Antidiabetic Medications and Bladder Cancer Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Yufeng Rao; Shiqiu Meng; Evan Yi-Wen Yu; Yiming Chen; Remigius van Alebeek; Abdulmohsen H Al-Zalabani; Maurice P Zeegers; Anke Wesselius

doi:10.1016/j.eprac.2025.11.017

Antidiabetic Medications and Bladder Cancer Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Endocr Pract. 2025 Dec 17:S1530-891X(25)01328-X. doi: 10.1016/j.eprac.2025.11.017. Online ahead of print.

Authors

Yufeng Rao¹, Shiqiu Meng², Evan Yi-Wen Yu³, Yiming Chen¹, Remigius van Alebeek⁴, Abdulmohsen H Al-Zalabani⁵, Maurice P Zeegers⁶, Anke Wesselius⁷

Affiliations

¹ Department of Epidemiology, Maastricht University, Maastricht, the Netherlands; Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
² Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.
³ Department of Epidemiology, Maastricht University, Maastricht, the Netherlands; Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing, China.
⁴ Maastricht University Library, Maastricht University, Maastricht, the Netherlands.
⁵ Department of Family and Community Medicine, College of Medicine, Taibah University, Madinah, Saudi Arabia.
⁶ Department of Epidemiology, Maastricht University, Maastricht, the Netherlands; Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
⁷ Department of Epidemiology, Maastricht University, Maastricht, the Netherlands; Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands. Electronic address: anke.wesselius@maastrichtuniversity.nl.

PMID: 41419174
DOI: 10.1016/j.eprac.2025.11.017

Abstract

Objective: The long-term safety of antidiabetic medications, particularly their potential association with bladder cancer (BC), remains a concern in type 2 diabetes mellitus (T2DM) management.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing antidiabetic medications to placebo in T2DM patients, focusing on BC outcomes. Database searched included PubMed, Embase (via OVID), Web of Science (Core Collection), Cochrane Library, and ClinicalTrials.gov up to 20 June 2025. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed using the I² statistic. Subgroup analyses were conducted by drug class ((dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1Ras), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), thiazolidinedione). Publication bias was assessed via funnel plot.

Results: Overall, antidiabetic medications were not significantly associated with an increased or decreased risk of BC (pooled OR = 0.90, 95% CI: 0.67-1.20; I² = 0.0%). Subgroup analyses by drug class also showed no statistically significant associations: DPP-4i (OR = 1.12, 95% CI: 0.67-1.85; I² = 0.0%), GLP-1Ras (OR = 0.72, 95% CI: 0.42-1.22; I² = 0.0%), and SGLT-2i (OR = 0.79, 95% CI: 0.50-1.24; I² = 0.0%). For thiazolidinediones, only one study (pioglitazone) reported an OR of 2.37 (95% CI: 0.91-6.17), which was not statistically significant. Funnel plots suggested no obvious publication bias.

Conclusions: This meta-analysis suggests that antidiabetic medications, including DPP-4i, GLP-1Ras, and SGLT-2i, are not significantly associated with BC risk in T2DM patients. These findings support the long-term safety profile of these medications.

Keywords: antidiabetic medications; bladder cancer; meta-analysis; randomized controlled trials; type 2 diabetes mellitus.

Publication types

Review