Type 2 diabetes is a disease where the body cannot properly regulate blood sugar levels. People with diabetes are at higher risk for many diseases, including some types of cancer. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a type of medication used to treat type 2 diabetes. These medications have been shown to have beneficial effects in patients with type 2 diabetes. In addition, there are recent laboratory studies suggesting that SGLT-2 inhibitors may be helpful for the prevention and treatment of lung cancer. To date, no studies in humans have studied the association between SGLT-2 inhibitors and the risk of lung cancer. To address this question, we will use the Clinical Practice Research Datalink to conduct a large cohort study to determine whether the use of SGLT-2 inhibitors is associated with a decreased risk of lung cancer. The findings of this study could have important implications for the prevention of lung cancer among patients with type 2 diabetes.
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are an approved second- to third-line treatment for type 2 diabetes. These drugs have been associated with improved glycaemic control, weight loss, and a decreased risk of cardiovascular outcomes. In addition to these beneficial effects, there is emerging evidence from laboratory studies that SGLT-2 inhibitors may have a beneficial role in the prevention and treatment of lung cancer. This is supported by studies reporting a high expression of SGLT-2 in premalignant lesions and adenocarcinomas of the lung.
We will use the United Kingdom Clinical Research Practice Datalink to assemble a cohort of patients aged 18 and older who were newly prescribed SGLT-2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between 1 January 2013 until 31 December 2019. Cox proportional hazards models with propensity score fine stratification weighting will be used to estimate hazard ratios and 95% confidence intervals of lung cancer incidence comparing SGLT-2 inhibitor users with DPP-4 inhibitor users. We will conduct secondary analyses to assess whether there is a duration-response relationship, whether the relationship varies by drug, and whether the association differs in smokers vs. non-smokers. The findings of this study could have relevant implications for the prevention of lung cancer among patients with type 2 diabetes.
The study outcome will be the first occurrence of an incident lung cancer during the follow-up period, which will be defined by Read and SNOMED-CT codes (see Appendix 1).
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
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Samantha Shapiro - Collaborator - McGill University