Empa PASS on Urinary Tract Malignancies

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: empagliflozin; Drug: DPP-4 inhibitors

• Registration Number: NCT03464045
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The aim of the study is to assess the risk of urinary tract malignancies in patients initiating empagliflozin (free or fixed dose combination) compared to patients initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-16
• Study First Submitted: 2018-03-07
• Study First Submitted QC: 2018-03-07
• Study First Posted: 2018-03-13
• Primary Completion: 2024-03-11
• Study Completion: 2024-03-11
• Results First Submitted: 2025-03-10
• Results First Submitted QC: 2025-03-10
• Results First Posted: 2025-03-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 344995

Inclusion Criteria

• Diagnosis of type 2 diabetes
• Age over 18 years at index date
• At least 1 year of membership in the medication database prior to index date

Exclusion Criteria

• Patients with any cancer (excluding non-melanoma skin cancer) recorded at any time prior to the index date (i.e. during the available look-back time)
• Diagnosis of type 1 diabetes or other specific non-type 2 diabetes
• Use of any SGLT-2 inhibitor or any DPP-4 inhibitor (including free and fixed-dose combinations) recorded at any time prior to index date (i.e. during the available look-back time).
• Use of fixed-dose combinations of SGLT-2 inhibitors with DPP-4 inhibitors
• Diagnosis of end stage renal disease or receipt of renal dialysis recorded at any time prior to index date (i.e. during the available look-back time)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Empagliflozin initiators - UK	empagliflozin	Participants with Type 2 diabetes mellitus (T2D) initiating (first purchase/prescription) empagliflozin (study drug), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2021 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from Clinical Practice Research Datalink (CPRD) (General practitioner Online Data \[GOLD\], and Aurum) in the United Kingdom (UK).
DPP4-i initiators - UK	DPP-4 inhibitors	Participants with T2D initiating (first purchase/prescription) a dipeptidyl peptidase-4 inhibitor (DPP-4i) (comparator), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2021 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from CPRD (General practitioner Online Data \[GOLD\], and Aurum) in the UK.
Empagliflozin initiators - Sweden	empagliflozin	Participants with T2D initiating (first purchase/prescription) empagliflozin (study drug), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2020 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from the nationwide registers in Sweden.
DPP4-i initiators - Sweden	DPP-4 inhibitors	Participants with T2D initiating (first purchase/prescription) a dipeptidyl peptidase-4 inhibitor (DPP-4i) (comparator), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2020 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from the nationwide registers in Sweden.
DPP4-i initiators - Finland	DPP-4 inhibitors	Participants with T2D initiating (first purchase/prescription) a dipeptidyl peptidase-4 inhibitor (DPP-4i) (comparator), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2020 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from the nationwide registers in Finland.
Empagliflozin initiators - Finland	empagliflozin	Participants with T2D initiating (first purchase/prescription) empagliflozin (study drug), in free form or in fixed-dose combination with metformin, between 1-Aug-2014 and 31-Dec-2020 (index date), and with more than 6 months of possible follow-up (index date less than 6 months prior to end of study date). The study population was identified from the nationwide registers in Finland.

Primary Outcome Measures

Name	Time	Method
Occurrence of Urinary Tract Cancer	From 181 days after index date until the occurrence of a censoring event or cancer outcome event. Up to 6 (Sweden/Finland) or 7 years (UK).	Occurrence of urinary tract cancer, which include malignant neoplasm and carcinoma in situ of the urinary tract, is reported as incidence rates per 1000 patient years. Incidence rates were estimated using Poisson regression and computed as the number of outcome events divided by the total person-time-at-risk (in years), multiplied by 1,000 for easier comparison. The country-level datasets were analyzed separately. Thereafter, pooled incidence rates were estimated using the aggregated number of outcome events and time-at-risk of all study countries using the Poisson regression.
Occurrence of Bladder Cancer	From 181 days after index date until the occurrence of a censoring event or cancer outcome event. Up to 6 (Sweden/Finland) or 7 years (UK).	Occurrence of bladder cancer, malignant and carcinoma in situ, is reported as incidence rates per 1000 patient years. Incidence rates were estimated using Poisson regression and computed as the number of outcome events divided by the total person-time-at-risk (in years), multiplied by 1,000 for easier comparison. The country-level datasets were analyzed separately. Thereafter, pooled incidence rates were estimated using the aggregated number of outcome events and time-at-risk of all study countries using the Poisson regression.
Occurrence of Renal Cancer	From 181 days after index date until the occurrence of a censoring event or cancer outcome event. Up to 6 (Sweden/Finland) or 7 years (UK).	Occurrence of malignant renal cancer is reported as incidence rates per 1000 patient years. Incidence rates were estimated using Poisson regression and computed as the number of outcome events divided by the total person-time-at-risk (in years), multiplied by 1,000 for easier comparison. The country-level datasets were analyzed separately. Thereafter, pooled incidence rates were estimated using the aggregated number of outcome events and time-at-risk of all study countries using the Poisson regression.

Trial Locations

Locations (3)

United Kingdom Clinical Practice Research Datalink (CPRD); 🇬🇧 London, United Kingdom

The Swedish prescribed drug register; 🇸🇪 Stockholm, Sweden

The National Register Data; 🇫🇮 Helsinki, Finland