Ignite Creation Date:
2025-12-24 @ 9:44 PM
Ignite Modification Date:
2026-01-01 @ 10:53 AM
Study NCT ID:
NCT03993132
Status:
COMPLETED
Last Update Posted:
2024-02-12
First Post:
2019-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
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
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C570240', 'term': 'empagliflozin'}, {'id': 'D000069450', 'term': 'Liraglutide'}], 'ancestors': [{'id': 'D052216', 'term': 'Glucagon-Like Peptide 1'}, {'id': 'D004763', 'term': 'Glucagon-Like Peptides'}, {'id': 'D052336', 'term': 'Proglucagon'}, {'id': 'D005768', 'term': 'Gastrointestinal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clintriage.rdg@boehringer-ingelheim.com', 'phone': '18002430127', 'title': 'Boehringer Ingelheim Call Center', 'organization': 'Boehringer Ingelheim'}, 'certainAgreement': {'otherDetails': "Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results.\n\nInvestigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days.\n\nBI may request a delay of the publication in order to protect BI's intellectual property rights.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'Due to a huge shift after 2018 in drug type use within the GLP-1RA group the final analysis (between 2015 - 2020) was not completed. Instead, an exploratory analysis was performed, using the initial analysis of comparing from empagliflozin versus liraglutide from 2015 to 2018 but following these same patients up to 2020.'}}, 'adverseEventsModule': {'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'This is a non-interventional study using electronic health care records, with data retrieved from Danish National Patient Registry, Danish National Prescription Registry and Danish Register of Causes of Death. No adverse events were collected on an individual case level. "0" in the Serious Adverse Events, and Other Adverse Events parts refer to not applicable.\n\nAll-cause death for ITT analysis is reported.', 'eventGroups': [{'id': 'EG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 14148, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 881, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 12626, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 765, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '36.1', 'groupId': 'OG000'}, {'value': '35.9', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.01', 'ciLowerLimit': '0.91', 'ciUpperLimit': '1.11', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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).\n\nThe 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.\n\nIn 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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'PRIMARY', 'title': 'Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '39.9', 'groupId': 'OG000'}, {'value': '37.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.07', 'ciLowerLimit': '1.01', 'ciUpperLimit': '1.13', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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).\n\nThe 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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '21.1', 'groupId': 'OG000'}, {'value': '22.2', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.95', 'ciLowerLimit': '0.84', 'ciUpperLimit': '1.08', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'The incidence rate of heart failure (HF) hospitalization or all-cause death based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '25.1', 'groupId': 'OG000'}, {'value': '24.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.03', 'ciLowerLimit': '0.96', 'ciUpperLimit': '1.11', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.9', 'groupId': 'OG000'}, {'value': '18.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.71', 'ciLowerLimit': '0.61', 'ciUpperLimit': '0.83', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.\n\nFor 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.\n\nIn 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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '17.7', 'groupId': 'OG000'}, {'value': '21.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.83', 'ciLowerLimit': '0.76', 'ciUpperLimit': '0.91', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.', 'unitOfMeasure': 'Events per 1000 person-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All-cause Hospitalization or Death - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '193.5', 'groupId': 'OG000'}, {'value': '212.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.92', 'ciLowerLimit': '0.88', 'ciUpperLimit': '0.96', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause hospitalization or death, based on on-treatment (OT) analysis is reported.\n\nFor 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All-cause Hospitalization or Death - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '175.2', 'groupId': 'OG000'}, {'value': '187.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.94', 'ciLowerLimit': '0.91', 'ciUpperLimit': '0.96', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause hospitalization or death, based on intent-to-treat (ITT) analysis.\n\nFor 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All Cause Hospitalization - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '190.2', 'groupId': 'OG000'}, {'value': '208.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.92', 'ciLowerLimit': '0.88', 'ciUpperLimit': '0.96', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all cause hospitalization, based on on-treatment (OT) analysis is reported.\n\nFor 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All Cause Hospitalization - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '171.6', 'groupId': 'OG000'}, {'value': '183.7', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.93', 'ciLowerLimit': '0.91', 'ciUpperLimit': '0.96', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all cause hospitalization, based on intent-to-treat (ITT) analysis.