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Trial · Observational

CompletedPhase not statedResults postedRegistry data

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

NCTNCT03993132 (opens ClinicalTrials.gov in a new tab)Other id1245-0194
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase not stated
Enrollment
26,774 participants (actual)
Sponsor
Boehringer Ingelheim · Industry
Design
Not stated
Countries
1 country

Denmark

Start
1 Oct 2018
Primary completion
16 Jun 2022
Completion
16 Jun 2022
First posted
20 Jun 2019
Last update posted
12 Feb 2024
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201820192020202120222023
  1. Ph –

    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

    NCT03993132

    1 Oct 2018 to 16 Jun 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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).

Interventions

  • EmpagliflozinDrug
  • LiraglutideDrug

Arms1

  • Other

    Patients with type 2 diabetes

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. 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.

    Registry description

    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.

  2. 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.

    Registry description

    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.

Secondary outcomes(12)

  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.

    Registry description

    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.

  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.

    Registry description

    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.

  3. 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.

    Registry description

    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.

  4. 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.

    Registry description

    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.

  5. 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.

    Registry description

    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.

  6. 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.

    Registry description

    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.

  7. 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.

    Registry description

    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.

  8. 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.

    Registry description

    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.

  9. 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.

    Registry description

    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.

  10. 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.

    Registry description

    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.

  11. 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.

    Registry description

    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.

  12. 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.

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 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 - OT Analysis

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort36.1
Liraglutide - PS Balanced Cohort35.9
Primary outcomeNumber· 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

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort39.9
Liraglutide - PS Balanced Cohort37.3
Secondary and other outcome results(6)
Secondary outcomeNumber· 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 - OT Analysis

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort21.1
Liraglutide - PS Balanced Cohort22.2
Secondary outcomeNumber· 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

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort25.1
Liraglutide - PS Balanced Cohort24.3
Secondary outcomeNumber· 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

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort12.9
Liraglutide - PS Balanced Cohort18.0
Secondary outcomeNumber· 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

GroupValue (Events per 1000 person-years)
Empagliflozin - PS Balanced Cohort17.7
Liraglutide - PS Balanced Cohort21.4
Secondary outcomeNumber· 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

GroupValue (Events per 1000 patient years)
Empagliflozin - PS Balanced Cohort193.5
Liraglutide - PS Balanced Cohort212.1
Secondary outcomeNumber· 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

GroupValue (Events per 1000 patient years)
Empagliflozin - PS Balanced Cohort175.2
Liraglutide - PS Balanced Cohort187.0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Empagliflozin - PS Balanced CohortAll eligible adult patients (\>18 years) with type 2 diabetes (T2D) initiating treatment with empagliflozin in Denmark between 2015 and 2018, who were included in danish population-based linked registries (Civil Registration System, Danish National Patient Register, National Database of Reimbursed Prescriptions, LABKA Database). Patients were followed-up through 2020. Propensity score (PS) balancing was applied to match new users of empagliflozin to new users of liraglutide.881 / 14,1480 / 00 / 0
Liraglutide - PS Balanced CohortAll eligible adult patients (\>18 years) with type 2 diabetes (T2D) initiating treatment with liraglutide in Denmark between 2015 to 2018, who were included in danish population-based linked registries (Civil Registration System, Danish National Patient Register, National Database of Reimbursed Prescriptions, LABKA Database). Patients were followed-up through 2020. Propensity score (PS) balancing was applied to match new users of empagliflozin to new users of liraglutide.765 / 12,6260 / 00 / 0

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedThomsen RW, Christensen LWB, Kahlert J, Knudsen JS, Ustyugova A, Sandgaard S, Holmgaard P, Ehlers LH, Sorensen 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. doi: 10.1007/s13300-022-01323-y. Epub 2022 Oct 31. PMID 36315384

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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).

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