The Metabolic Effects of Empagliflozin in Patients With High Risk of Heart Failure

Empagliflozin to Elderly and Obese Patients With Cardiovascular Disease (Empire Prevent: Metabolic): A Randomized Controlled Trial

The aim of this trial is to assess the effect of Empagliflozin on lipid and glucose metabolism as well as volume homeostasis and renal function in elderly and obese patients with increased risk of developing heart failure. No history of established heart failure or diabetes is allowed.

The primary hypotheses are that 6 months treatment with Empagliflozin 10 mg a day will: 1) decrease epicardial adipose tissue volume, and 2) reduce estimated extracellular volume compared with placebo.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Obesity
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Placebo

Detailed Description

The Empire Prevent: Metabolic is a part of the Empire Prevent Trial Program, which also comprises the Empire Prevent: Cardiac.

The Empire Prevent: Metabolic is designed to enroll at least 120 patients.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body mass index >28kg/m2
• Age 60-84 years
• Established risk factor for developing heart failure, defined as at least one of the following:
• hypertension
• ischemic heart disease
• stroke/transient cerebral ischemia
• chronic kidney disease (eGFR 30-45ml/min/1.73m2)

Exclusion Criteria:

• Diabetes mellitus type 1 or 2 (no medical history, no antidiabetic treatment)
• Heart failure with reduced ejection fraction (LVEF <40%)
• Inability to perform exercise test
• Dementia
• Severe non-compliance
• Substance abuse
• Severe chronic obstructive pulmonary disease (FEV1<50% expected value)
• Permanent atrial fibrillation
• GFR <30 ml/min/1,73m2
• Severe peripheral artery disease
• Cancer treatment within one year beside prostate cancer and basal cell carcinoma
• Severe aortic or mitral valve disease
• Pregnancy or breastfeeding
• Acute hospital admission within 30 days
• Participation in other pharmacological study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active drug (Empagliflozin); Empagliflozin 10 mg, 1 capsule per day	Drug: Empagliflozin 10 MG; Patients are randomized 1:1 to receive either Empagliflozin or matching placebo for 180 days
Placebo Comparator: Inactive drug (placebo); Placebo, 1 capsule per day	Drug: Placebo; Placebo matches the active drug in appearance, odor and labelling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated extracellular volume (eECV)	Between-group difference in the change of eECV assessed by 99mTc-DTPA clearance (technetium-99mTc-diethylenetriaminepentaacetic acid)	180 days
Ventricular epicardial adipose tissue (EAT) mass	Between-group difference in the change of EAT mass assessed by cardiac magnetic resonance imaging (MRI)	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma volume	Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin	180 days
Total pericardial adipose tissue volume	Between-group difference in the change of pericardial adipose tissue volume assessed by cardiac MRI	180 days
Total epicardial adipose tissue (EAT) volume	Between-group difference in the change of EAT mass assessed by cardiac magnetic resonance imaging (MRI)	180 days
Right ventricular end-diastolic volume index, RVEDVI	Between-group difference in the change of RVEDVI assessed by cardiac MRI	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition	Between-group difference in the change in body composition assessed by dual energy x-ray absorptiometry (DXA) scan	180 days
Glucose tolerance	Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test	180 days
Kidney function (measured)	Between-group difference in the change of glomerular filtration rate assessed by 99mTc-DTPA clearance	180 days
Kidney function (estimated)	Between-group difference in the change of estimated glomerular filtration rate (eGFR) based on the chronic kidney disease epidemiology collaboration (CKD-EPI) estimation	180 days
Uric acid	Between-group difference in the change of uric acid	180 days
Urine albumin/creatinine ratio	Between-group difference in the change of urine albumin/creatinine ratio	180 days
Ketone bodies	Between-group difference in the change of ketone supply to the heart assessed by blood ketones	180 days
Erythropoietin	Between-group difference in the change of erythropoietin	180 days
Exploratory outcome: fat tissue gene expression	Between-group difference in fat tissue gene expression assessed by Western Blot	180 days
Exploratory outcome: oxidative stress and inflammation.	Between-group difference in biomarkers of oxidative stress and inflammation.	180 days

Collaborators and Investigators

• Sponsor: Jacob Moller
• Collaborators: Rigshospitalet, Denmark; University Hospital Bispebjerg and Frederiksberg; Hillerod Hospital, Denmark; Herlev and Gentofte Hospital; Danish Heart Foundation
• Investigators: Principal Investigator: Morten Schou, MD, PhD, Herlev-Gentofte Hospital; Principal Investigator: Jacob Eifer Møller, MD, PhD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2021
• Primary Completion (Actual): January 16, 2025
• Study Completion (Actual): January 23, 2025

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Glucose intolerance; Renal function; Lipid metabolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: S-20210028-2

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No