GLP-1 agonists and the risk of breast cancer in patients with type 2 diabetes

Date of ISAC Approval: 
14/06/2016
Lay Summary: 
Currently 3.9 million people in the UK have diabetes, with this number predicted to rise to 5 million by 2025. First introduced in the UK in 2007, glucagon-like peptide-1 (GLP-1) agonists are second- to third-line therapies used in the treatment of type 2 diabetes. While these therapies have been shown to be effective in treating type 2 diabetes and inducing weight loss, there are emerging concerns that these drugs may increase the risk of breast cancer. To date, no study conducted in the real-world setting has been conducted to assess this association Such studies are urgently needed to assess if this risk is substantiated. This study will investigate whether the use of GLP-1 agonists is associated with an increased risk of breast cancer in patients with type 2 diabetes using the Clinical Practice Research Datalink. This study will provide much needed information of this potential association, which will be of value to regulatory agencies, physicians, and patients.
Technical Summary: 
Recent evidence from preclinical studies and randomised controlled trials suggest that GLP-1 agonists may increase the risk of breast cancer. However, to date, no observational study has investigated this potential safety issue. Thus, the objective of this study will be to assess this association by assembling a cohort of female patients who initiated a new antidiabetic drug class on or after January 1, 2007 until March 31, 2015. All patients will be followed until a first-ever diagnosis of breast cancer, or censored upon death, end of registration with the practice, or end of the study period (March 31, 2016). Time-dependent Cox proportional hazard models will be used to estimate hazard ratios and 95% confidence intervals of breast cancer associated with the use GLP-1 agonists when compared with the use of DPP-4 inhibitors, with exposures lagged by 1 year for latency purposes. Secondary analyses will assess whether the risk varies according to cumulative duration of use and time since initiation. This study will provide the concerned stakeholders with the necessary information to assess the risks and benefits of these therapies.
Health Outcomes to be Measured: 
Primary diagnosis of breast cancer (malignant and carcinoma in situ)
Collaborators: 

Samy Suissa - Chief Investigator - McGill University
Blanaid Hicks - Collaborator - Queens University Belfast
Hui (Hoi) Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Dr Laurent Azoulay - Collaborator - McGill University
Michael Pollak - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Dr Robert Platt - Collaborator - McGill University
Dr Robert Platt - Researcher - McGill University
Samy Suissa - Corresponding Applicant - McGill University