\n\nFor 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All-cause Death - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.9', 'groupId': 'OG000'}, {'value': '13.2', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.99', 'ciLowerLimit': '0.83', 'ciUpperLimit': '1.18', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause death, based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.', 'unitOfMeasure': 'Events per 1000 patient-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of All-cause Death - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '18.0', 'groupId': 'OG000'}, {'value': '17.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.06', 'ciLowerLimit': '0.97', 'ciUpperLimit': '1.16', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.', 'unitOfMeasure': 'Events per 1000 patient-years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of Hospitalization for Heart Failure (HF) - OT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '9.3', 'groupId': 'OG000'}, {'value': '10.6', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.87', 'ciLowerLimit': '0.72', 'ciUpperLimit': '1.06', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of hospitalization for heart failure (HF), based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}, {'type': 'SECONDARY', 'title': 'Incidence Rate of Hospitalization for Heart Failure (HF) - ITT Analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'OG000'}, {'value': '12626', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'OG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'classes': [{'categories': [{'measurements': [{'value': '9.3', 'groupId': 'OG000'}, {'value': '9.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.98', 'ciLowerLimit': '0.88', 'ciUpperLimit': '1.10', 'estimateComment': 'Hazard ratio compares empagliflozin versus liraglutide (reference).', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'A Cox regression with selected variables based on previous literature, covariate data availability, examination of exposure group differences in the distribution of each covariate, and the association of covariates with the outcomes of interest was applied. The hazard ratio compare Empagliflozin versus Liraglutide (reference).'}], 'paramType': 'NUMBER', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of hospitalization for heart failure (HF), based on intent-to-treat (ITT) analysis.\n\nFor 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.', 'unitOfMeasure': 'Events per 1000 patient years', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'FG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'comment': 'Propensity score balanced cohort', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14148'}, {'groupId': 'FG001', 'numSubjects': '12626'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14148'}, {'groupId': 'FG001', 'numSubjects': '12626'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'This non-interventional cohort study based on existing data planned to compare new users of empagliflozin with new users of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) in Denmark between 21015 and 2020. Due to a huge shift after 2018 in drug type use within the GLP-1RA group the final analysis was not completed.', 'preAssignmentDetails': 'All subjects were screened for eligibility to ensure that they (the subjects) strictly met all inclusion and none of the exclusion criteria.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'BG000'}, {'value': '12626', 'groupId': 'BG001'}, {'value': '26774', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Empagliflozin - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'BG001', 'title': 'Liraglutide - PS Balanced Cohort', 'description': 'All 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.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'BG000'}, {'value': '12626', 'groupId': 'BG001'}, {'value': '26774', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '61.55', 'groupId': 'BG000', 'lowerLimit': '52.73', 'upperLimit': '69.83'}, {'value': '61.19', 'groupId': 'BG001', 'lowerLimit': '52.31', 'upperLimit': '69.83'}, {'value': '61.37', 'groupId': 'BG002', 'lowerLimit': '52.54', 'upperLimit': '69.70'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'Years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '14148', 'groupId': 'BG000'}, {'value': '12626', 'groupId': 'BG001'}, {'value': '26774', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '5692', 'groupId': 'BG000'}, {'value': '5162', 'groupId': 'BG001'}, {'value': '10854', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '8456', 'groupId': 'BG000'}, {'value': '7464', 'groupId': 'BG001'}, {'value': '15920', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}], 'populationDescription': 'All patients included in the propensity score (PS) balanced cohort of either empagliflozin or liraglutide users.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-11-08', 'size': 3478156, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-06-14T06:59', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26774}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-10-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-06', 'completionDateStruct': {'date': '2022-06-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-06-15', 'studyFirstSubmitDate': '2019-06-19', 'resultsFirstSubmitDate': '2023-06-15', 'studyFirstSubmitQcDate': '2019-06-19', 'lastUpdatePostDateStruct': {'date': '2024-02-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-06-15', 'studyFirstPostDateStruct': {'date': '2019-06-20', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-02-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-06-16', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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).\n\nThe 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.\n\nIn 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.'