Sodium-glucose transport protein (SGLT-2) inhibitors are a new class of drugs used for the treatment of type 2 diabetes. These drugs offer several benefits such as reducing blood sugars, weight loss and lowering of blood pressure. More importantly, they have been shown to reduce the risk of heart attacks, stroke, and death. However, there have been concerns that SGLT-2 inhibitors may be associated with breast cancer diagnosed relatively soon after the start of treatment. To date, no real-world study has been conducted to assess this safety question. Thus, we will conduct a large study to determine whether the use of SGLT-2 inhibitors is associated with an increased risk of early breast cancer. Our study will provide the necessary information to better assess the risk and benefits of this treatment in patients with type 2 diabetes.
Current guidelines recommend sodium-glucose transport protein 2 (SGLT-2) inhibitors as second line therapy for patients with type 2 diabetes. SGLT-2 inhibitors act on the kidney to inhibit the sodium-glucose protein 2, thereby allowing the excretion of glucose in the urine (glycosuria) and the lowering of plasma glucose levels. However, the US Food and Drug Administration and the European Medicines Agency have raised concerns that certain SGLT-2 inhibitors, such as dapagliflozin, have been associated with early breast cancer events in premarketing trials. To date, however, no observational studies have been conducted to assess this possible increased risk in the real-world setting. Thus, to address this concern, we will conduct a large population-based cohort study to assess whether SGLT-2 inhibitors are associated with an increased risk of early breast cancer. The study population will consist of women over 40 years of age newly treated with SGLT-2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors. Each patient will be followed until a first diagnosis of breast cancer, death from any cause, end of registration with the general practice, or end of study (January 31, 2019). We will use propensity score fine stratification to minimize potential confounding, and Cox proportional hazard models will be used to estimate the hazard ratios (with 95% confidence intervals [CI]) of breast cancer comparing SGLT-2 inhibitors users and DPP-4 inhibitors users. This large cohort study will provide the necessary information on the risks and benefits of SGLT-2 inhibitors.
The primary outcome of interest is a diagnosis of breast cancer, as determined by pre-specified CPRD Read Codes (listed in Appendix 2).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Melanie Suissa - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Stephanie Wong - Collaborator - McGill University