Unveiling the anticancer potential of SGLT-2 inhibitors: mechanisms and prospects in clinical oncology—a narrative review

In recent years, cancer has become more prevalent among younger populations, increasing the burden on public health and the economy. Current cancer treatments are often costly and have long trial periods. Sodium-glucose cotransporter-2 inhibitors (SGLT-2is), including dapagliflozin and canagliflozin, were originally developed for blood glucose control, but have shown promise in anticancer applications. These inhibitors work by inhibiting glucose uptake in tumor cells, thus limiting the energy supply needed for tumor growth. For instance, in lung and hepatocellular cancers, SGLT-2is have been demonstrated to reduce tumor volume and suppress metastasis by modulating key signaling pathways, such as AMPK/mTOR and HIF-1α. Additionally, their ability to enhance the efficacy of chemotherapy and immunotherapy further underscores their potential in cancer treatment. Numerous studies have been conducted on this topic. Diabetes mellitus (DM) is increasingly affecting younger populations and overlaps significantly with cancer. DM patients face higher cancer risks, particularly for liver, colorectal, and pancreatic cancers, with studies indicating up to a 20% increased risk. This highlights the need to consider both conditions in treatment strategies and understand the mechanisms linking DM and cancer to improve outcomes. This study explores the relationship between SGLT-2is and cancer, focusing on their mechanisms in various tumor types and their synergistic effects in combination with other therapies. In the current study, we determined the relationship between SGLT-2is and cancer, and elaborated on the role and mechanisms of SGLT-2is in tumors at different primary sites. In addition, we introduced the anti-tumor effects of SGLT-2is in combination with other means and the underlying mechanisms. From the single-operator to combined-operator level, we reveal the prospects of SGLT-2is in clinical oncology and the future outlook.