Comparison of the risk of acute outcomes between patients with type 2 diabetes exposed to dapagliflozin and those exposed to other antidiabetic treatments

Date of Approval: 
2015-12-21 00:00:00
Lay Summary: 
The overall goal of this research study is to estimate the risk of hospitalization for acute kidney injury (AKI), hospitalization for acute liver injury (ALI), and severe complications of urinary tract infections (UTI) in patients who are prescribed dapagliflozin compared to patients prescribed other oral antidiabetic drugs (ADs). Dapagliflozin and other antidiabetic drugs are used to treat type 2 diabetes mellitus. Because of the way dapagliflozin works in the body, there is interest in further evaluating its safety in a large population. 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 (HIRD). 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). The final study report will be submitted for review to the European Medicines Agency to ensure the continued safety of the drug and will be submitted for publication in a scientific journal.
Technical Summary: 
This cohort study compares the incidences of hospitalization for AKI, hospitalization for ALI, and sex-specific incidence of severe complications of UTI among new users of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor medication, with those among new users of other specific ADs. The study duration is 5 years. Follow-up will start on the date a patient has a first prescription recorded in CPRD or dispensing recorded in the other data sources for a study drug, and will continue until first occurrence of any acute end-point, death, discontinuation from the study database, or the end of the study. The study will be implemented in adults in three administrative health care data sources in two countries: United Kingdom: the Clinical Practice Research Datalink; and the United States: the Centers for Medicare and Medicaid Services Medicare databases and the HealthCore Integrated Research Database. Propensity scores will be estimated at cohort entry by logistic regression models. Incidence rates of each outcome will be determined in each cohort. Propensity score stratification will be used to estimate adjusted incidence rate ratios comparing dapagliflozin with comparator ADs for each outcome of interest with 95% confidence intervals. Analyses will be conducted in each data source, and a pooled estimate will be calculated using aggregate data, if deemed appropriate.
Application Number: 

Kay Johannes - Chief Investigator - RTI Health Solutions
Leah McGrath - Corresponding Applicant - RTI Health Solutions
Alejandro Arana Navarro - Collaborator - RTI Health Solutions
Alicia Gilsenan - Collaborator - RTI Health Solutions
Brian Calingaert - Collaborator - RTI Health Solutions
David Martinez - Collaborator - RTI Health Solutions
Elizabeth Andrews - Collaborator - RTI Health Solutions
Estel Plana Hortoneda - Collaborator - RTI Health Solutions
Heather Danysh - Collaborator - RTI Health Solutions
J. Bradley Layton - Collaborator - RTI Health Solutions
Jaume Aguado - Collaborator - RTI Health Solutions
Jennifer Bartsch - Collaborator - RTI Health Solutions
Joan Fortuny - Collaborator - RTI Health Solutions
Jordi Castellsague - Collaborator - RTI Health Solutions
Karolina Andersson Sundell - Collaborator - Astra Zeneca R&D Molndal Sweden
Lia Gutierrez - Collaborator - RTI Health Solutions
Lisa McQuay - Collaborator - RTI Health Solutions
MANEL PLADEVALL - Collaborator - RTI Health Solutions
Maria Reynolds - Collaborator - RTI Health Solutions
Ryan Ziemiecki - Collaborator - RTI Health Solutions
Shannon Hunter - Collaborator - RTI Health Solutions
Sophie Shen - Collaborator - Bristol-Myers Squibb Pharmaceuticals Limited - UK ( BMS )
Zhou Xiaolei - Collaborator - RTI Health Solutions

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