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

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, andClinicalTrials.govup 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 I²statistic. 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.