Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes and Cancer Therapy

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral agents that reduce renal glucose reabsorption, producing glycosuria and improving glycaemic control in type 2 diabetes. Beyond their primary antihyperglycaemic action, these drugs have demonstrated benefits in cardiovascular and renal outcomes, with reductions in heart failure hospitalisations and slowing of chronic kidney disease progression, effects that appear partly independent of blood-glucose lowering. More recently, preclinical and early clinical studies have uncovered potential anticancer activities of SGLT2 inhibitors. These actions range from disruption of tumour cell metabolism—through mitochondrial dysfunction, energy stress and induction of autophagy—to modulation of signalling pathways implicated in proliferation and survival. Evidence also suggests a role for these agents in protecting against chemotherapy-induced cardiotoxicity, thereby linking their cardioprotective and anticancer profiles. Taken together, SGLT2 inhibitors are emerging as multifunctional therapies with global significance for metabolic diseases, cardiorenal protection and, increasingly, adjunctive roles in oncology.

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Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes and Cancer Therapy publication trend

The graph below shows the total number of articles in sodium-glucose cotransporter 2 inhibitors in diabetes and cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Sodium–glucose cotransporter 2 (SGLT2): A membrane protein in renal proximal tubules responsible for reabsorbing filtered glucose.

Glycosuria: The excretion of glucose in urine, a consequence of reduced renal glucose reabsorption.

Autophagy: A regulated cellular process that degrades and recycles damaged organelles and proteins to maintain metabolic homeostasis.

Endoplasmic reticulum-phagy (ER-phagy): A selective form of autophagy targeting portions of the endoplasmic reticulum for lysosomal degradation under stress conditions.

PI3K/AKT signalling pathway: A key intracellular cascade that regulates cell survival, growth and metabolism, often activated by growth factors and hormones.

References

1. SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells. Cellular & Molecular Biology Letters (2024).
2. SGLT-2 Inhibitors in Cancer Treatment—Mechanisms of Action and Emerging New Perspectives. Cancers (2022).
3. Dapagliflozin Mitigates Doxorubicin-Caused Myocardium Damage by Regulating AKT-Mediated Oxidative Stress, Cardiac Remodeling, and Inflammation. International Journal of Molecular Sciences (2022).
4. Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks. Journal of Biological Chemistry (2020).