Despite research into its molecular and clinical aspects, current management minimally impacts survival. It is unclear whether combining temozolomide (TMZ) with metformin (MET) enhances survival in this population. The objective was to evaluate overall survival (OS) in patients with HGG treated with TMZ+MET versus TMZ alone.

Methods: We systematically searched Pubmed, Embase, and Cochrane Library databases for studies comparing TMZ+MET vs. TMZ alone for HGG and reporting OS. Heterogeneity was examined with I2 statistics. Statistical analysis was performed using Review Manager 5.4.1. Outcomes were pooled with a random-effects model.

Results: We included 10 studies in the systematic review comparing TMZ + MET (n =346; 9.5%) vs. TMZ (n= 3277; 90.5%) alone for the treatment of adult HGG. OS was reported for all studies; however, the meta-analysis could only pool the data for 5 studies due to absence of standard deviation results from other studies. Average follow-up ranged from 18 months to 88 months. Among the 10 studies, OS was significantly improved with the combination of TMZ + MET in 8 studies. Patients with TMZ+MET had significantly better OS rates as compared with patients on TMZ alone (HR 0.74; 95% CI 0.59-0.93; p=0 < 0.01). There was no significant difference between groups in the outcome of progression-free survival (HR 0.87; 95% CI 0.68-1.12; p=0.29).

Conclusion : The findings of this systematic review and meta-analysis support the use of TMZ+MET in patients with HGG, due to improved OS survival relative to TMZ alone.