fisetin + metformin

Fisetin + metformin is an experimental combination therapy consisting of fisetin, a natural flavonoid with senolytic and anti-cancer properties, and metformin, a well-established oral antihyperglycemic agent primarily used for type 2 diabetes. Fisetin acts as a senolytic by selectively inducing apoptosis in senescent cells through modulation of the PI3K-Akt-Bcl-2/Bcl-xl pathway and suppressing the senescence-associated secretory phenotype (SASP). Metformin improves insulin sensitivity mainly via activation of AMP-activated protein kinase (AMPK), leading to enhanced glucose uptake, reduced hepatic gluconeogenesis, increased autophagy, and decreased inflammation. The combination has demonstrated synergistic effects in preclinical models—showing superior anti-aging activity in diabetic vascular aging models compared to monotherapy[2], as well as enhanced cytotoxicity against breast cancer cell lines when co-delivered using mesoporous silica nanoparticles[1][3][5]. This synergy is attributed to complementary mechanisms targeting cellular metabolism, mitochondrial function (mitohormesis), gene expression regulation (e.g., upregulation of tumor suppressor miRNAs), and clearance of dysfunctional cells.

Other names

fisetin and metformin combinationfisetin-metformin