The risk of bladder cancer in type 2 diabetes mellitus with combination therapy of sglt-2 inhibitors and pioglitazone

Yan Rong Li, Chi Hung Liu, Wei Chiao Sun, Pei Yi Fan, Feng Hsuan Liu, Tien Hsing Chen, Victor Chien Chia Wu, Chihung Lin*, Ching Chung Hsiao*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations


Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70; 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94; group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99; group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality.

Original languageEnglish
Article number828
JournalJournal of Personalized Medicine
Issue number9
StatePublished - 09 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Bladder cancer
  • Mortality
  • Pioglitazone
  • Sodium glucose cotransporter-2 (SGLT-2) in-hibitors
  • Type 2 diabetes mellitus


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