Use of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors for the Prevention of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes

Date of Approval
Application Number
21_000458
Technical Summary

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, by virtue of weight-reducing and anti-inflammatory effects, have been shown to reduce liver fat and resolve hepatic inflammation. However, whether these drugs reduce the risk of NAFLD in patients with type 2 diabetes in the real-world setting is unclear. Accordingly, in this population-based cohort study, we will compare the incidence of NAFLD among new users of GLP-1 RAs and SGLT-2 inhibitors, separately, with new users of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes. Thus, this study will use the Clinical Practice Research Datalink to assemble two new-user, active comparator cohorts of patients at least 40 years of age, one comprising of new users of GLP-1 RA and DPP-4 inhibitors between January 1, 2007 and April 30, 2020, and the other comprising of new users of SGLT-2 inhibitors and DPP-4 inhibitors between January 1, 2013 and April 30, 2020. Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of NAFLD associated with GLP-1 RAs and SGLT-2 inhibitors compared with DPP-4 inhibitors. Secondary analyses will assess whether there is a duration-response relation, and whether there is effect measure modification by age, sex, use of lipid lowering agents, and body mass index.

Health Outcomes to be Measured

Non-alcoholic fatty liver disease (Read codes and SNOMED-CT concept IDs outlined in Appendix 1).

Collaborators

Samy Suissa - Chief Investigator - McGill University
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
Richeek Pradhan - Collaborator - Sir Mortimer B Davis Jewish General Hospital