metformin + ritonavir

This combination therapy, investigated by City of Hope Medical Center, consists of the anti-diabetic agent metformin hydrochloride and the HIV protease inhibitor ritonavir. The regimen was designed to exploit the metabolic vulnerabilities of cancer cells in relapsed/refractory multiple myeloma and chronic lymphocytic leukemia. Ritonavir acts as an inhibitor of the glucose transporter GLUT4, thereby blocking glycolysis, while metformin inhibits mitochondrial complex I to prevent compensatory oxidative phosphorylation. Preclinical evidence suggested this dual inhibition suppresses AKT and mTORC1 signaling and reduces levels of the pro-survival protein MCL-1. However, a pilot Phase 1 clinical trial (NCT02948283) evaluating the safety and feasibility of this combination was terminated due to unacceptable toxicities in the target patient population.

Other names

metformin hydrochloride + ritonavirmetformin and ritonavir