}, {'measure': 'Incidence Rate of Expanded Major Adverse Cardiovascular Event (MACE) Composite Outcome - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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).\n\nThe 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.'}], 'secondaryOutcomes': [{'measure': 'Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'The incidence rate of heart failure (HF) hospitalization or all-cause death based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.'}, {'measure': 'Incidence Rate of Heart Failure (HF) Hospitalization or All-cause Death - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.'}, {'measure': 'Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.\n\nFor 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.\n\nIn 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.'}, {'measure': 'Incidence Rate of First Hospitalized Heart Failure (HHF) or Initiation of Community Prescription Drug Therapy With Loop Diuretics - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.'}, {'measure': 'Incidence Rate of All-cause Hospitalization or Death - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause hospitalization or death, based on on-treatment (OT) analysis is reported.\n\nFor 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.'}, {'measure': 'Incidence Rate of All-cause Hospitalization or Death - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause hospitalization or death, based on intent-to-treat (ITT) analysis.\n\nFor 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.'}, {'measure': 'Incidence Rate of All Cause Hospitalization - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all cause hospitalization, based on on-treatment (OT) analysis is reported.\n\nFor 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.'}, {'measure': 'Incidence Rate of All Cause Hospitalization - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all cause hospitalization, based on intent-to-treat (ITT) analysis.\n\nFor 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.'}, {'measure': 'Incidence Rate of All-cause Death - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of all-cause death, based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.'}, {'measure': 'Incidence Rate of All-cause Death - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', '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.'}, {'measure': 'Incidence Rate of Hospitalization for Heart Failure (HF) - OT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of hospitalization for heart failure (HF), based on on-treatment (OT) analysis is reported.\n\nFor 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.\n\nIn 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.'}, {'measure': 'Incidence Rate of Hospitalization for Heart Failure (HF) - ITT Analysis', 'timeFrame': 'From first initiation of empagliflozin or liraglutide until end of follow-up, up to 6 years.', 'description': 'Incidence rate of hospitalization for heart failure (HF), based on intent-to-treat (ITT) analysis.\n\nFor 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.'}]}, 'conditionsModule': {'conditions': ['Diabetes Mellitus, Type 2']}, 'referencesModule': {'references': [{'pmid': '36315384', 'type': 'DERIVED', 'citation': 'Thomsen 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.'}], 'seeAlsoLinks': [{'url': 'https://www.mystudywindow.com', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': '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).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nThe empagliflozin-exposed population must also meet the following criteria:\n\n* 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\n* Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date\n* Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date\n\nThe population exposed to GLP1-RA must meet the following criteria:\n\n* 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.\n* Have no prescription/dispensing of a GLP-1 receptor agonist alone or in fixed dose combination prior to the index date\n* Have no prescription/dispensing of SGLT2 inhibitors (including empagliflozin) alone or in fixed-dose combination prior to the index date\n\nExclusion Criteria:\n\n-Patients with type 1 diabetes T1D before the index date will not be included in the study.\n\nExclusion 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.\n\nIn 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).\n\nIn another main analysis of outcomes, we will exclude patients who had a specific outcome previously.\n\nFor 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.\n\nFor analysis of stroke, patients will not be included if a diagnosis of stroke is recorded any time before or at the index date.\n\nFor 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.\n\nIn 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).'}, 'identificationModule': {'nctId': 'NCT03993132', 'briefTitle': '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', 'organization': {'class': 'INDUSTRY', 'fullName': 'Boehringer Ingelheim'}, 'officialTitle': '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]', 'orgStudyIdInfo': {'id': '1245-0194'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patients with type 2 diabetes', 'interventionNames': ['Drug: Empagliflozin', 'Drug: Liraglutide']}], 'interventions': [{'name': 'Empagliflozin', 'type': 'DRUG', 'description': 'new users (initiators) of Empagliflozin', 'armGroupLabels': ['Patients with type 2 diabetes']}, {'name': 'Liraglutide', 'type': 'DRUG', 'description': 'initiators of Liraglutide', 'armGroupLabels': ['Patients with type 2 diabetes']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8200', 'city': 'Aarhus', 'country': 'Denmark', 'facility': 'Department of Clinical Epidemiology - Aarhus Unversiteteshospital', 'geoPoint': {'lat': 56.15674, 'lon': 10.21076}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', '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).\n\nFor more details refer to: https://www.mystudywindow.com/msw/datatransparency'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}