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The Efficacy and Safety of Sodium Glucose Cotransporter 2 Inhibitors for Patients with Anticancer Therapy: A Meta-Analysis of Cohort Studies Cover

The Efficacy and Safety of Sodium Glucose Cotransporter 2 Inhibitors for Patients with Anticancer Therapy: A Meta-Analysis of Cohort Studies

By: Gang Fan,  Hong Zuo,  Lin Lin,  Chao Xu and  Rui Yan  
Open Access
|Jun 2025

References

  1. 1Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin. Jan 2021;71(1):733. DOI: 10.3322/caac.21654
  2. 2Rodriguez GM, DePuy D, Aljehani M, et al. Trends in epidemiology of esophageal cancer in the US, 1975–2018. JAMA Netw Open. Aug 1 2023;6(8):e2329497. DOI: 10.1001/jamanetworkopen.2023.29497
  3. 3Kwok C, Nolan M. Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications. Front Cardiovasc Med. 2023;10:1150569. DOI: 10.3389/fcvm.2023.1150569
  4. 4Ehrhardt MJ, Leerink JM, Mulder RL, et al. Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. Mar 2023;24(3):e108e120. DOI: 10.1016/S1470-2045(23)00012-8
  5. 5Lenneman CG, Sawyer DB. Cardio-oncology: an update on cardiotoxicity of cancer-related treatment. Circ Res. Mar 18 2016;118(6):100820. DOI: 10.1161/CIRCRESAHA.115.303633
  6. 6Frey MK, Arfsten H, Pavo N, et al. Sacubitril/valsartan is well tolerated in patients with longstanding heart failure and history of cancer and improves ventricular function: real-world data. Cardiooncology. Oct 13 2021;7(1):35. DOI: 10.1186/s40959-021-00121-y
  7. 7He D, Hu J, Li Y, et al. Preventive use of beta-blockers for anthracycline-induced cardiotoxicity: a network meta-analysis. Front Cardiovasc Med. 2022;9:968534. DOI: 10.3389/fcvm.2022.968534
  8. 8de Baat EC, Mulder RL, Armenian S, et al. Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines. Cochrane Database Syst Rev. Sep 27 2022;9(9):CD014638. DOI: 10.1002/14651858.CD014638.pub2
  9. 9Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. Feb 2017;24(1):7379. DOI: 10.1097/MED.0000000000000311
  10. 10McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. Nov 21 2019;381(21):19952008. DOI: 10.1056/NEJMoa1911303
  11. 11Fan G, Guo DL, Zuo H. The impact of sodium-glucose cotransporter-2 inhibitors on lipid profile: a meta-analysis of 28 randomized controlled trials. Eur J Pharmacol. Nov 15 2023;959:176087. DOI: 10.1016/j.ejphar.2023.176087
  12. 12Fan G, Guo DL. The effect of sodium-glucose cotransporter-2 inhibitors on cardiac structure remodeling and function: a meta-analysis of randomized controlled trials. Eur J Intern Med. Aug 2023;114:4957. DOI: 10.1016/j.ejim.2023.04.002
  13. 13Avula V, Sharma G, Kosiborod MN, et al. SGLT2 inhibitor use and risk of clinical events in patients with cancer therapy-related cardiac dysfunction. JACC Heart Fail. Jan 2024;12(1):6778. DOI: 10.1016/j.jchf.2023.08.026
  14. 14Perelman MG, Brzezinski RY, Waissengrin B, et al. Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors. Cardiooncology. Jan 11 2024;10(1):2. DOI: 10.1186/s40959-023-00199-6
  15. 15Arya S, Kaji AH, Boermeester MA. PRISMA reporting guidelines for meta-analyses and systematic reviews. JAMA Surg. Aug 1 2021;156(8):789790. DOI: 10.1001/jamasurg.2021.0546
  16. 16Moskalewicz A, Oremus M. No clear choice between Newcastle-Ottawa Scale and Appraisal Tool for Cross-Sectional Studies to assess methodological quality in cross-sectional studies of health-related quality of life and breast cancer. J Clin Epidemiol. Apr 2020;120:94103. DOI: 10.1016/j.jclinepi.2019.12.013
  17. 17Gongora CA, Drobni ZD, Quinaglia Araujo Costa Silva T, et al. Sodium-glucose co-transporter-2 inhibitors and cardiac outcomes among patients treated with anthracyclines. JACC Heart Fail. Aug 2022;10(8):559567. DOI: 10.1016/j.jchf.2022.03.006
  18. 18Fath AR, Aglan M, Aglan A, et al. Cardioprotective potential of sodium-glucose cotransporter-2 inhibitors in patients with cancer treated with anthracyclines: an observational study. Am J Cardiol. Jul 1 2024;222:175182. DOI: 10.1016/j.amjcard.2024.04.032
  19. 19Abdel-Qadir H, Carrasco R, Austin PC, et al. The association of sodium-glucose cotransporter 2 inhibitors with cardiovascular outcomes in anthracycline-treated patients with cancer. JACC CardioOncol. Jun 2023;5(3):318328. DOI: 10.1016/j.jaccao.2023.03.011
  20. 20Chiang CH, Chiang CH, Chiang CH, et al. Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer. Heart. Feb 23 2023;109(6):470477. DOI: 10.1136/heartjnl-2022-321545
  21. 21Hwang HJ, Kim M, Jun JE, et al. Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes in patients with type 2 diabetes mellitus undergoing anthracycline-containing chemotherapy: an emulated target trial using nationwide cohort data in South Korea. Sci Rep. Dec 8 2023;13(1):21756. DOI: 10.1038/s41598-023-48678-1
  22. 22Huang YM, Chen WM, Jao AT, et al. Effects of SGLT2 inhibitors on clinical cancer survival in patients with type 2 diabetes. Diabetes Metab. Jan 2024;50(1):101500. DOI: 10.1016/j.diabet.2023.101500
  23. 23Luo J, Hendryx M, Dong Y. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival. Br J Cancer. Apr 2023;128(8):15411547. DOI: 10.1038/s41416-023-02177-2
  24. 24Hendryx M, Dong Y, Ndeke JM, et al. Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis. PLoS One. 2022;17(9):e0274519. DOI: 10.1371/journal.pone.0274519
  25. 25Group ESCSD. (2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)). G Ital Cardiol (Rome). Feb 2023;24(2 Suppl 1):e1e130. Linee guida ESC 2022 sulla cardio-oncologia in collaborazione con European Hematology Association (EHA), European Society of Therapeutic Radiology and Oncology (ESTRO) e International Cardio-Oncology Society (IC-OS)elaborate dalla task force sulla cardio-oncologia della Societa Europea di Cardiologia (ESC). DOI: 10.1093/ehjci/jead080
  26. 26Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. Jun 2 2015;131(22):19818. DOI: 10.1161/CIRCULATIONAHA.114.013777
  27. 27Dempke WCM, Zielinski R, Winkler C, et al. Anthracycline-induced cardiotoxicity – are we about to clear this hurdle? Eur J Cancer. May 2023;185:94104. DOI: 10.1016/j.ejca.2023.02.019
  28. 28Fidler MM, Reulen RC, Henson K, et al. Population-based long-term cardiac-specific mortality among 34,489 five-year survivors of childhood cancer in Great Britain. Circulation. Mar 7 2017;135(10):951963. DOI: 10.1161/CIRCULATIONAHA.116.024811
  29. 29Kremer LC, van der Pal HJ, Offringa M, et al. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol. Jun 2002;13(6):81929. DOI: 10.1093/annonc/mdf167
  30. 30Tamargo J, Caballero R, Delpon E. Cancer chemotherapy-induced sinus bradycardia: a narrative review of a forgotten adverse effect of cardiotoxicity. Drug Saf. Feb 2022;45(2):101126. DOI: 10.1007/s40264-021-01132-5
  31. 31Cheng WL, Kao YH, Chen SA, et al. Pathophysiology of cancer therapy-provoked atrial fibrillation. Int J Cardiol. Sep 15 2016;219:18694. DOI: 10.1016/j.ijcard.2016.06.009
  32. 32Rhea I, Burgos PH, Fradley MG. Arrhythmogenic anticancer drugs in cardio-oncology. Cardiol Clin. Nov 2019;37(4):459468. DOI: 10.1016/j.ccl.2019.07.011
  33. 33Roboz GJ, Ritchie EK, Carlin RF, et al. Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide. J Clin Oncol. Nov 20 2014;32(33):37238. DOI: 10.1200/JCO.2013.51.2913
  34. 34Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. Sep 2014;27(9):91139. DOI: 10.1016/j.echo.2014.07.012
  35. 35Herrmann J, Lerman A, Sandhu NP, et al. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. Sep 2014;89(9):1287306. DOI: 10.1016/j.mayocp.2014.05.013
  36. 36Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, Jr., et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol. May 22 2018;71(20):22812290. DOI: 10.1016/j.jacc.2018.02.049
  37. 37Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. Nov 2012;18(11):163942. DOI: 10.1038/nm.2919
