Status: Ongoing
First registered on:
04/06/2019
Last updated on:
03/03/2023
1. Study identification
EU PAS Register NumberEUPAS29985
Official titleCardiovascular and renal outcomes, and mortality in Danish patients with type 2 diabetes who initiate empagliflozin versus GLP1-RA: A Danish nationwide comparative effectiveness study
Study title acronymEMPLACE
Study typeOther: Cohort observational study
Brief description of the studyTo compare, among patients with type 2 diabetes in Denmark, clinical outcomes among new users (initiators) of empagliflozin versus GLP1-RA. Our primary objective is to compare clinical outcomes (cardiovascular and renal outcomes and mortality) among empagliflozin initiators versus liraglutide and other GLP1-RA initiators in Denmark. This is a non-interventional cohort study using existing data. The study will use a new user design and compare new users of empagliflozin with new users of GLP1-RA. The study population will include all eligible patients with type 2 diabetes initiating treatment with empagliflozin or with GLP1-RA between 2015 and until 2020 or the latest date of data availability.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research groupAarhus University, Dept of Clinical Epidemiology
Organisation/affiliationAarhus University / Aarhus University Hospital
Details of (Primary) lead investigator
Title Professor
Last name Sørensen
First name Henrik Toft
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
Denmark
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed05/12/201705/12/2017
Start date of data collection01/10/201801/10/2018
Start date of data analysis01/04/2019
Date of interim report, if expected
Date of final study report30/06/2023
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesBoehringer Ingelheim100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Thomsen
First name Reimar W
Address line 1Aarhus University, Dept of Clinical Epidemiology
Address line 2
Address line 3Olof Palmes Allé 43-45
CityAarhus N
Postcode8200
CountryDenmark
Phone number (incl. country code)45-87168403
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Thomsen
First name Reimar W
Address line 1Aarhus University, Dept of Clinical Epidemiology
Address line 2
Address line 3Olof Palmes Allé 43-45
CityAarhus N
Postcode8200
CountryDenmark
Phone number (incl. country code)45-87168403
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Multi-Constituent (Substance INN(s))EMPAGLIFLOZIN
LIRAGLUTIDE
GLP1-RA class
7. Medical conditions to be studied
Medical condition(s)Yes
Type 2 diabetes mellitus
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
Other population
Renal impaired
Hepatic impaired
Immunocompromised
Pregnant women
9. Number of subjects
Estimated total number of subjects50000
Additional information
In first analysis on cardiovascular and mortality outcomes, we were able to include 14,498 incident empagliflozin users and 12,706 incident liraglutide users (liraglutide was the overwhelmingly used (>95%) GLP-1RA in Denmark until 2018). Planned are 2 more study years up to 2020, which may yield apprx. 25,000 incident empagliflozin users and 25,000 incident GLP-1RA users.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Administrative database, e.g. claims database
Pharmacy dispensing records
Nationwide health care databases
11. Scope of the study
What is the scope of the study?
Disease epidemiology
Effectiveness evaluation
Primary scope : Effectiveness evaluation
12. Main objective(s)
What is the main objective of the study?
Our primary objective is to compare clinical outcomes (cardiovascular events, mortality) among empagliflozin initiators and liraglutide initiators in Denmark.
Are there primary outcomes?Yes
Primary outcome is a composite of hospitalization due to stroke, myocardial infarction, unstable angina, coronary revascularization, heart failure (HF), or all-cause death (expanded MACE).
Are there secondary outcomes?Yes
Secondary outcomes are first hospital admission with a diagnosis of HF and/or initiation of loop diuretics, hospital admission with HF and/or all-cause death, composite of all-cause hospitalization or death, all cause hospitalization, all-cause death, hospitalization for HF.
In additional analyses, we will assess total healthcare resources utilization and cost.
13. Study design
What is the design of the study?
Cohort study
Nationwide population-based comparative effectiveness cohort study based on prospective medical databases in Denmark
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
We compute incidence rates of outcomes per 1,000 person-years (pyrs) and use Cox regression to compute adjusted hazard ratios (aHRs). We apply propensity score balancing of potential confounders across the two treatment groups by inverse probability treatment weighting (IPTW), controlling age, gender, year of inclusion, diabetes duration, number of diabetes drugs used, metformin use, insulin use, diagnoses of retinopathy, neuropathy, or nephropathy, estimated glomerular filtration rate (eGFR), history of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, heart failure (further divided by duration and primary/secondary diagnosis), medical obesity, chronic obstructive pulmonary disease, cancer, use of angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs), other antihypertensives, statins, antiplatelet drugs, social and frailty markers, marital status, prescriptions for mental disorders, alcoholism, and prior admissions.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Thomsen RW, Knudsen JS, Kahlert J, Baggesen LM, Lajer M, Holmgaard PH, Vedin O, Ustyugova A, Sørensen HT. Cardiovascular Events, Acute Hospitalizations, and Mortality in Patients With Type 2 Diabetes Mellitus Who Initiate Empagliflozin Versus Liraglutide: A Comparative Effectiveness Study. J Am Heart Assoc. 2021 Jun;10(11):e019356.https://www.ahajournals.org/doi/10.1161/JAHA.120.019356?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Thomsen RW, Christensen LWB, Kahlert J, Knudsen JS, Ustyugova A, Sandgaard S, Holmgaard P, Ehlers LH, Sørensen HT. Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark. Diabetes Ther. 2022 Dec;13(11-12):1891-1906.https://link.springer.com/article/10.1007/s13300-022-01323-y
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
