Exploring the Potential of SGLT-2 Inhibitors in Cancer Treatment: Mechanisms, Preclinical Findings, and Clinical Implications
DOI:
https://doi.org/10.12775/QS.2025.37.57224Keywords
SGLT-2 inhibitors, type 2 diabetes, cardiovascular protection, renal outcomes, athletic performance, cancer therapy, sports medicineAbstract
Introduction
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, originally developed for the treatment of type 2 diabetes, have recently attracted attention for their potential applications in oncology. Their potential to modulate tumor metabolism and enhance responses to cancer therapies is an area of increasing interest.
Aim of the study
This review aims to explore the emerging role of SGLT-2 inhibitors in cancer treatment, focusing on their mechanisms of action, preclinical findings, and early clinical evidence. By understanding the potential of these agents to alter tumor metabolism and the immune microenvironment, we can evaluate their therapeutic value in cancer management.
Material and Methods
Data were gathered from peer-reviewed articles, clinical trials, and ongoing research on the use of SGLT-2 inhibitors in combination with chemotherapy, immunotherapy, and other cancer treatments.
Description of the state of knowledge
Preclinical studies suggest that SGLT-2 inhibitors can alter cancer cell metabolism by limiting glucose availability, potentially impeding tumor growth. These agents have demonstrated promise in models of breast, prostate, and pancreatic cancers, reducing cell proliferation and enhancing the efficacy of standard cancer treatments.
Conclusions
SGLT-2 inhibitors represent a novel therapeutic strategy in oncology, with potential to improve outcomes in combination with traditional therapies. However, more extensive clinical trials are required to validate their effectiveness, optimize treatment regimens, and better understand their safety profiles in cancer patients.
References
1. Wiviott SD, et al. Empagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2020;383(22):2117-2128.
2. McMurray JJV, et al. Dapagliflozin and heart failure with reduced ejection fraction. N Engl J Med. 2020;383(15):1413-1424.
3. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
4. Stine ZE, et al. Targeting cancer metabolism with SGLT2 inhibitors. Cancer Cell. 2021;39(5):662-677.
5. Jang JH, et al. Combining SGLT2 inhibitors with immunotherapy: Emerging evidence and future perspectives. J Immunother Cancer. 2023;11(4):e008141.
6. Zinman B, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
7. Rabasa-Lhoret R, et al. Managing diabetes in athletes. Diabetes Spectr. 2017;30(2):101-111.
8. Bonner C, et al. Cellular mechanisms of SGLT-2 inhibitors. Diabetologia. 2015;58(5):1028-1036.
9. Neal B, et al. Canagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.
10. McMurray JJV, et al. Dapagliflozin in heart failure with reduced ejection fraction. J Am Coll Cardiol. 2020;75(2):130-140.
11. Heerspink HJL, et al. SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease: A systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845-855.
12. Zhang Y, et al. SGLT2 inhibitors and tumor metabolism in cancer therapy. Cancer Res. 2022;82(11):2199-2210.
13. Stine ZE, et al. Targeting cancer metabolism with SGLT2 inhibitors. Cancer Cell. 2021;39(5):662-677.
14. Jang JH, et al. Combining SGLT2 inhibitors with immunotherapy: Emerging evidence and future perspectives. J Immunother Cancer. 2023;11(4):e008141.
15. Lee H, et al. SGLT2 inhibitors in cancer treatment: A new approach. J Clin Oncol. 2023;41(6):345-357.
16. Rebours V, et al. Metabolic shifts and implications of SGLT2 inhibitors in cancer treatment. Oncogene. 2022;41(22):3025-3035.
17. Bays HE. Obesity and weight reduction: effects of SGLT-2 inhibitors. Postgrad Med. 2016;128(8):746-759.
18. Burke LM, et al. Hydration strategies in athletes. Sports Med. 2017;47(Suppl 1):47-58.
19. Madsen K, et al. Cardiovascular protection by SGLT2 inhibitors: Mechanisms beyond glucose control. Cardiovasc Diabetol. 2020;19(1):65.
20. Brown E, et al. Renal protection by SGLT2 inhibitors in patients with diabetic nephropathy. Lancet Diabetes Endocrinol. 2020;8(1):21-30.
21. Dutka M, Bobiński R, Francuz T, et al. SGLT-2 Inhibitors in Cancer Treatment-Mechanisms of Action and Emerging New Perspectives. Cancers (Basel). 2022;14(23):5811. Published 2022 Nov 25. doi:10.3390/cancers14235811
22. Laeeq T, Ahmed M, Sattar H, Zeeshan MH, Ali MB. Role of SGLT2 Inhibitors, DPP-4 Inhibitors, and Metformin in Pancreatic Cancer Prevention. Cancers (Basel). 2024;16(7):1325. Published 2024 Mar 28. doi:10.3390/cancers16071325
23. Du D, Liu C, Qin M, et al. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. Acta Pharm Sin B. 2022;12(2):558-580. doi:10.1016/j.apsb.2021.09.019
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Aldona Sokołowska, Klaudia Fikas, Kamil Chwaliszewski, Sebastian Samuła, Michał Mazur, Dorota Waz, Jakub Szarłowicz, Zofia Goliszek, Karolina Łucja Sobek, Wiktoria Tabin-Barczak
![Creative Commons License](http://i.creativecommons.org/l/by-nc-sa/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 101
Number of citations: 0