Impact of Empaglifozine on Cardiac Ectopic Fat (EMPACEF)

There is substantial evidence supporting the fact that ectopic fat accumulation is an important contributor to type 2 diabetes complications and cardiovascular risk [1]. Epicardial adipose tissue (EAT), located between the myocardium and the visceral layer of the pericardium has been associated with atrial fibrillation and with coronary artery disease [2, 3] and its abundance predicts the number of cardiac events within 8 years [4]. In addition, myocardial steatosis has been shown to be an independent predictor of diastolic dysfunction [5] [6]. Furthermore, in type 2 diabetic patients, bariatric surgery can reduce cardiac ectopic fat accumulation and improve cardiac function [7] [8]. When added to standard care, 10 or 25 mg/d of empagliflozin, an inhibitor of sodium-glucose cotransporter 2 (iSGLT2), significantly reduces the risk of death, cardiovascular death, and hospitalisation for heart failure among individuals with type 2 diabetes and established cardiovascular disease when compared to placebo [9]. The mechanisms of empagliflozin-improved cardiovascular outcomes in type 2 diabetic patients at high risk of cardiovascular events are not known. We hypotheses that empaglifozin could modulate cardiac ectopic fat and cardiac metabolism in obese type 2 diabetic patients.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Empagliflozin 10Mg Tab

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years,
• Type 2 diabetes based on the disease diagnostic criteria as described by the WHO,
• HbA1c > 7% and < 10 %
• Stable glucose-lowering therapy for at least 3 weeks before randomization
• Estimated glomerular filtration rate > 60/ml (MDRD)
• Signed informed consent form obtained prior to any study procedure

Exclusion Criteria:

• Evolutive or planned pregnancy during the six months
• Lactation
• Recent weight loss (>5% of body weight within one month),
• Treatment modifying adipose distribution such as corticoids
• Acute coronary syndrome or instable angina during the last 2 months,
• MRI contraindication (metal cardiac valve, pace maker, metal foreign body, claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo group	Drug: Empagliflozin 10Mg Tab; 1 tablet of 10 milligrams per bone 1 time a day during 12 weeks
EXPERIMENTAL: empaglifozine group	Drug: Empagliflozin 10Mg Tab; 1 tablet of 10 milligrams per bone 1 time a day during 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac morphology	magnetic resonance imaging	12 weeks
epicardial adipose tissue volume	magnetic resonance imaging	12weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
myocardial triglyceride	proton magnetic resonance spectroscopy	12weeks
hepatic triglyceride content	proton magnetic resonance spectroscopy	12 weeks
myocardial PCr/ATP ratio		12 weeks

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: anne dutour, Assistance Publique Hopitaux de Marseille

Publications and helpful links

General Publications

• Gaborit B, Ancel P, Abdullah AE, Maurice F, Abdesselam I, Calen A, Soghomonian A, Houssays M, Varlet I, Eisinger M, Lasbleiz A, Peiretti F, Bornet CE, Lefur Y, Pini L, Rapacchi S, Bernard M, Resseguier N, Darmon P, Kober F, Dutour A. Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study. Cardiovasc Diabetol. 2021 Mar 1;20(1):57. doi: 10.1186/s12933-021-01237-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 16, 2017
• Primary Completion (ACTUAL): February 7, 2019
• Study Completion (ACTUAL): February 7, 2020

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (ACTUAL): April 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Cardiac Complexes, Premature; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2016-39; 2016-003196-21 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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