Empa PASS on Urinary Tract Malignancies

NCT03464045 | Completed Results

• 1 other identifier: 1245-0097
• Study Type: observational
• Target: 344,995
• Locations: 3 countries
• Sites: 3

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• Occurrence of Urinary Tract Cancer

  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.

  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

  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.

  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 Renal Cancer

  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.

  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).

Study Arms (6)

Empagliflozin initiators - UK

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).

Drug: empagliflozin

DPP4-i initiators - UK

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.

Drug: DPP-4 inhibitors

Empagliflozin initiators - Sweden

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.

Drug: empagliflozin

DPP4-i initiators - Sweden

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.

Drug: DPP-4 inhibitors

Empagliflozin initiators - Finland

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.

Drug: empagliflozin

DPP4-i initiators - Finland

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.

Drug: DPP-4 inhibitors

Interventions

empagliflozin DRUG

empagliflozin

Empagliflozin initiators - Finland; Empagliflozin initiators - Sweden; Empagliflozin initiators - UK

DPP-4 inhibitors DRUG

DPP-4 inhibitors

DPP4-i initiators - Finland; DPP4-i initiators - Sweden; DPP4-i initiators - UK

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This is an observational, comparative, cohort safety study based on European healthcare databases and includes databases from the UK, Finland, and Sweden.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (3)

The National Register Data

Helsinki, Finland

Location

The Swedish prescribed drug register

Stockholm, Sweden

Location

United Kingdom Clinical Practice Research Datalink (CPRD)

London, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Pasi Korhonen, 358-50-3652990

  pasi.korhonen@epidresearch.com

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 13, 2018
• Study Start: November 16, 2016
• Primary Completion: March 11, 2024
• Study Completion: March 11, 2024
• Last Updated: April 20, 2025
• Results First Posted: March 28, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); SE (1); GB (1)