Repurposing sodium-glucose co-transporter 2 inhibitors (SGLT2i) for cancer treatment – A Review

Abstract

Developed as an antidiabetic drug, recent evidence suggests that several sodium-glucose co-transporter 2 inhibitors (SGLT2i), especially canagliflozin and dapagliflozin, may exhibit in vitro and in vivo anticancer activities in selected cancer types, including an inhibition of tumor growth and induction of cell death. When used in combination with chemotherapy or radiotherapy, SGLT2i may offer possible synergistic effects in enhancing their treatment efficacy while alleviating associated side effects. Potential mechanisms include a reduction of glucose uptake into cancer cells, systemic glucose restriction, modulation of multiple signaling pathways, and regulation of different gene and protein expression. Furthermore, preliminary clinical findings have reported potential anticancer properties of canagliflozin and dapagliflozin in patients with liver and colon cancers respectively, with reference to decreases in their tumor marker levels. Given its general tolerability and routine use in diabetes management, SGLT2i may be a good candidate for drug repurposing in cancer treatment and as adjunct to conventional therapies. While current evidence reveals that only certain SGLT2i appear to be effective against selected cancer types, further studies are needed to explore the antitumor abilities of each SGLT2i in various cancers. Moreover, clinical trials are called for to evaluate the safety and feasibility of introducing SGLT2i in the treatment regimen of patients with specific cancers, and to identify the preferred route of drug administration for targeted delivery to selected tumor sites.