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A Study Using Medical Records of Danish People With Type 2 Diabetes Comparing Empagliflozin and Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) in the Occurrence of Serious Cardiovascular Outcomes
Cardiovascular Outcomes, and Mortality in Danish Patients With Type 2 Diabetes Who Initiate Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA): A Danish Nationwide Comparative Effectiveness Study [EMPLACEtm]
Lead sponsor
Asset
Liraglutide
Subcutaneous · GLP-1 agonist
Listed sites
1
Recruiting sites
—
Enrollment
26,774
actual
Study population
Type 2 diabetes
Key I/E criterion
—
Primary endpoint
•Expanded / custom MACE composite (All-cause death, Non-fatal stroke, Non-fatal MI, Unstable angina hospitalization)
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Study population text
The source population for our study consists of individuals with type 2 diabetes, who are defined in our study as individuals who live in Denmark and who have never used oral antihyperglycemic drugs or insulin.
Inclusion criteria
The empagliflozin-exposed population must also meet the following criteria:
The population exposed to GLP1-RA must meet the following criteria:
Exclusion criteria
-Patients with type 1 diabetes T1D before the index date will not be included in the study.
Exclusion criteria by outcome of interest: Different exclusion criteria will be applied to generate sets of cohorts for the analysis of the different outcomes of interest.
In one main analysis, we will assess co-primary and secondary outcomes among all patients, regardless of a history of previous outcome events being present or not. In other words, we will allow a previous history of CVD events. We will adjust for the history of these events in the regression model rather than excluding patients with previous events (e.g. assess outcome rates of myocardial infarction in empagliflozine and liraglutide initiators while adjusting for previous history of myocardial infarction, unstable angina, or coronary revascularization).
In another main analysis of outcomes, we will exclude patients who had a specific outcome previously.
For example in the analysis of the primary heart failure outcome (heart failure admission or loop-diuretics), patients will not be included if a diagnosis of heart failure is recorded any time before or at the index date, or if a prescription for loop-diuretics has been filled within 12 months before or at the index date. For the secondary outcome of acute hospital admission with heart failure, we will include also patients with previous prescription for loop-diuretics, but exclude those with previous heart failure admission.
For analysis of stroke, patients will not be included if a diagnosis of stroke is recorded any time before or at the index date.
For analysis of myocardial infarction, unstable angina, or coronary revascularization, patients will not be included if any of these 3 major atherosclerotic cardiovascular events are recorded any time before or at the index date.
In additional analyses, other criteria will apply (To be discussed, RWT). Thus, an additional analysis will include also patients with previous outcome events, and adjust for the history of these events in the regression model rather than excluding them (e.g. assess outcome rates of myocardial infarction in empagliflozine and liraglutide initiators while adjusting for previous history of myocardial infarction, unstable angina, or coronary revascularization).
