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

June 15, 2023 updated by: Boehringer Ingelheim

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]

The primary research question is to evaluate whether, among patients with type 2 diabetes mellitus (T2D), initiation of empagliflozin changes the adjusted incidence of outcomes compared with initiation of Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26774

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8200
        • Department of Clinical Epidemiology - Aarhus Unversiteteshospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

The empagliflozin-exposed population must also meet the following criteria:

  • Have at least one prescription for empagliflozin or fixed-dose combination of empagliflozin with another drug, with or without treatment with another glucose-lowering drug
  • Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date
  • Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date

The population exposed to GLP1-RA must meet the following criteria:

  • Have at least one prescription for GLP1-RA or a fixed-dose combination of GLP1-RA with another drug, with or without treatment with another glucose-lowering drug.
  • Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date
  • Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients with type 2 diabetes
Drug: Empagliflozin
new users (initiators) of Empagliflozin
Drug: Liraglutide
initiators of Liraglutide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.

Composite outcome includes: All-cause death, acute admission with non-fatal (within 30 days) stroke, with non-fatal (within 30 days) myocardial infarction (MI), admission with unstable angina, coronary revascularization, or acute admission with non-fatal heart failure (HF).

The results from on-treatment (OT) analysis are reported. For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added.

In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Composite outcome includes: All-cause death, acute admission with non-fatal (within 30 days) stroke, with non-fatal (within 30 days) myocardial infarction (MI), admission with unstable angina, coronary revascularization, or acute admission with non-fatal heart failure (HF).

The results from intention-to-treat (ITT) analysis are reported. For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.

The incidence rate of heart failure (HF) hospitalization or all-cause death based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added.

In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.
The incidence rate of heart failure (HF) hospitalization or all-cause death based on Intention-to-treat (ITT) analysis is reported. For the ITT analyses, participants are defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

The incidence rate of first hospitalized Heart Failure (HHF) or initiation of community prescription drug therapy with loop diuretics based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added.

In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.
The incidence rate of first hospitalized Heart Failure (HHF) or initiation of community prescription drug therapy with loop diuretics based on intention-to-treat (ITT) analysis was reported. For the ITT analyses, participants are defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of all-cause hospitalization or death, based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added. In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of all-cause hospitalization or death, based on intent-to-treat (ITT) analysis.

For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of all cause hospitalization, based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added. In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of all cause hospitalization, based on intent-to-treat (ITT) analysis.

For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of all-cause death, based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added.

In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.
Incidence rate of all-cause death, based on intent-to-treat (ITT) analysis. For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of hospitalization for heart failure (HF), based on on-treatment (OT) analysis is reported.

For the OT analyses, treatment duration was based on the estimated number of days covered by each filled prescription, calculated as the number of drug packages times the numerical volume of a package. A grace period of 30 days were added.

In the OT analysis, participants were censored from further follow-up at either treatment cessation, initiation of an alternative drug in the study drug class and initiation of a drug from the comparator study drug class.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.
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.

Incidence rate of hospitalization for heart failure (HF), based on intent-to-treat (ITT) analysis.

For the ITT analyses, participants were defined as exposed from the start of treatment throughout follow-up, analogous to an ITT design in a interventional trial. Follow-up was not censored if glucose-lowering drugs other than the index drugs were prescribed in addition to empagliflozin or GLP-1RA after the index date.
From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 16, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 16, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 20, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 12, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1245-0194

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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