Empagliflozin is a new medicine to treat type 2 diabetes (T2D) in adults. Kidney cancer is considered as a potential risk associated with the use of empagliflozin, based on animal studies and cases of bladder cancer seen in patient using drugs similar to empagliflozin. As part of monitoring the safety of empagliflozin, Boehringer Ingelheim International GmbH (BI) has committed to conduct a study of urinary tract cancers. Patients who are prescribed empagliflozin will be compared with otherwise similar patients who have used other medications to treat diabetes to see whether or not patients prescribed empagliflozin are more likely to have urinary tract cancers. The study will be conducted in the United Kingdom (UK), Sweden, and Finland using routinely collected health information. Anonymised patient level data from the UK, Sweden, and Finland will be combined to provide evidence on the risk of urinary tract cancer. Understanding of the treatment’s safety is important to all individuals using empagliflozin and also benefits individuals with T2D in England and Wales.
The aim of the study is to assess, in T2D, the risk of urinary tract malignancies in adult (over 18 years) patients initiating empagliflozin (free or fixed-dose combination) compared to patients initiating dipeptidyl peptidase-4 inhibitors (DPP-4i). This is an observational, comparative, cohort safety study based on healthcare databases in the UK, Sweden, and Finland. The primary outcomes are urinary tract cancers, bladder cancer, and renal cancer. CPRD GOLD and Aurum data will be used to define exposure, investigate outcomes, as well as define treatment and comorbidity history. In this “incident user” design study, new users of empagliflozin will be compared to the new users of DPP-4i. The incident users will be included in the period 2014-2021 and followed until the end of 2021, or the end of database follow-up, whichever occurs first. Empagliflozin initiators will be matched with DPP-4i initiators with similar treatment and clinical history at index date (study drug initiation date) using propensity scores (PS). Crude and adjusted incidence rates and their 95% confidence intervals (CIs) will be presented for the matched exposure cohorts. Crude and adjusted hazard ratios and 95% CIs will be estimated using Coxproportional hazard models , including time-varying covariates in the fully adjusted models. This post-authorisation safety study of empagliflozin benefits the potential users of this medication, including individuals with T2D living in England and Wales.
The three primary outcomes of the study are*: urinary tract cancers (malignant neoplasms of kidney, renal pelvis, ureter, bladder, or other unspecified urinary organs; and carcinoma in situ of bladder, or other unspecified urinary organs); bladder cancer; and renal cancer.
Secondary outcomes of the study are other urinary tract cancers**: other urinary tract cancers (non-renal, non-bladder cancers) including ureteral and urethral cancers; neoplasms of uncertain or unknown behaviour (includes non-malignant and excludes carcinomas in situ) of the urinary tract.
*In the main analysis, these outcomes will be identified from CPRD GOLD and Aurum data using the appropriate diagnostic codes for each data source (included in Appendix 2). Given the low proportion of practices eligible for linkage in CPRD GOLD (~44%) and to maximize sample size, HES data will not be used for the main analysis. In a sensitivity analysis, additional HES linked datasets (Outpatient care and Admitted Patient Care) will be used for primary outcomes identification using ICD-10 diagnostic codes (included in Appendix 2), if linked data with sufficient sample size during the study period will be available (~44% of CPRD GOLD (https://cprd.com/cprd-gold-october-2022-dataset) and ~91% CPRD Aurum (https://cprd.com/cprd-aurum-october-2022-dataset) practices take part in the linkage program).
**These outcomes will be identified from CPRD GOLD and Aurum data using the appropriate diagnostic codes for each data source
Soulmaz Fazeli Farsani - Chief Investigator - Boehringer-Ingelheim International GmbH
Vikrant Singh - Corresponding Applicant - IQVIA ( IMS Health ) France
Aaro Salosensaari - Collaborator - IQVIA Finland Oy
Anouk Deruaz Luyet - Collaborator - Boehringer-Ingelheim International GmbH
Fabian Hoti - Collaborator - IQVIA Finland Oy
Giorgi Tskhvarashvili - Collaborator - StatFinn Estonia OU
Hanna Rinta-Kokko - Collaborator - IQVIA Finland Oy
Jessie Oyinlola - Collaborator - CPRD
Josephine Dufitinema - Collaborator - IQVIA Finland Oy
Julia Pietilä - Collaborator - IQVIA Finland Oy
Kaia Aher - Collaborator - StatFinn Estonia OU
Kristin Avans - Collaborator - StatFinn Estonia OU
Muriel Lobier - Collaborator - IQVIA Finland Oy
Paula-Karoliina Põld - Collaborator - StatFinn Estonia OU
Pia Vattulainen - Collaborator - IQVIA Finland Oy
Rejane Fiqueiredo - Collaborator - IQVIA Finland Oy
Riho Klement - Collaborator - StatFinn Estonia OU
Rownak Jahan Archie - Collaborator - IQVIA Solutions Sweden AB
Sonia Guleria - Collaborator - IQVIA Solutions Sweden AB
Thi Ngoc Mai Nguyen - Collaborator - Boehringer-Ingelheim International GmbH
Thomas Faux - Collaborator - IQVIA Finland Oy
Vasili Mushnikov - Collaborator - IQVIA Finland Oy
Xu Qiao - Collaborator - IQVIA Finland Oy
Eric Beohou - Collaborator - IQVIA Solutions Sweden AB
Inger-Helen Maadik - Collaborator - StatFinn Estonia OU
Thi Ngoc Mai Nguyen - Collaborator - Boehringer-Ingelheim International GmbH
HES Admitted Patient Care;HES Outpatient;Practice Level Index of Multiple Deprivation