Non-alcoholic fatty liver disease (NAFLD) is a common liver disease among patients with type 2 diabetes. It is responsible for significant health problems, including long term illnesses such as cirrhosis and liver cancer. Thus, it is important to find new ways to prevent the development of NAFLD in patients with type 2 diabetes. Previous research suggests that drugs such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce liver fat. However, no study has examined whether these drugs are able to prevent NAFLD among those not yet diagnosed with the disease. The current study will use the United Kingdom Clinical Practice Research Datalink to investigate whether the use of GLP-1 RAs and SGLT-2 inhibitors, compared with another antidiabetic drug class, dipeptidyl peptidase-4 (DPP-4) inhibitors, decreases the risk of being diagnosed with NAFLD. This will provide much needed information regarding this possible association to patients and prescribers.
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.
Non-alcoholic fatty liver disease (Read codes and SNOMED-CT concept IDs outlined in Appendix 1).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
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