Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Type 2 Diabetics

NCT02932436 | Completed Phase 4

• 2 other identifiers: UMCM-2016EPI052016-001264-11
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the EmDia trial is to compare the effects of empagliflozin with placebo in addition to standard diabetic treatment or dietetic treatment on cardiac diastolic function in patients with type 2 Diabetes mellitus.

Conditions

Diabetes Mellitus, Type 2; Diastolic Dysfunction

Keywords

empagliflozin; diastolic function; poorly controlled type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• difference in E/E' ratio between 12 weeks after baseline and at baseline

  difference in E/E' ratio (noninvasive surrogate marker for left ventricular diastolic function (LVEDP) measured by 2D-echocardiography) between 12 weeks after baseline and at baseline

  12 weeks

Secondary Outcomes (21)

• difference in E/E' ratio (change from baseline (V1) to 1 week follow-up)

  1 week

• difference in Left ventricular systolic function (LVEF)

  1 week

• difference in Left ventricular systolic function (LVEF)

  12 weeks

• difference in Left end-diastolic volume (LEDV)

  1 week

• difference in Left end-diastolic volume (LEDV)

  12 weeks

Other Outcomes (17)

• difference in biomarkers of cardiac diseases

  1 week

• difference in biomarkers of cardiac diseases

  12 weeks

• difference in biomarkers of vascular diseases

  1 week

Study Arms (2)

Empagliflozin

EXPERIMENTAL

10 mg Empagliflozin daily per os for 12 weeks

Drug: Empagliflozin

Placebo

EXPERIMENTAL

amount of Placebo corresponding to empagliflozin 10 mg daily per os for 12 weeks

Drug: Placebo

Interventions

Empagliflozin DRUG

10 mg per os daily for 12 weeks

Also known as: Jardiance

Empagliflozin

Placebo DRUG

amount of Placebo corresponding to empagliflozin 10 mg per os daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting all of the following criteria at visit 0 (screening) will be considered for admission to the trial:
• Diagnosis of type 2-diabetes mellitus with stable glucose-lowering background therapy and/or dietetic treatment for at least 12 weeks
• In subjects without glucose-lowering background therapy: the application of Metformin was considered to be unsuitable due to drug intolerance
• HbA1c level of ≥6.5% and ≤10.0% at visit 0 (screening) for subjects on antidiabetic background therapy or HbA1c level of ≥6.5% and ≤9.0% for drug-naïve subjects with dietetic treatment
• Diastolic cardiac dysfunction E/E' ratio ≥8 (2D-echocardiography)
• Age 18 - 84 years
• BMI ≤ 45 kg/m² (Body Mass Index)
• For women: post-menopausal for more than 12 months without an alternative medical cause can participate in the trial. Women with childbearing potential can only participate, if they are surgically sterile or a negative pregnancy test (serum or urine) is available at visit 1 and they are willing to practice highly effective birth control method during trial. Reliable highly effective contraception comprises
• combined (estrogen and progesteron containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• progesteron-only hormonal contraception associated with inhibition of ovaluation (oral, injectable, implantable)
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner (provided that partner is the sole sexual partner and that the vasectomised partner has received medical assessment of the surgical success)
• sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

You may not qualify if:

• Subjects presenting with any of the following criteria at visit 0 (screening) will not be included in the trial:
• Pretreatment with empagliflozin or other SGLT2 inhibitor within the last 3 months
• Pretreatment with known inducers of UGT enzymes
• Uncontrolled hyperglycemia with a glucose level \> 240 mg/dl (\>13.3 mmol/L) after an overnight fast
• Impaired renal function, defined as eGFR \<45 ml/min/1.73 m² of body-surface-area
• End-stage renal failure or dialysis
• Severe hepatic dysfunction, defined by serum levels of either SGPT, SGOT, or alkaline phosphatase above 3 x upper limit of normal (ULN)
• Acute urinary tract infection (UTI)
• Known acute genital infection (GI)
• Symptomatic hypotension
• Hematocrit above the upper limit of the reference range
• Hypoglycemic tendencies
• Severe PAD (Fontaine classification Stage IIb - IV)
• Medical history of cancer and/or treatment for cancer within the last 5 years, subjects basalioma can be included in the study
• Medical history of pancreatitis or surgery on pancreas

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kardiologie, Präventive Kardiologie und Medizinische Prävention

Mainz, 55131, Germany

Location

Related Publications (3)

• Bauer KI, Baker D, Lerner R, Koeck T, Buch G, Fischer Z, Martens R, Esenkova EE, Nuber M, Andrade-Navarro MA, Ten Cate V, Tenzer S, Wild PS, Bindila L, Araldi E. Effect of Empagliflozin on the plasma lipidome in patients with type 2 diabetes mellitus: results from the EmDia clinical trial. Cardiovasc Diabetol. 2025 Sep 8;24(1):359. doi: 10.1186/s12933-025-02916-0.

  PMID: 40922034 DERIVED

• Prochaska JH, Junger C, Schulz A, Arnold N, Muller F, Heidorn MW, Baumkotter R, Zahn D, Koeck T, Trobs SO, Lackner KJ, Daiber A, Binder H, Shah SJ, Gori T, Munzel T, Wild PS. Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus-results from the randomized, double-blind, placebo-controlled EmDia trial. Clin Res Cardiol. 2023 Jul;112(7):911-922. doi: 10.1007/s00392-023-02164-w. Epub 2023 Feb 10.

  PMID: 36763159 DERIVED

• Junger C, Prochaska JH, Gori T, Schulz A, Binder H, Daiber A, Koeck T, Rapp S, Lackner KJ, Munzel T, Wild PS. Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study. J Cardiovasc Med (Hagerstown). 2022 Mar 1;23(3):191-197. doi: 10.2459/JCM.0000000000001267.

  PMID: 34939776 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Philipp Wild, MD, MSc

  Johannes Gutenberg University Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 13, 2016
• Study Start: October 10, 2016
• Primary Completion: June 15, 2020
• Study Completion: August 31, 2020
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

DE (1)