The effect of metformin on promoting degradation of HIF-1α can also inhibit the allosteric activator of phosphofructokinase-1 6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3), downregulating the expression of PFK1 mediated by PFKFB3 to inhibit glycolysis and cancer cell proliferation (88). Here, HIF1A is linked to cancer.