Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: A population-based cohort study

Chou, Oscar Hou In; Lu, Lei; Chung, Cheuk To; Chan, Jeffrey Shi Kai; Chan, Raymond Ngai Chiu; Lee, Athena Yan Hiu; Dee, Edward Christopher; Ng, Kenrick; Pui, Hugo Hok Him; Lee, Sharen; Cheung, Bernard Man Yung; Tse, Gary; Zhou, Jiandong

doi:10.1016/j.diabet.2024.101571

Diabetes & Metabolism

2025

DOI: 10.1016/j.diabet.2024.101571

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Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: A population-based cohort study

Oscar Hou In Chou,

Lei Lu,

Cheuk To Chung

et al.

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Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study

Shen,

Yang,

et al. 2024

Preprint

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BackgroundEpidemiological studies have linked the use of the anti-diabetic medications, sodium-glucose co-transporter-2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) and glucagon-like peptide-1 receptor agonists (GLP1RA), with prostate cancer risk. However, these studies cannot infer causality.MethodsThis was a two-sample Mendelian randomization (MR) using genome-wide association study data designed to identify causal relationships between SGLT2I, DPP4I or GLP1RA and prostate cancer. Genetic associations with HbA1c and risk of prostate cancer were extracted from IEU Open-GWAS Project database with GWAS id ukb-d-30750_irnt (UK Biobank cohort) and ebi-a-GCST006085 (European Molecular Biology Laboratory’s European Bioinformatics Institute cohort), respectively. The two GWAS datasets chosen were obtained from individuals of European ancestry to minimise potential bias from population stratification. The encoding genes targeted by SGLT2I, DPP4I and GLP1RA were SGC5A2, DPP4 and GLP1R, located in Chr16: 31494323-31502181, Chr2: 162848755-162930904 and Chr6: 39016557-39059079, respectively.ResultsA total of 31, 2 and 5 single nucleotide variants (SNVs) were used for SGC5A2, DPP4 and GLP1R. Our MR analysis results supported a causal relationship between genetic variation in SLC5A2 and DPP4 and reduced risk of prostate cancer at the Bonferroni-corrected threshold, with odds ratios (OR) [95% confidence intervals] of 0.47 [0.38-0.58] and 0.35 [0.24-0.53], but not for GLP1R (OR: 1.39 [0.93-2.07]). Sensitivity analyses by the leave-one-out method did not significantly alter the OR for SGLT2I.ConclusionsThe two-sample MR analysis found that SGLT2 and DPP4 inhibition, but not GLP1R agonism, was associated with lower risks of developing prostate cancer.

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Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study

Shen,

Yang,

et al. 2024

Preprint

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Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: A population-based cohort study

Cited by 1 publication

References 43 publications

Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study

Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study

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