Title : A systematic review and meta-analysis on the effect of metformin on glioblastoma multiforme
Abstract:
Glioblastoma multiforme (GBM) is a highly aggressive disease with a poor prognosis for most of the patients. The costs of care can overwhelm these patients at times where work is difficult, so there is a need to evaluate affordable alternatives. There exists a body of literature that has shown that metformin has the potential to act as an anti-neoplastic agent. Here we examined the effects of metformin on GBM in humans, in vivo (experimental animals), and in vitro.
Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed to do the review. We calculate the effect size on median overall survival in humans, the hazard ration (HR) on murine overall survival, and the standard mean difference (SMD) for in vitro cell viability. In humans, rodents, and in vitro, totals of 469, 566, and 230 studies were screened respectively. Of these studies, 4,7,8 studies respectively were compatible for the meta-analysis. In humans, data analysis demonstrated an increase in median overall survival for GBM patients up to 18 months compared to controls (p = 0.00197). Pooled data analysis in mouse model suggests an increase in overall survival in mice receiving metformin (p = 0.055). Random-effects model on these same studies also supports this finding (HR [95% CI]: 0.76 [0.39,1.46]). Random-effects model in vitro demonstrated an increase in cell viability upon treatment with metformin (SMD [95% CI]: 3.70 [2.28, 5.12]).
Overall, our findings support the efficacy of metformin as an anti-neoplastic agent. We anticipate further analyses to find dose-dependent relationships between metformin and the targeted survival outcomes. We will also explore the role of metformin when combined with current therapies such as Temozolomide. We envision metformin to have the potential to become an inexpensive adjuvant to GBM cancer therapy.
