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The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2024 Aug 20; Vol. 5 (8), pp. 101688. - Publication Year :
- 2024
-
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 (n <subscript>SGLT2i</subscript>  = 24,155; n <subscript>DPP4i</subscript>  = 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 <subscript>4C</subscript>  = 57,779; n <subscript>UK&#95;Biobank</subscript>  = 165,430), we found little evidence to support the association of HbA <subscript>1c</subscript> 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.<br />Competing Interests: Declaration of interests G.D.S. reports scientific advisory board membership for Relation Therapeutics and Insitro. UK Biobank has received ethical approval from the UK National Health Service’s National Research Ethics Service (ref. 11/NW/0382). All other studies contributing data to this analysis had the relevant institutional review board approval from each country and all participants provided informed consent.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Male
Middle Aged
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 genetics
Cohort Studies
Aged
Glycated Hemoglobin metabolism
Sodium-Glucose Transporter 2 metabolism
Sodium-Glucose Transporter 2 genetics
Electronic Health Records
Prostatic Neoplasms genetics
Prostatic Neoplasms drug therapy
Mendelian Randomization Analysis
Sodium-Glucose Transporter 2 Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39168098
- Full Text :
- https://doi.org/10.1016/j.xcrm.2024.101688