Glucagon-like peptide-1 receptor agonists and the risk of gastro-oesophageal reflux disease in patients with type 2 diabetes

Study type
Protocol
Date of Approval
Study reference ID
24_004150
Lay Summary

Gastroesophageal reflux disease (GERD) is a common condition in which the stomach contents move back up from the stomach into the oesophagus (a tube that connects the mouth and the stomach). Patients with high blood sugar levels have a higher risk of developing GERD compared to those without. There is a rising concern that a common blood sugar-lowering drug, called glucagon-like peptide-1 receptor agonists (GLP-1 RAs), may increase the risk of developing GERD because it makes food stay in the stomach for longer periods and can cause food to reflux from the stomach; however, the available evidence on this is sparse. In the current study, we will use data from the Clinical Practice Research Datalink database to assess whether the use of GLP-1 RAs is associated with an increased risk of GERD, compared with the use of another blood sugar-lowering drug class, sodium-glucose cotransporter-2 (SGLT-2) inhibitors. This study will provide information that enables clinicians and patients to make a more informed decision when deciding on the most appropriate medication in patients with high blood sugar levels.

Technical Summary

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are being increasingly prescribed among patients with type 2 diabetes. Concerns are being raised about the delayed gastric emptying effect of GLP-1 Ras, resulting in gastro-oesophageal reflux disease (GERD); however, the available evidence remains scarce. Thus, the objective of this population-based study is to determine whether the use of GLP-1 RAs is associated with an increased risk of GERD when compared with the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors among patients with type 2 diabetes. To address this objective, we will use the Clinical Practice Research Datalink database to identify patients at least 18 years of age newly treated with a GLP-1 RA or an SGLT-2 inhibitor between January 1, 2013 and December 31, 2021. Cox proportional hazard models will be used to estimate hazard ratios with 95% confidence intervals of GERD and its severe complications associated with GLP-1 RAs compared with SGLT-2 inhibitors. Secondary analyses will assess whether there is a duration-response relation, and whether the risk varies by individual GLP-1 RAs and patient characteristics, such as age, sex, body mass index, smoking status, duration and severity of diabetes, and specific comorbidities and drug use. This study will provide much needed information on increasingly prescribed GLP-1 RAs and their safety among patients with type 2 diabetes.

Health Outcomes to be Measured

Gastro-oesophageal reflux disease (GERD) (based on Read codes and SNOMED-CT concept IDs outlined in Appendix 1).

Collaborators

Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Alain Bitton - 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
Yunha Noh - Collaborator - Sungkyunkwan University