The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data

Jie Zheng; Jieli Lu; Jiying Qi; Qian Yang; Huiling Zhao; Haoyu Liu; Zhihe Chen; Lanhui Huang; Youqiong Ye; Min Xu; Yu Xu; Tiange Wang; Mian Li; Zhiyun Zhao; Ruizhi Zheng; Shuangyuan Wang; Hong Lin; Chunyan Hu; Celine Sze Ling Chui; Shiu Lun Au Yeung; Shan Luo; Olympia Dimopoulou; Padraig Dixon; Sean Harrison; Yi Liu; Jamie Robinson; James Yarmolinsky; Philip Haycock; Jinqiu Yuan; Sarah Lewis; Zhongshang Yuan; Tom R. Gaunt; George Davey Smith; Guang Ning; Richard M. Martin; Bin Cui; Weiqing Wang; Yufang Bi

doi:10.1016/j.xcrm.2024.101688

The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data

Jie Zheng, Jieli Lu, Jiying Qi, Qian Yang, Huiling Zhao, Haoyu Liu, Zhihe Chen, Lanhui Huang, Youqiong Ye, Min Xu, Yu Xu, Tiange Wang, Mian Li, Zhiyun Zhao, Ruizhi Zheng, Shuangyuan Wang, Hong Lin, Chunyan Hu, Celine Sze Ling Chui, Shiu Lun Au YeungShan Luo, Olympia Dimopoulou, Padraig Dixon, Sean Harrison, Yi Liu, Jamie Robinson, James Yarmolinsky, Philip Haycock, Jinqiu Yuan, Sarah Lewis, Zhongshang Yuan, Tom R. Gaunt, George Davey Smith, Guang Ning, Richard M. Martin, Bin Cui, Weiqing Wang, Yufang Bi

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Summary 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.

Original language	English
Article number	101688
Pages (from-to)	101688
Number of pages	1
Journal	Cell Reports Medicine
Volume	5
Issue number	8
DOIs	https://doi.org/10.1016/j.xcrm.2024.101688
Publication status	Published - 20 Aug 2024

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Publisher Copyright:
© 2024 The Authors

Research Groups and Themes

ICEP

Keywords

SGLT2 inhibition
prostate cancer
Mendelian randomization
observational analysis
electronic healthcare records
cohort study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Zheng, J., Lu, J., Qi, J., Yang, Q., Zhao, H., Liu, H., Chen, Z., Huang, L., Ye, Y., Xu, M., Xu, Y., Wang, T., Li, M., Zhao, Z., Zheng, R., Wang, S., Lin, H., Hu, C., Chui, C. S. L., ... Bi, Y. (2024). The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data. Cell Reports Medicine, 5(8), 101688. Article 101688. https://doi.org/10.1016/j.xcrm.2024.101688

@article{c063047b19f54986b4ff78a93be757d6,

title = "The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data",

abstract = "Summary 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.",

keywords = "SGLT2 inhibition, prostate cancer, Mendelian randomization, observational analysis, electronic healthcare records, cohort study",

author = "Jie Zheng and Jieli Lu and Jiying Qi and Qian Yang and Huiling Zhao and Haoyu Liu and Zhihe Chen and Lanhui Huang and Youqiong Ye and Min Xu and Yu Xu and Tiange Wang and Mian Li and Zhiyun Zhao and Ruizhi Zheng and Shuangyuan Wang and Hong Lin and Chunyan Hu and Chui, {Celine Sze Ling} and Yeung, {Shiu Lun Au} and Shan Luo and Olympia Dimopoulou and Padraig Dixon and Sean Harrison and Yi Liu and Jamie Robinson and James Yarmolinsky and Philip Haycock and Jinqiu Yuan and Sarah Lewis and Zhongshang Yuan and Gaunt, {Tom R.} and Smith, {George Davey} and Guang Ning and Martin, {Richard M.} and Bin Cui and Weiqing Wang and Yufang Bi",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = aug,

day = "20",

doi = "10.1016/j.xcrm.2024.101688",

language = "English",

volume = "5",

pages = "101688",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "8",

}

Zheng, J, Lu, J, Qi, J, Yang, Q , Zhao, H, Liu, H, Chen, Z, Huang, L, Ye, Y, Xu, M, Xu, Y, Wang, T, Li, M, Zhao, Z, Zheng, R, Wang, S, Lin, H, Hu, C, Chui, CSL, Yeung, SLA, Luo, S, Dimopoulou, O, Dixon, P, Harrison, S, Liu, Y , Robinson, J , Yarmolinsky, J , Haycock, P, Yuan, J, Lewis, S, Yuan, Z, Gaunt, TR , Smith, GD, Ning, G, Martin, RM, Cui, B, Wang, W & Bi, Y 2024, 'The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data', Cell Reports Medicine, vol. 5, no. 8, 101688, pp. 101688. https://doi.org/10.1016/j.xcrm.2024.101688

TY - JOUR

T1 - The effect of SGLT2 inhibition on prostate cancer

T2 - Mendelian randomization and observational analysis using electronic healthcare and cohort data

AU - Zheng, Jie

AU - Lu, Jieli

AU - Qi, Jiying

AU - Yang, Qian

AU - Zhao, Huiling

AU - Liu, Haoyu

AU - Chen, Zhihe

AU - Huang, Lanhui

AU - Ye, Youqiong

AU - Xu, Min

AU - Xu, Yu

AU - Wang, Tiange

AU - Li, Mian

AU - Zhao, Zhiyun

AU - Zheng, Ruizhi

AU - Wang, Shuangyuan

AU - Lin, Hong

AU - Hu, Chunyan

AU - Chui, Celine Sze Ling

AU - Yeung, Shiu Lun Au

AU - Luo, Shan

AU - Dimopoulou, Olympia

AU - Dixon, Padraig

AU - Harrison, Sean

AU - Liu, Yi

AU - Robinson, Jamie

AU - Yarmolinsky, James

AU - Haycock, Philip

AU - Yuan, Jinqiu

AU - Lewis, Sarah

AU - Yuan, Zhongshang

AU - Gaunt, Tom R.

AU - Smith, George Davey

AU - Ning, Guang

AU - Martin, Richard M.

AU - Cui, Bin

AU - Wang, Weiqing

AU - Bi, Yufang

PY - 2024/8/20

Y1 - 2024/8/20

N2 - Summary 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.

AB - Summary 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.

KW - SGLT2 inhibition

KW - prostate cancer

KW - Mendelian randomization

KW - observational analysis

KW - electronic healthcare records

KW - cohort study

U2 - 10.1016/j.xcrm.2024.101688

DO - 10.1016/j.xcrm.2024.101688

M3 - Article (Academic Journal)

C2 - 39168098

SN - 2666-3791

VL - 5

SP - 101688

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 8

M1 - 101688

ER -

The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data

Abstract

Bibliographical note

Research Groups and Themes

Keywords

UN SDGs

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