Cancer in Patients on Dapagliflozin and Other Antidiabetic Treatment

This is a multinational cohort database study to estimate the incidence of female breast
cancer and bladder cancer, by insulin use at cohort entry, 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 a large
populations.

The study will be implemented in four administrative health care data sources in three
countries: in the United Kingdom, the Clinical Practice Research Datalink (CPRD); in the
United States, the Centers for Medicare and Medicaid Services (CMS) Medicare databases and
the HealthCore Integrated Research Database (HIRDSM); and, in the Netherlands, the PHARMO
Database Network. Individuals in the databases will be included in the study if they meet the
following age criteria; 40 years or older (CPRD and PHARMO), 40 to 64 years (HIRD) or 65
years or older (Medicare); and if they did not have type 1 diabetes, were treated with 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 November 13, 2012 in CPRD,
November 1, 2013 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. patient was newly prescribed dapagliflozin or newly prescribed an AD (with or without
other ADs) in a class other than SGLT2 inhibitors, insulin monotherapy, metformin
monotherapy, or sulfonylurea monotherapy on the prescription index date

2. patient is aged 40 years or older at cohort entry; and

3. patient was enrolled in the data source for at least 180 days before the prescription
index date.

Exclusion Criteria:

1. any evidence of diagnosis of type 1 diabetes before cohort entry or use of insulin
alone as the first recorded AD;

2. any diagnosis of cancer before cohort entry (other than nonmelanoma skin cancer);

3. any recording of hematuria before cohort entry;

4. any cystoscopy or urine cytology performed before cohort entry;

5. any breast biopsy performed before cohort entry.