A recent study by Devin Abrahami published in the journal of Diabetes Care found that sodium-glucose cotransporter 2 (SGLT2) inhibitors are not associated with an increase in bladder cancer risk (early bladder cancer events) when compared with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4 inhibitors).

From January 2013 to December 2020, researchers conducted an extensive multi-site, population-based, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum's de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases. Adult patients with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors are assembled for this study. To estimate hazard ratios (HRs), Cox proportional hazards models were utilized and 95% CIs of incident bladder cancer. Further the models were weighted using propensity score fine stratification.

The highlights of the study were:
1. A total of 4,53,560 and 3,75,997 adults were included in the SGLT2 inhibitor group and GLP-1RA group respectively. The users had a median follow-up from 1.5 to 2.2 years.
2. The overall results suggest that SGLT2 inhibitors were not associated with an increased bladder cancer risk compared with the GLP-1RAs (HR 0.90, 95% CI 0.81–1.00).
3. When compared with DPP-4 inhibitors (n = 853,186), the SGLT2 inhibitors (n = 347,059) were not associated with a hike in bladder cancer risk (HR 0.99, 95% CI 0.91–1.09) with a median follow-up from 1.6 to 2.6 years. In the sensitivity analyses the results were consistent thorough out.
The Authors found that SGLT2 inhibitors did not impact negatively in inducing bladder cancer risk. The findings further suggest that the short-term usage of SGLT2 inhibitors did not hinder bladder cancer incidence.
Reference:
Abrahami, D., Tesfaye, H., Yin, H., Vine, S., Hicks, B., Yu, O. H. Y., Campeau, L., Platt, R. W., Schneeweiss, S., Patorno, E., & Azoulay, L. (2022). Sodium–Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study. In Diabetes Care. American Diabetes Association. https://doi.org/10.2337/dc22-1174