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

Study Overview
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Brief Summary
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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).

Official Title
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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]

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with type 2 diabetes<br> | Drug: Empagliflozin<br>* new users (initiators) of Empagliflozin<br>Drug: Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA)<br>* initiators of Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded Major Adverse Cardiovascular Event (MACE) composite outcome | 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) | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inpatient hospital admission with a diagnosis of heart failure (HF) and/or initiation of community prescription drug therapy with loop diuretics |  | Up to 3 years | 
| Inpatient hospital admission with a diagnosis of heart failure (HF) and/or all-cause death |  | Up to 3 years | 
| Composite of all-cause hospitalization or death |  | Up to 3 years | 
| All cause hospitalization |  | Up to 3 years | 
| All-cause death |  | Up to 3 years | 
| Hospitalization for heart failure (HF) |  | Up to 3 years |