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

Adults (18 to < 46 years)
Adults (46 to < 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.
Documents
Study results

0304030_Dapa ALI Final Report_Final_9Nov2020_Abstract_Redacted

English (185.54 KB - PDF)View document
Study publications
Danysh HE, Johannes CB, Beachler DC, Layton JB, Ziemiecki R, Arana A, Dinh J, L…
Johannes C, Layton JB, Beachler DC, Ziemiecki RM, Li L, Danysh HE, Dinh J, Hunt…
Johannes C, Beachler D, Ziemiecki R, Yin R, McGrath L, Jemison J, Lanes S, Gils…
Layton JB, Zhou CK, Danysh HE, Beachler DC, Ziemiecki R, Dinh J, Yin R, Calinga…