Complications of UTI in Patients on Dapagliflozin

The overall goal of this research study is to estimate the sex-specific incidence of
hospitalization or emergency department visit for severe complications of urinary tract
infections, defined as pyelonephritis and urosepsis, 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

Inclusion Criteria:

1. 18 years and older (CPRD and HIRD), or 65 years or older (Medicare);

2. no diagnosisi of type 1 diabetes,

3. are new users of one of the study drugs and

4. have at least 180 days of electronic data before their first prescription of the study
drug

Exclusion Criteria:

1. The patient experienced chronic pyelonephritis at any time before the index date
(i.e., during the available lookback time).

2. The patient was prescribed an SGLT2 inhibitor other than dapagliflozin on or before
the index date.

3. The patient initiated metformin or sulfonylurea as AD monotherapy at the index date.

4. The patient initiated insulin therapy at the index date.

5. The patient had evidence of type 1 diabetes before cohort entry or first recorded AD
is insulin monotherapy