metformin + atorvastatin

Metformin + atorvastatin is a combination therapy being investigated for the treatment of prostate cancer, specifically to delay the need for androgen deprivation therapy (ADT) in patients with rising PSA levels after primary treatment. Developed in this context by the University Health Network, Toronto, the regimen combines the metabolic effects of metformin, a biguanide used for type 2 diabetes, with atorvastatin, a statin used for dyslipidemia. Metformin's primary mechanism involves the activation of AMP-activated protein kinase (AMPK) and the inhibition of mitochondrial complex I, which leads to decreased hepatic glucose production and lower circulating insulin levels, potentially inhibiting insulin-mediated tumor growth. Atorvastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, reducing the production of mevalonate and its downstream isoprenoids, which are essential for the post-translational modification of signaling proteins like Ras and Rho that drive cell proliferation. The combination is currently being evaluated in the Phase 2 LIGAND trial.

Brand names

LipitorGlucophage

Other names

Metformin and AtorvastatinLIGAND trial regimen