Incretin-based drugs, which include glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, are commonly-used drugs for the treatment of type 2 diabetes. While these drugs have been shown to have beneficial effects, there are concerns that their use might increase the risk of intestinal obstruction (a condition characterized by a blockage in the small or large intestine). To date, however, it remains unknown whether these drugs are associated with an increased risk of intestinal obstruction, compared with other antidiabetic drugs. As intestinal obstruction can be a serious medical condition, the goal of this study is to evaluate this possible association using a large population-based cohort of patients treated for type 2 diabetes.
Incretin-based drugs, which include glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, are commonly used drugs in the treatment of type 2 diabetes. While these drugs have been shown to have favourable clinical effects, there are concerns that they might increase the risk of intestinal obstruction.
Incretin-based drugs can reduce gastrointestinal motility by either directly binding to GLP-1 receptors in the gut (GLP-1 RAs) or by increasing physiologic levels (DPP-4 inhibitors) of GLP-1. Indeed, several cases of ileus or intestinal obstruction in patients exposed to incretin-based drugs have been reported in postmarketing surveillance. However, to date, no observational study has been conducted to assess this possible association. Thus, the objective of this study is to determine whether use of incretin-based drugs (GLP-1 RAs and DPP-4 inhibitors, separately) are associated with an increased risk of intestinal obstruction, compare with use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Using the Clinical Practice Research Datalink, Hospital Episodes Statistics repository, and Office for National Statistics databases, we will select new users of incretin-based drugs which will be compared with new users of SGLT-2 inhibitors from January 1, 2013 to December 31, 2018, with follow-up until April 30, 2019. Patients will be followed while continuously exposed to the drugs until the occurrence of a hospitalization for intestinal obstruction, death from any cause, end of registration with the general practice, or end of study (April 30, 2019). We will use propensity score fine stratification to control for confounding, and Cox proportional hazard models will be used to estimate the hazard ratios (with 95% confidence intervals) of intestinal obstruction comparing GLP-1 RAs and DPP-4 inhibitors with SGLT-2 inhibitors.
The outcome will consist of a hospitalization for non-mechanical intestinal obstruction (or ileus) or severe constipation requiring a hospitalization. Specifically, the outcome will be defined as a hospitalization with a primary or secondary diagnosis of intestinal obstruction, or a primary diagnosis of constipation, as determined by pre-specified ICD-10 codes.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Astrid Herrero - Collaborator - Montpellier University Hospital
Christel Renoux - Collaborator - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Jean-Luc Faillie - Collaborator - Montpellier University Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Romain Altwegg - Collaborator - Montpellier University Hospital
HES Admitted Patient Care;ONS Death Registration Data