  38. 38Chang WT, Lin YW, Ho CH, et al. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients. Arch Toxicol. Feb 2021;95(2):659671. DOI: 10.1007/s00204-020-02951-8
  39. 39Quagliariello V, De Laurentiis M, Rea D, et al. The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin. Cardiovasc Diabetol. Jul 23 2021;20(1):150. DOI: 10.1186/s12933-021-01346-y
  40. 40Kuo HH, Wang KT, Chen HH, et al. Cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus and cancer: a systematic review and meta-analysis. Diabetol Metab Syndr. May 22 2024;16(1):108. DOI: 10.1186/s13098-024-01354-4
  41. 41Mohsin S, Hasan M, Sheikh ZM, et al. Efficacy of SGLT2 inhibitors for anthracycline-induced cardiotoxicity: a meta-analysis in cancer patients. Future Cardiol. Jul 4 2024;113. DOI: 10.1080/14796678.2024.2363673
  42. 42Li HL, Lip GYH, Feng Q, et al. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis. Cardiovasc Diabetol. May 7 2021;20(1):100. DOI: 10.1186/s12933-021-01293-8
  43. 43Fernandes GC, Fernandes A, Cardoso R, et al. Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: a meta-analysis of 34 randomized controlled trials. Heart Rhythm. Jul 2021;18(7):10981105. DOI: 10.1016/j.hrthm.2021.03.028
  44. 44Essa H, Wright DJ, Dobson R, et al. Chemotherapy-induced arrhythmia – underrecognized and undertreated. Am J Med. Oct 2021;134(10):12241231 e1. DOI: 10.1016/j.amjmed.2021.05.026
  45. 45Lega IC, Bronskill SE, Campitelli MA, et al. Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: a population-based study of older women and men with diabetes. Diabetes Obes Metab. Nov 2019;21(11):23942404. DOI: 10.1111/dom.13820
  46. 46Dave CV, Schneeweiss S, Kim D, et al. Sodium-glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: a population-based cohort study. Ann Intern Med. Aug 20 2019;171(4):248256. DOI: 10.7326/M18-3136
  47. 47Wu MZ, Chandramouli C, Wong PF, et al. Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors. Diabetes Metab. Nov 2022;48(6):101367. DOI: 10.1016/j.diabet.2022.101367
  48. 48Cai W, Chong K, Huang Y, et al. Empagliflozin improves mitochondrial dysfunction in diabetic cardiomyopathy by modulating ketone body metabolism and oxidative stress. Redox Biol. Feb 2024;69:103010. DOI: 10.1016/j.redox.2023.103010
  49. 49Dabravolski SA, Zhuravlev AD, Kartuesov AG, et al. Mitochondria-mediated cardiovascular benefits of sodium-glucose co-transporter 2 inhibitors. Int J Mol Sci. May 11 2022;23(10). DOI: 10.3390/ijms23105371
  50. 50Choi J, Matoba N, Setoyama D, et al. The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice. Commun Biol. Mar 17 2023;6(1):278. DOI: 10.1038/s42003-023-04663-y
  51. 51Chase D, Eykyn TR, Shattock MJ, et al. Empagliflozin improves cardiac energetics during ischaemia/reperfusion by directly increasing cardiac ketone utilization. Cardiovasc Res. Dec 19 2023;119(16):26722680. DOI: 10.1093/cvr/cvad157
  52. 52Naeimzadeh Y, Tajbakhsh A, Nemati M, et al. Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies. Eur J Pharmacol. Sep 5 2024;978:176803. DOI: 10.1016/j.ejphar.2024.176803
  53. 53Papadopoli D, Uchenunu O, Palia R, et al. Perturbations of cancer cell metabolism by the antidiabetic drug canagliflozin. Neoplasia. Apr 2021;23(4):391399. DOI: 10.1016/j.neo.2021.02.003
  54. 54Malyszko J, Kozlowska K, Kozlowski L, Malyszko J. Nephrotoxicity of anticancer treatment. Nephrol Dial Transplant. 2017;32:92436.
  55. 55Fadini GP, Sarangdhar M, De Ponti F, Avogaro A, Raschi E. Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors. BMJ Open Diabetes Res Care. 2019;7:e000725. DOI: 10.1136/bmjdrc-2019-000725
DOI: https://doi.org/10.5334/gh.1440 | Journal eISSN: 2211-8179
Language: English
Submitted on: Nov 27, 2024
Accepted on: Jun 4, 2025
Published on: Jun 16, 2025
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2025 Gang Fan, Hong Zuo, Lin Lin, Chao Xu, Rui Yan, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.