Acute Liver Injury in Patients on Dapagliflozin

Completed

• Conditions: Acute Liver Injury

• Registration Number: NCT02695095
• Lead Sponsor: AstraZeneca

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

Study Timeline

• Study First Submitted: 2016-02-18
• Study First Submitted QC: 2016-02-24
• Study First Posted: 2016-03-01
• Study Start: 2017-01-01
• Primary Completion: 2020-09-01
• Study Completion: 2020-11-30
• Status Verified: 2021-11
• Last Update Submitted: 2021-12-01
• Last Update Posted: 2021-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 424091

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
incidence of acute liver injury	Day after index day up to six years	Patients will be followed from their index date (date of first study drug prescription or dispensing) until they experience one of the following: an event under study, end of time at risk for index medication, death, addition of a non-dapagliflozin (up to six years)

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom