Currently 3.9 million people are living with diabetes in the UK, with this number predicted to rise to 5 million by 2025. Recent evidence suggests that individuals with diabetes may be at risk of developing several types of cancers including bowel and bladder cancer. Furthermore, evidence suggests metformin, a first line therapy for type 2 diabetes, may reduce the risk of several cancers, including breast cancer. However for other types of cancer evidence is limited and inconclusive, including for a group of cancers whose development is triggered by certain viruses. These cancers account for approximately 10% of all cancers worldwide and include for example cancer of the liver and cervix. This study will investigate if the use of metformin is associated with a decrease in risk of virus-induced cancers in patients with type 2 diabetes using the Clinical Practice Research Datalink.
Recently, there has been an interest in the anti-tumor effects of metformin, a biguanide used in the treatment of type 2 diabetes. Preclinical studies suggest metformin may have anti-tumor effects on viral induced cancers yet limited observational studies to date have investigated this. This study aims to investigate if metformin is associated with a decreased risk of vial induced cancers. From a cohort of patients newly-prescribed non-insulin antidiabetic medications between January 1 1988 and March 31 2015, all patients with type 2 diabetes (with no prior history of cancer) will be identified. All patients will be followed-up until a first diagnosis of viral-induced cancer or censored upon hysterectomy (with a 3 month window to allow the inclusion of any cervical cancer diagnoses determined at hysterectomy), a death (from any cause), end of registration with the GP or end of the study period (March 31 2016). Time-dependent Cox proportional hazard models will be used to estimate HRs and 95% CIs of viral-induced cancer associated with the use of metformin compared to the use of other diabetic medications. Secondary analyses will investigate cumulative duration of use and cancer site specific associations.
Primary outcome: a primary diagnosis of selected viral-induced cancers as a composite outcome (including hepatocellular carcinoma, Kaposi sarcoma, T-cell leukaemia, Non-Hodgkin's lymphoma, cervical cancer, anal cancer, penile cancer, vaginal cancer, vulvar cancer, and oropharyngeal cancer). Secondary outcomes: site-specific viral-induced cancers.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Blánaid Hicks - Collaborator - Queen's University Belfast
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Collaborator - McGill University
Liliya Sinyavskaya - Collaborator - McGill University
Paul Brassard - Collaborator - McGill University