Comparative Effectiveness of Empagliflozin in the US

EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Study Program

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Empagliflozin; Drug: DPP-4 inhibitor; Drug: GLP-1 receptor agonist

• Study Type: Observational
• Enrollment (Actual): 230000

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Bringham Women Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

T2DM eligible patients in Medicare fee for service, plans A, B, D; United Healthcare (Optum Clinformatics Data Mart); MarketScan (Truven Healthcare Analytics)

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with T2DM initiating empagliflozin; Type 2 diabetes mellitus	Drug: Empagliflozin; Empagliflozin; Other Names: JARDIANCE, JARDIANZ, GIBTULIO
patients with T2DM initiating a DPP-4 inhibitor; dipeptidyl peptidase-4 inhibitor treated patients	Drug: DPP-4 inhibitor; dipeptidyl peptidase-4 inhibitor
patients with T2DM initiating a GLP-1 receptor agonist; Glucagon-like peptide-1 receptor agonist treated patients	Drug: GLP-1 receptor agonist; Glucagon-like peptide-1 receptor agonist

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Patorno E, Pawar A, Franklin JM, Najafzadeh M, Deruaz-Luyet A, Brodovicz KG, Sambevski S, Bessette LG, Santiago Ortiz AJ, Kulldorff M, Schneeweiss S. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. Circulation. 2019 Jun 18;139(25):2822-2830. doi: 10.1161/CIRCULATIONAHA.118.039177. Epub 2019 Apr 8.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 5, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: 1245.92

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No