OBJECTIVE: High-grade gliomas (HGGs) 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) could enhance survival in this population. METHODS: A systematic search on PubMed, Embase, and Cochrane Library databases was conducted for studies comparing TMZ+MET versus TMZ alone for HGG. The outcomes of interest were overall survival, progression-free survival, and subgroup analysis with O6-methylguanine-DNA methyltransferase and patients with diabetes. The analysis comprised outcomes reported as hazard ratios (HRs) and odds ratios with corresponding 95% confidence intervals (CIs) as all the outcomes are continuous. A significance level of P <
0.05 was considered statistically significant. Heterogeneity was assessed using the I RESULTS: Ten studies were included, comprising 3623 patients, of which 346 (9.5%) were assigned for TMZ+MET. The TMZ+MET group was associated with a significant reduction in mortality rates when compared to the TMZ alone group (HR 0.74
95% CI 0.59, 0.93
P <
0.01
I CONCLUSIONS: Our results showed that patients who received TMZ+MET had a significantly higher overall survival than patients who received TMZ alone. These findings support the use of MET along with TMZ for the treatment of HGGs.