We propose to conduct a study to assess whether the use of incretin-based drugs, in comparison with the use of SGLT-2 inhibitors, antidiabetic drugs used at a similar stage in the disease, is associated with an increased risk of acute liver injuries among patients with type 2 diabetes mellitus. We will assemble a cohort of patients, at least 18 years of age, who initiated incretin-based drugs or SGLT-2 inhibitors from 1 January 2013 (the year of availability of the comparator drugs in the United Kingdom) until 31 December 2019, with follow-up until March 31, 2020. Propensity scores will be computed to determine the predicted probability of treatment with GLP-1 RAs or DPP-4 inhibitors versus SGLT-2 inhibitors. Cox proportional hazards models with propensity score fine stratification weighting will then be used to estimate hazard ratios of acute liver injury, separately for GLP-1 RAs and DPP-4 inhibitors. Secondary analyses will be conducted to determine whether there is a duration-response relation, association with individual drugs, and whether the association varies by age, sex, and use of hepatotoxic drugs. Given the relatively high prevalence of type 2 diabetes, our study will address an important safety concern regarding the commonly used drugs in this patient population.
Acute liver injury identified by using Read and SNOMED-CT codes as well as a liver-enzyme based definition in CPRD,1, 2 and ICD-10 codes3 in HES and ONS (definitions in Appendix 1).
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
HES Admitted Patient Care;ONS Death Registration Data