Clinical trial NCT02695095: Acute Liver Injury in Patients on Dapagliflozin
Official title: Comparison of the Risk of Acute Liver Injury Between Patients With Type 2 Diabetes Exposed to Dapafliglozin and Those Exposed to Other Antidiabetic Treatments
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Liver Injury
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-03-01
Enrollment: 424091
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are new users of dapagliflozin or the eligible comaprator drugs that meet the inclusion criteria and none of teh exclusion criteria.

Comparator patients will be matched to the dapagliflozin patients by propensity score if access to all eligible comparator subjects is feasible.

Brief summary: 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 with those who are new users of antidiabetic drugs (ADs) in classes other than sodium-glucose cotransporter 2 (SGLT2) inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylurea monotherapy.

Detailed description: The overall goal of this research study is to estimate the risk of hospitalization for acute liver injury in patients who are prescribed dapagliflozin compared to patients prescribed other specific oral antidiabetic drugs. Dapagliflozin and other antidiabetic drugs are used to treat type 2 diabetes mellitus. Because of the mechanism of action for dapagliflozin and results from small safety monitoring studies, there is interest in further evaluating the safety of dapagliflozin in large populations.

The study will be implemented in three administrative health care data sources in two countries: in the United Kingdom, the Clinical Practice Research Datalink (CPRD); and in the United States, the Centers for Medicare and Medicaid Services (CMS) Medicare databases and the HealthCore Integrated Research Database (HIRDSM). Individuals in the databases will be included in the study if they meet the following age criteria; 18 years and older (CPRD and HIRD), or 65 years or older (Medicare); and if they did not have type 1 diabetes, are new users of one of the study drugs and meet the criteria of at least 180 days of electronic data before their first prescription of the study drug. The study period starts July 1, 2013 in CPRD, January 1, 2014 in PHARMO and January 9, 2014 in the United States data sources, and will end at the latest available data at each database at the time of analysis

Eligibility criteria: Inclusion Criteria:

1. receive newly prescribed dapagliflozin (with or without other ADs) or a newly prescribed AD (with or withoutother ADs) in a class other than SGLT2 inhibitors, insulin monotherapy, metformin monotherapy, or sulfonylureamonotherapy;
2. do not have evidence of type 1 diabetes;
3. are aged 18 years or older at the index date for CPRDpatients, 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:

* previous diagnosis of ALI; liver, biliary, or pancreatic disease; hepatobiliary or pancreatic neoplasm; or congestive heart failure

Primary outcomes:
measure: incidence of acute liver injury
timeFrame: Day after index day up to six years
Secondary outcomes:
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Research Site
state: Delaware
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: RTI Health Solutions
name: Catherine Johannes, Dr
role: PRINCIPAL_INVESTIGATOR
References: