OBJECTIVES:Recent studies suggest that the use of metformin may lead to more prolonged survival in some, but not all, cancers. Small scale in-vitro studies indicate that metformin use may improve outcomes for Glioblastoma Multiforme (GBM) patients. This systematic literature review and meta-analysis aims to evaluate the association between the use of metformin and survival among GBM patients.

METHODS: A comprehensive electronic search was conducted on PubMed, EMBASE, and Cochrane to retrieve relevant articles from inception to 1 August 2020. The primary endpoints of interest were overall survival (OS) and progression-free survival (PFS). Two independent researchers completed all screening and data extraction processes. Pooled treatment effects were estimated using the DerSimonian and Laird random-effects model approach. Study quality was assessed using the Newcastle-Ottawa Scale (NOS).

RESULTS:The literature search yield 306 articles, from which eight observational cohort studies were identified for the analysis. The eight studies had a total sample size of 3200. The majority of the studies were conducted in Germany, with two from the US and one from Scotland. Four studies that reported a quantitative association between metformin use and overall survival were included in the metanalysis. They provided a non-statistically significant pooled hazard ratio of 0.90 (95% Confidence Interval (CI): 0.68-1.18). Similarly, the pooled association between metformin use and progression-free survival was not statistically significant (HR 0.91 (95 % CI: 0.73-1.15). Each of the studies scored between five and seven on the Newcastle-Ottawa Scale, suggesting moderate design quality.

CONCLUSIONS:Although pooled point estimates suggest favorable survival outcomes for GBM patients using metformin, the associations were not statistically significant. Larger and more robust clinical studies are needed better to understand the effects of metformin across clinical subpopulations of the GBM patients.