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SGLT2 inhibition and three urological cancers: Up-to-date results

Lede Lin1, Kang Ning2,3, Liyuan Xiang4

  • 1Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Diabetes/Metabolism Research and Reviews
|March 25, 2024
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibition does not increase the risk of bladder, prostate, or kidney cancer. In fact, SGLT2 inhibition may offer protective effects against these urological cancers.

Area of Science:

  • Urology
  • Oncology
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications primarily used for managing type 2 diabetes.
  • Emerging evidence suggests potential pleiotropic effects of SGLT2 inhibition beyond glycemic control, prompting investigation into their impact on various organ systems, including the urinary tract.

Purpose of the Study:

  • To investigate the potential causal relationship between SGLT2 inhibition and the risk of developing three common urological cancers: bladder, prostate, and kidney cancer.
  • To utilize Mendelian randomization and in vitro analyses to establish or refute a causal link.

Main Methods:

  • Employed Mendelian randomization using six single nucleotide polymorphisms (SNPs) in SLC5A2 as a proxy for SGLT2 inhibition.
  • Analyzed large-scale cohorts for bladder cancer (UK Biobank), prostate cancer (PRACTICAL consortium), and kidney cancer (UK Biobank).
  • Conducted primary and sensitivity analyses, supplemented with in vitro validation, to ensure the robustness of the findings.

Main Results:

  • SGLT2 inhibition was associated with a reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97-0.99) per unit lowering of HbA1c.
  • A significant protective association was observed for prostate cancer (OR: 0.31, 95% CI: 0.21-0.47).
  • No causal relationship was found between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99-1.00). Sensitivity analyses and in vitro data did not support a causal role in increasing cancer risk.

Conclusions:

  • There is no evidence to suggest that SGLT2 inhibition increases the risk of bladder, prostate, or kidney cancer.
  • Findings indicate a potential protective effect of SGLT2 inhibition against these urological malignancies.
  • Further research is warranted to fully elucidate the oncoprotective mechanisms of SGLT2 inhibitors in the urological system.
Keywords:
SGLT2 inhibitionbladder cancerkidney cancerprostate cancer

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