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Updated: Jun 15, 2025
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using
Jie Zheng1, Jieli Lu2, Jiying Qi2
1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Abstract:
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 (nSGLT2i = 24,155; nDPP4i = 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 (n4C = 57,779; nUK_Biobank = 165,430), we found little evidence to support the association of HbA1c 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.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibition shows a reduced risk of prostate cancer, including advanced and early-onset forms. This suggests SGLT2 inhibitors may offer benefits for prostate cancer prevention.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Prostate cancer remains a significant health concern globally.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are primarily used for diabetes management.
- The potential impact of SGLT2 inhibition on prostate cancer risk is an emerging area of research.
Purpose of the Study:
- To evaluate the effect of SGLT2 inhibition on prostate cancer risk using multiple lines of evidence.
- To investigate whether the effects are mediated by glycemic control.
Main Methods:
- Mendelian randomization analysis using large-scale genetic data.
- Retrospective analysis of electronic healthcare records.
- Prospective cohort studies including UK Biobank and 4C.
Main Results:
- Genetically proxied SGLT2 inhibition was associated with reduced risk of overall, advanced, and early-onset prostate cancer.
- SGLT2 inhibitor use in men with diabetes was linked to a 23% lower risk of prostate cancer.
- Limited evidence supported a link between HbA1c and prostate cancer, suggesting a non-glycemic mechanism for SGLT2 inhibition's effect.
Conclusions:
- This study provides robust evidence supporting a beneficial role of SGLT2 inhibition in reducing prostate cancer risk.
- The findings suggest a potential non-glycemic mechanism underlying this protective effect.
- Further clinical trials are recommended to explore SGLT2 inhibitors for prostate cancer prevention.
