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Original research
Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer
  1. Cho-Han Chiang1,
  2. Cho-Hung Chiang2,3,
  3. Cho-Hsien Chiang4,5,
  4. Kevin Sheng-Kai Ma6,7,
  5. Chun-Yu Peng8,
  6. Yuan Ping Hsia9,
  7. Chuan-Sheng Horng10,
  8. Cheng-Ying Chen11,
  9. Yu-Cheng Chang12,
  10. Xin Ya See13,
  11. Yuan-Jen Chen14,
  12. Shih-Syuan Wang12,
  13. Giselle A Suero-Abreu15,
  14. LR Peterson16,
  15. Paaladinesh Thavendiranathan17,
  16. Philippe Armand18,
  17. Cheng-Ming Peng12,19,
  18. Her-Shyong Shiah20,21,
  19. Tomas G Neilan15,22
  1. 1Department of Medicine, Mount Auburn Hospital, Cambridge, Massachusetts, USA
  2. 2Department of General Division, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Taipei, Taiwan
  3. 3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  4. 4Department of Medical Education, Kuang Tien General Hospital, Taichung, Taiwan
  5. 5London School of Hygiene & Tropical Medicine, London, UK
  6. 6Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  7. 7Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
  8. 8Department of Medicine, Danbury Hospital, Danbury, Connecticut, USA
  9. 9Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Taipei, Taiwan
  10. 10Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
  11. 11Department of Medical Education, Cathay General Hospital, Taipei, Taiwan
  12. 12Da Vinci Minimally Invasive Surgery Center, Chung Shan Medical University Hospital, Taichung, Taiwan
  13. 13Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York, USA
  14. 14Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  15. 15Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  16. 16Department of Medicine and Radiology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA
  17. 17Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
  18. 18Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  19. 19Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
  20. 20Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
  21. 21Department of Hematology and Oncology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
  22. 22Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Cho-Han Chiang, Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA; b02401124{at}ntu.edu.tw

Abstract

Objectives Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes.

Methods This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i.

Results From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups.

Conclusions The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.

  • Heart failure

Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Footnotes

  • C-HC, C-HC and C-HC are joint first authors.

  • Twitter @dineshpmcc1

  • Contributors Study concept and design—C-MP, H-SS and TGN. Acquisition of data—Cho-HanC, Cho-HungC, Cho-HsienC, C-YP, YPH, C-SH, C-YC, Y-CC, XYS, Y-JC and S-SW. Analysis of data—Cho-HanC, Cho-HungC, Cho-HsienC, KS-KM and GAS-A. Statistical advice—Cho-HanC and KS-KM. Drafting of the manuscript—Cho-HanC, Cho-HungC, Cho-HsienC, LRP, PT, PA and TGN. Critical revision of the manuscript for important intellectual content—Cho-HanC, Cho-HungC, Cho-HsienC, LRP, PT, PA, C-MP, H-SS and TGN. Study supervision—TGN. Guarantor for overall content—Cho-HanC.

  • Funding This work was supported by the National Institutes of Health/National Heart, Lung, Blood Institute (R01HL137562, R01HL130539, K24HL150238 to TGN). TGN holds the Michael and Kathryn Park Chair in Cardiology and was also supported, in part, through a kind gift from A Curtis Greer and Pamela Kohlberg, Christina and Paul Kazilionis and a Hassenfeld Scholar Award. PT is supported by a Canada Research Chair in Cardiooncology.

  • Competing interests TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, BMS, H3-Biomedicine, AbbVie, C4-Therapeutics, Roche, Sanofi and Genentech, outside of the current work. TGN has received grant funding from AstraZeneca and BMS. PA has served as a consultant for Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, Astra Zeneca, Genentech, Xencor, outside of the current work. PA has received research funding from Kite, Merck, BMS, Affimed, Adaptive, Tensha, Otsuka, Sigma Tau, Genentech/Roche, IGM, and speaking honoraria from Merck and BMS, all unrelated to the current work. LRP has stock in Johnson and Johnson, Exact Sciences, Adverum Biotechnology, Crisper Therapeutics, Editas Med., Integra Lifesciences, Medtronic, Seagen Inc., Shockwave Medical, outside of the current work. All other authors have no conflict of interest to disclose.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.