Survival association of GLP-1 receptor agonists and SGLT2 inhibitors in bladder cancer patients

OBJECTIVES: To evaluate whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1) or sodium-glucose cotransporter 2 inhibitors (SGLT2) is associated with overall survival (OS) in adults with treated bladder cancer. SUBJECTS/PATIENTS AND METHODS: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX Global Collaborative Network (2013-2024). Adults with bladder cancer receiving surgery, chemotherapy, and/or radiotherapy were classified as GLP-1 receptor agonist- or SGLT2 inhibitor-exposed vs. nonexposed (mutual class exclusion). Treatment had to occur within ±3 months of the bladder cancer criterion for GLP-1 receptor agonist and within ±3 months for SGLT2 inhibitors. Exposed and nonexposed cohorts were propensity-score matched 1:1 on demographics, comorbidities, and concomitant medications. OS was assessed from day 1 through day 3650 after the index event. RESULTS: After matching, 5,294 GLP-1 receptor agonist users were compared with 5,294 nonusers, and 5,356 SGLT2 inhibitor users with 5,356 nonusers. Mortality was lower with GLP-1 receptor agonist exposure (934 vs. 1,855 deaths; hazard ratio for nonuse vs. use 1.915, 95% CI, 1.770-2.073; P < 0.001) and with SGLT2 inhibitor exposure (1,325 vs. 2,099 deaths; hazard ratio 1.232, 95% CI, 1.148-1.322; P < 0.001). In 6- and 12-month landmark sensitivity analyses the associations attenuated but remained statistically significant. CONCLUSION: In these large, propensity-matched, multicenter real-world cohorts of treated bladder cancer, GLP-1 receptor agonist and SGLT2 inhibitor exposure were each associated with improved OS. Limitations include residual confounding and limited granularity for tumor stage and treatment intent; prospective and mechanistic studies are needed to assess causality and clinical utility.