Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new drugs for the treatment of diabetes. First introduced in the United Kingdom in 2007, these drugs have become increasingly popular because they effectively lower glucose levels in the blood, but without the side effects of other antidiabetic drugs. In addition to their effects on lowering glucose levels, there is some evidence that these drugs may play a role in inflammatory bowel disease (IBD), a chronic disease that affects the digestive tract. However, the exact role of these drugs on this disease remains unclear. Moreover, to date, no studies have been conducted to assess whether the use of DPP-4 inhibitors affects the risk of developing IBD. Thus, using the Clinical Practice Research Datalink, we will assemble a large group of patients with type 2 diabetes to assess this association. This will provide much needed information on the safety of DPP-4 inhibitors.
DPP-4 inhibitors are incretin-based drugs that are now commonly used to treat type 2 diabetes. However, in addition to its role in glucose metabolism, there is evidence that the DPP-4 enzyme (also known as CD26) may play a role in IBD, although its specific role is not well understood. On the one hand, this enzyme has been shown to inhibit T-cell proliferation and cytokine production, while on the other, studies have reported decreased levels of the DPP-4 enzyme in serum of IBD patients, which are inversely associated with disease severity; the latter supports a possible deleterious role of DPP-4 in IBD. To address this question, we will assemble a cohort of approximately 130,000 patients newly-treated with antidiabetic drugs between 2007 and 2016, with follow up until 2017. Use of DPP-4 inhibitors will be modelled as a time-varying variable, allowing for a 6-month lag period for latency. Time-dependent Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of IBD associated with use of DPP-4 inhibitors, compared with use of all other antidiabetic drugs. Secondary analyses will assess whether risk varies by duration of use, and by type of IBD (Crohn's disease and ulcerative colitis).
Inflammatory bowel disease (IBD) overall; Crohn's disease; Ulcerative colitis.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Alain Bitton - Collaborator - McGill University
Antonios Douros - Collaborator - McGill University
Christel Renoux - Collaborator - McGill University
Devin Abrahami - Collaborator - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital