Abstract

Purpose
Preclinical studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT-2is) may have cancer-preventive effects; however, clinical evidence remains inconclusive. Therefore, this study aimed to evaluate the association between the use of SGLT-2is (empagliflozin or dapagliflozin) and the incidence of new-onset cancer in patients with type 2 diabetes.
Materials and Methods
This nationwide retrospective cohort study used Korean national health claims data. Patients with type 2 diabetes who started empagliflozin, dapagliflozin, or other glucose-lowering drugs (oGLDs) between 2016 and 2019 were included, and propensity score matching between the SGLT-2is users and oGLDs users was applied. The primary outcome was overall cancer incidence, and the secondary outcomes were the incidence of 11 site-specific cancers. Hazard ratios (HRs) and confidence intervals (CIs) for cancer incidence adjusted for covariates were estimated using a Cox proportional hazards model.
Results
After propensity score matching, each group comprised 20,456 patients. There was no significant difference in the overall incidence of new-onset cancer in either the empagliflozin or dapagliflozin groups when compared to the oGLDs user group (adjusted HR 0.85, 95% CI 0.65–1.12; adjusted HR 0.87, 95% CI 0.66–1.14, respectively). Similar results were observed in site-specific cancer incidence. Furthermore, there were no significant differences in overall or site-specific cancer incidence between the empagliflozin and dapagliflozin user groups. The results were consistent across subgroup analyses and various sensitivity analyses.
Conclusion
In this large-scale national cohort study, the use of empagliflozin or dapagliflozin did not show a significant difference in the incidence of new-onset cancer in patients with type 2 diabetes. These results provide evidence supporting the association between SGLT-2i use and cancer risk in this population, based on real-world clinical data. Longer-term follow-up studies would be helpful in strengthening the validity of these findings.

• Keywords: Neoplasms, Incidence, Sodium-glucose transporter 2 inhibitors, Dapagliflozin, Empagliflozin, Diabetes Mellitus, Type 2, Cohort studies