Assessing the association between incretin-based drugs and the incidence of colon cancer in patients with type 2 diabetes

Date of Approval: 
2016-12-20 00:00:00
Lay Summary: 
Globally, 415 million people currently live with diabetes. Of these, there are 3.9 million cases in the UK. As a highly prevalent disease, 12% of the global budget for health research is devoted to diabetes, and through this research there have been many drugs developed to treat type 2 diabetes. A newer class of drugs, the incretin-based drugs, were introduced into the UK market in 2007. These drugs have been found to assist in weight loss, while lowering blood sugar to optimal levels. However, there are some concerns that the incretin-based drugs might increase the risk of colon cancer. To date no study has investigated the association between incretin-based drugs and colon cancer. Given the popularity of incretin-based drugs in the type 2 diabetic population, there is an urgent need to assess this risk. This study will investigate whether the use of incretin-based drugs is associated with an increased risk of colon 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: 
The literature offers discrepant findings as to whether the use of incretin-based drugs is associated with colon cancer incidence. There is evidence that the GLP-1 pathway may be involved in the development of colon cancer by promoting gut growth and crypt fission. However, in a post-hoc analysis of the SAVOR-TIMI 53 trial, the use of the DPP-4i, saxaglipitin, was associated with a 49% decreased risk of colon cancer. Further investigation is required to determine the true association. This study will assess this association by assembling a cohort of patients, at least 40 years of age, newly-treated with antidiabetic drugs between January 1, 1988 and March 31, 2015, with follow up until March 31, 2016. The use of incretin based drugs will be modelled as a time-varying variable, where patients will be considered unexposed to incretin-based drugs until one year after the first prescription for latency purposes. Time-dependent Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of colon cancer associated with the use of incretin-based drugs. Secondary analyses will assess whether the risk varies by class (DPP-4i vs. GLP-1a), according to cumulative duration of use, or according to time since initiation.
Health Outcomes to be Measured: 
Incidence of colon cancer in patient with type 2 diabetes.
Application Number: 
16_264
Collaborators: 

Samy Suissa - Chief Investigator - McGill University
Laurent Azoulay - Corresponding Applicant - McGill University
Devin Abrahami - Collaborator - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Michael Pollak - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital