Comparative Effectiveness of Empagliflozin in the US

Study Overview
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Brief Summary
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Empagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor, was launched as a treatment for type 2 diabetes mellitus (T2DM) in the U.S. in August 2014. In contrast with several previous cardiovascular outcomes trials, which failed to demonstrate an association with a higher or a lower risk of cardiovascular outcomes associated with members of other recently marketed antidiabetic classes, the EMPA-REG OUTCOME trial has shown that patients at high cardiovascular risk randomized to empagliflozin vs. placebo, were associated with a reduced risk of hospitalization for heart failure, cardiovascular mortality, and all-cause mortality. However, these and other findings arising from an extensive clinical trial program aimed at evaluating the efficacy and safety profile for empagliflozin have yet to be demonstrated in a non-trial environment. This study aims to investigate the transferability of the effects demonstrated in dedicated randomized clinical studies to a broader population under real world conditions.

Official Title
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EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Study Program

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: DPP-4 inhibitor
* Drug: GLP-1 receptor agonist


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients >= 18 years old for Marketscan and Optum, and >=65 years old for Medicare only Patients initiating empagliflozin or a DPP-4 inhibitor within the study period. Initiation was defined as no use of SGLT-2 inhibitors (canagliflozin, dapagliflozin, ertugliflozin) or DPP-4 inhibitors in the previous 12 months. Restriction to patients with a diagnosis of T2DM (ICD-9 Dx code of 250.x0 or 250.x2; ICD-10 Dx code of E11.x) in the 12 months prior to drug initiation. Exclusion criteria: Patients with missing or ambiguous age or sex information. All patients who have less than 12 months of continuous registration in the database prior to initiation of empagliflozin or a DPP-4 inhibitor will be excluded. Patients with type 1 diabetes mellitus (T1DM) defined as at least 1 inpatient or outpatient codes in the 12 months prior to drug initiation. Secondary diabetes, and gestational diabetes in the 12 months prior to drug initiation History of cancer in the 5 years prior to drug initiation End-stage renal disease (ESRD) in the 12 months prior to drug initiation HIV diagnosis or treatment in the 12 months prior to drug initiation Organ transplant in the 12 months prior to drug initiation Patients that were in nursing homes in the 12 months prior to drug initiation Patients with concomitant SGLT-2 inhibitor and DPP-4 inhibitor initiation will also be excluded. Patients initiating more than one DPP-4i on cohort entry date will additionally be excluded Additional exclusion criteria apply.

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 T2DM initiating empagliflozin<br>Type 2 diabetes mellitus | Drug: Empagliflozin<br>* Empagliflozin<br>* Other names: JARDIANCE, JARDIANZ, GIBTULIO;|
| patients with T2DM initiating a DPP-4 inhibitor<br>dipeptidyl peptidase-4 inhibitor treated patients | Drug: DPP-4 inhibitor<br>* dipeptidyl peptidase-4 inhibitor<br>|
| patients with T2DM initiating a GLP-1 receptor agonist<br>Glucagon-like peptide-1 receptor agonist treated patients | Drug: GLP-1 receptor agonist<br>* Glucagon-like peptide-1 receptor agonist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-point major adverse cardiovascular events (MACE) | i.e., non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular (CV) mortality; as well as each individual component: Hospital admission for MI (for purposes of this individual component, fatal MI is included) Hospital admission for stroke (for purposes of this individual component, fatal stroke is included) CV mortality | 60 months | 
| Hospitalization for heart failure (specific, based on primary inpatient diagnosis code) |  | 60 months | 
| Hospitalization for heart failure (broad, based on any inpatient diagnosis code) |  | 60 months | 
| Modified MACE | i.e., composite of MI, stroke or all-cause mortality | 60 months | 
| Composite of MI or stroke hospital admission for heart failure |  | 60 months | 
| All-cause mortality |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary revascularization procedure |  | 60 months | 
| Hospitalization for unstable angina |  | 60 months | 
| Composite of MI, stroke, unstable angina hospitalization or coronary revascularization |  | 60 months | 
| End-stage renal disease (ESRD) |  | 60 months | 
| Bone fracture |  | 60 months | 
| Diabetic ketoacidosis (Inpatient, primary position) |  | 60 months | 
| Diabetic ketoacidosis (Inpatient, any position) |  | 60 months | 
| Severe hypoglycemia |  | 60 months | 
| Urinary tract cancers |  | 60 months | 
| Lower-limb amputation |  | 60 months | 
| Acute kidney injury (Inpatient, primary) |  | 60 months | 
| Acute kidney injury (Inpatient, any position) |  | 60 months |