Comparison of the Risk of Acute Liver Injury Between Patients With Type 2 Diabetes Exposed to Dapagliflozin and Those Exposed to Other Antidiabetic Treatments

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  XIGDUO
• Name of medicine, other:
  Farxiga
• Study drug International non-proprietary name (INN) or common name:
  DAPAGLIFLOZIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A10BD14) metformin and repaglinide

  metformin and repaglinide
• Medical condition to be studied:
  Acute hepatic failure

Population studied

• Short description of the study population:
  The study focused on risk of acute liver injury in patients with type 2 diabetes aged 18 years or more exposed to dapagliflozin and other antidiabetic (ADs) treatments identified from CPRD, HIRD and Medicare database in the US.; Inclusion criteria:; (1) receive newly prescribed dapagliflozin (with or without other ADs) or a newly prescribed AD (with or without other ADs) in a class other than SGLT2 inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy; ; (2) do not have evidence of type 1 diabetes; ; (3) are aged 18 years or older at the index date for CPRD patients, 18-64 years for HIRDSM patients, or 65 years or older for Medicare patients; and ; (4) have been enrolled in the data source for at least 180 days before the first prescription or dispensing for dapagliflozin or comparator AD. ; ; Exclusion criteria: ; Patients with a previous diagnosis of ALI; liver, biliary, or pancreatic disease; hepatobiliary or pancreatic neoplasm; or congestive heart failure will be excluded.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with type 2 diabetes mellitus
• Estimated number of subjects:
  459636

Study design details

• Main study objective:
  To compare, by insulin use at the index date, the incidence of hospitalization for acute liver injury (ALI) among patients with type 2 diabetes mellitus who are new users of dapagliflozin to those who are new users of ADs in classes other than sodium-glucose cotransporter 2 (SGLT2) inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy.
• Outcomes:
  acute liver injury
• Data analysis plan:
  Descriptive statistics will be calculated to compare baseline characteristics at cohort entry between dapagliflozin users versus comparator antidiabetic users. Propensity scores will be estimated by using logistic regression, with measured potential predictors of acute liver injury as independent variables in the regression model and actual exposure group (dapagliflozin or comparator) as the outcome. Incidence rates of acute liver injury will be estimated during exposure time at risk for dapagliflozin initiators and comparators. Unadjusted incidence rate ratios (IRRs) of the outcome of interest with 95% confidence intervals in dapagliflozin users versus other AD users will be calculated, and adjusted using propensity score–stratified analysis. Analyses will be conducted in each data source separately, and a pooled estimate will be calculated if deemed appropriate.