Endpoints (28)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Cardiovascular outcomes
20 endpointsIncidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsAll-cause death, Non-fatal stroke, Non-fatal MI, Unstable angina hospitalization, Coronary revascularization, Heart-failure hospitalization
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 36.1 | — |
| Liraglutide - PS Balanced Cohort | 35.9 | — |
Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsAll-cause death, Non-fatal stroke, Non-fatal MI, Unstable angina hospitalization, Coronary revascularization, Heart-failure hospitalization
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 39.9 | — |
| Liraglutide - PS Balanced Cohort | 37.3 | — |
Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
composite event, event
componentsAll-cause death, Non-fatal stroke, Non-fatal MI, Unstable angina hospitalization, Coronary revascularization, Heart-failure hospitalization
Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsAll-cause death, Non-fatal stroke, Non-fatal MI, Unstable angina hospitalization, Coronary revascularization, Heart-failure hospitalization
Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsHeart-failure hospitalization, All-cause death
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 21.1 | — |
| Liraglutide - PS Balanced Cohort | 22.2 | — |
Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsHeart-failure hospitalization, All-cause death
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 25.1 | — |
| Liraglutide - PS Balanced Cohort | 24.3 | — |
Incidence Rate of All-cause Hospitalization or Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsAll-cause hospitalization, All-cause death
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 193.5 | — |
| Liraglutide - PS Balanced Cohort | 212.1 | — |
Incidence Rate of All-cause Hospitalization or Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsAll-cause hospitalization, All-cause death
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 175.2 | — |
| Liraglutide - PS Balanced Cohort | 187.0 | — |
Incidence Rate of All Cause Hospitalization - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause hospitalization
event count, event
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 190.2 | — |
| Liraglutide - PS Balanced Cohort | 208.0 | — |
Incidence Rate of All Cause Hospitalization - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause hospitalization
event count, event
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 171.6 | — |
| Liraglutide - PS Balanced Cohort | 183.7 | — |
Incidence Rate of All-cause Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause death
event count, event
SNOMED 419620001
Posted result
| Group | Value (number), Events per 1000 patient-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 12.9 | — |
| Liraglutide - PS Balanced Cohort | 13.2 | — |
Incidence Rate of All-cause Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause death
event count, event
SNOMED 419620001
Posted result
| Group | Value (number), Events per 1000 patient-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 18.0 | — |
| Liraglutide - PS Balanced Cohort | 17.1 | — |
Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
event count, event
componentsHeart-failure hospitalization, All-cause death
Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
composite event, event
componentsHeart-failure hospitalization, All-cause death
Incidence Rate of All-cause Hospitalization or Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
composite event, event
componentsAll-cause hospitalization, All-cause death
Incidence Rate of All-cause Hospitalization or Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Expanded / custom MACE composite
composite event, event
componentsAll-cause hospitalization, All-cause death
Incidence Rate of All Cause Hospitalization - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause hospitalization
event count, event
Incidence Rate of All Cause Hospitalization - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause hospitalization
event count, event
Incidence Rate of All-cause Death - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause death
event count, event
SNOMED 419620001
Incidence Rate of All-cause Death - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
All-cause death
event count, event
SNOMED 419620001
Heart failure
8 endpointsIncidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure composite
event count, event
componentsHeart-failure hospitalization
SNOMED 84114007
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 12.9 | — |
| Liraglutide - PS Balanced Cohort | 18.0 | — |
Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure composite
event count, event
componentsHeart-failure hospitalization, Heart-failure hospitalization
SNOMED 84114007
Posted result
| Group | Value (number), Events per 1000 person-years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 17.7 | — |
| Liraglutide - PS Balanced Cohort | 21.4 | — |
Incidence Rate of Hospitalization for Heart Failure (HF) - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure hospitalization
event count, event
SNOMED 84114007
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 9.3 | — |
| Liraglutide - PS Balanced Cohort | 10.6 | — |
Incidence Rate of Hospitalization for Heart Failure (HF) - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure hospitalization
event count, event
SNOMED 84114007
Posted result
| Group | Value (number), Events per 1000 patient years | 95% CI |
|---|---|---|
| Empagliflozin - PS Balanced Cohort | 9.3 | — |
| Liraglutide - PS Balanced Cohort | 9.4 | — |
Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure composite
composite event, event
componentsHeart-failure hospitalization
SNOMED 84114007
Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure composite
composite event, event
componentsHeart-failure hospitalization
Incidence Rate of Hospitalization for Heart Failure (HF) - OT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure hospitalization
event count, event
SNOMED 84114007
Incidence Rate of Hospitalization for Heart Failure (HF) - ITT Analysis
Time frame:From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
Heart-failure hospitalization
event count, event
SNOMED 84114007
Publications (1)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- Diabetes therapy : research, treatment and education of diabetes and related disorders2022 Dec (month)PMID36315384doi:10.1007/s13300-022-01323-yvia clinicaltrials gov reference derived + pubmed nct search
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.