SGLT2 Inhibitor Use and Risk of Breast Cancer Among Adult Women with Type 2 Diabetes

Introduction Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic agents, with the potential to inhibit breast cancer development. However, the association between SGLT2 inhibitors and risk of breast cancer in human studies is unclear. Objective The aim of our study is to use a large national claims database to assess the association between SGLT2 inhibitor use and risk of breast cancer. Methods We considered a study population of 158,483 adult women with type 2 diabetes who newly initiated SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP4) inhibitors using Optum’s deidentified Clinformatics Data Mart Database between 1 January 2013 and 31 March 2022. The association between SGLT2 inhibitor use and risk of breast cancer was examined using Cox proportional hazard models stratified by age in the overall sample and in a subsample based on propensity score and medication initiation time matching. The effect of medication use duration was explored. Results With an average follow-up of 2.2 years, 2154 breast cancer cases were identified. There was no significant association between SGLT2 inhibitor use and the risk of breast cancer in overall sample (HR = 0.96; 95% CI 0.87, 1.06), in women younger than 51 years old (HR = 0.88; 95% CI 0.59, 1.32), or in women aged 51 years or older (HR = 0.95; 95% CI 0.86, 1.04). The results remained nonsignificant using matching, medication use duration, and sensitivity analyses. Conclusion Our findings suggest SGLT2 inhibitors use was not associated with breast cancer risk compared with DPP4 inhibitors use. Studies with longer follow-up and better adjustments are needed to confirm the finding.