High expression levels of genes downregulated by metformin in macrophages, such as TGFBI, IL1B, CD74 and TIMP1, correlated with poor overall survival in glioma patients, as did low expression of the upregulated gene MTHFD2 (Fig. 3E and Fig. S2E), thus suggesting that the beneficial effects on the prognosis of metformin-treated glioma patients may be related to its action on macrophages. This evidence concerns the gene MTHFD2 and glioma.