The combination of the protease inhibitor ritonavir with metformin has shown antitumor activity in MM both in vitro and in vivo with xenograft mouse models, through inhibition of glucose transporter 4 (GLUT4) and mitochondrial oxidative metabolism, leading to suppression of signaling through the protein kinase B (AKT)/mammalian target of rapamycin complex 1 (mTORC1) pathway known to regulate MCL-1 [124]. This evidence concerns the gene AKT1 and Miyoshi myopathy.