The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data
We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio = 0.56, 95% confidence interval [CI] = 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (n<sub>SGLT2i</sub> = 24,155; n<sub>DPP4i</sub> = 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio = 0.77, 95% CI = 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n<sub>4C</sub> = 57,779; n<sub>UK_Biobank</sub> = 165,430), we found little evidence to support the association of HbA<sub>1c</sub> with prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.
Authors
- Celine Sze Ling Chui (ORCID: https://orcid.org/0000-0003-1513-8726)
- Jinqiu Yuan (ORCID: https://orcid.org/0000-0003-0016-776X)
- James Yarmolinsky (ORCID: https://orcid.org/0000-0003-4371-0873)
- Jieli Lu (ORCID: https://orcid.org/0000-0003-1317-0896)
- George Davey Smith (ORCID: https://orcid.org/0000-0002-1407-8314)
- Yufang Bi (ORCID: https://orcid.org/0000-0002-9536-2682)
- Jamie Robinson (ORCID: https://orcid.org/0000-0001-8721-6514)
- Olympia Dimopoulou (ORCID: https://orcid.org/0000-0003-3788-245X)
- Youqiong Ye (ORCID: https://orcid.org/0000-0001-8332-4710)
- Zhongshang Yuan (ORCID: https://orcid.org/0000-0002-3527-4488)
- Tom R. Gaunt (ORCID: https://orcid.org/0000-0003-0924-3247)
- Padraig Dixon (ORCID: https://orcid.org/0000-0001-5285-409X)
- Sean Harrison (ORCID: https://orcid.org/0000-0002-7966-0700)
- Yu Xu (ORCID: https://orcid.org/0000-0003-1045-8309)
- Shiu Lun Au Yeung (ORCID: https://orcid.org/0000-0001-6136-1836)
- Bin Cui (ORCID: https://orcid.org/0000-0002-7293-5740)
- Zhiyun Zhao (ORCID: https://orcid.org/0000-0001-5950-2732)
- Zhihe Chen (ORCID: https://orcid.org/0000-0001-8294-6729)
- Sarah Jayne Lewis (ORCID: https://orcid.org/0000-0002-4791-9845)
- Philip Haycock (ORCID: https://orcid.org/0000-0001-5001-3350)
- Ruizhi Zheng (ORCID: https://orcid.org/0000-0002-2068-7597)
- Richard Michael Martin (ORCID: https://orcid.org/0000-0002-7992-7719)
- Tiange Wang (ORCID: https://orcid.org/0000-0003-0723-489X)
- Guang Ning (ORCID: https://orcid.org/0000-0002-5754-7635)
- Lanhui Huang (ORCID: https://orcid.org/0000-0002-1030-9760)
- Chunyan Hu (ORCID: https://orcid.org/0000-0002-8673-3859)
- Qian Yang (ORCID: https://orcid.org/0000-0001-8778-4132)
- Yi Liu (ORCID: https://orcid.org/0000-0002-2051-440X)
- Weiqing Wang (ORCID: https://orcid.org/0000-0001-6027-3084)
- Haoyu Liu
- Min Xu (ORCID: https://orcid.org/0000-0001-5135-6507)
- Mian Li (ORCID: https://orcid.org/0000-0001-6514-2729)
- Jie Zheng (ORCID: https://orcid.org/0000-0002-7961-6427)
- Hong Lin (ORCID: https://orcid.org/0000-0001-5860-4358)
- Jiying Qi (ORCID: https://orcid.org/0000-0002-4028-9713)
- Shan Luo (ORCID: https://orcid.org/0000-0002-8187-7001)
- Huiling Zhao
- Shuangyuan Wang (ORCID: https://orcid.org/0000-0002-1060-492X)
Institutions
- Shandong University (CN)
- Sun Yat-sen University (CN)
- University Hospitals Bristol NHS Foundation Trust (GB)
- Hong Kong Science and Technology Parks Corporation (HK)
- Ruijin Hospital (CN)
- University of Bristol (GB)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
- Chinese University of Hong Kong, Shenzhen (CN)
- State Key Laboratory of Oncogene and Related Genes (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-08-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101688
- Citations
- 19
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 6.80
Funders
- Wellcome Trust
- NIHR Bristol Biomedical Research Centre
- Cancer Research UK
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- Diabetes UK
- University of Bristol
- National Natural Science Foundation of China
- Shanghai Clinical Research Center
- Medical Research Council
- National Key Research and Development Program of China