Novel Antidiabetic Medications and Their Effect on Liver Steatosis (NAMELS-18) (NAMELS-18)

Effect of Dulaglutide vs Empagliflozin on Non-alcoholic Fatty Liver Disease of Patients With Type 2 Diabetes Mellitus

The goal of this clinical study is to compare the therapeutic effect of Dulaglutide and Empagliflozin in patients with Diabetes Mellitus type 2 and Non-Alcoholic Fatty Liver Disease. The main question it aims to answer is: Is there a beneficial effect regarding liver steatosis in patients receiving either of these 2 medications and which is more effective? Patients will undergo shearwave elastography, magnetic resonance imaging, and ultrasound. Furthermore, calculation of the Fatty Liver Index (FLI), the Fibrosis-4 Index (FIB-4), as well as the Aspartate Aminotransferase to Platelet ratio Index (APRI) and the NAFLD Fibrosis Score (NFS) will be performed.

Researchers will compare 3 groups:

Group 1 will receive oral Empagliflozin, as add-on to their previous treatment regimen, for 52 weeks.

Group 2 will receive subcutaneous Dulaglutide, as add-on to their previous treatment regimen, for 52 weeks.

Group 3 will receive other optimal antidiabetic treatment (apart from agents of the GLP1-ras or SGLT2-is families) for 52 weeks.

Study Overview

• Status: Completed
• Conditions: Liver Steatosis; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Empagliflozin; Drug: Dulaglutide; Drug: Control Rx

Detailed Description

Rationale:

NAFLD is the most common chronic liver disease worldwide. Presently, relative clinical guidelines focus on weight loss through apporopriate diet and lifestyle. The Glucagon-Like Peptide 1 receptor agonists and the Sodium-Glucose Co-transporter 2 inhibitors constitute novel agents that seem to exert beneficial effects beyond glycemic control. Dulaglutide will be used from the GLP1-ras family and Empagliflozin from the SGLT2-is family.

Research question:

Is the use of Empagliflozin or Dulaglutide effective in improving liver fat fraction in patients with type 2 diabetes mellitus and NAFLD? Which is more beneficial?

Hypothesis:

The investigators hypothesize that both Dulaglutide and Empagliflozin have a role in treating patients with DM2 and NAFLD.

Aim of the study:

To compare the effect of Dulaglutide and Empagliflozin in liver fat fraction of diabetic patients after a year of treatment.

Objectives:

Assess liver steatosis change in patients. Determine percentage of those with >30% liver fat concentration reduction.

Compare Empagliflozin group with Dulaglutide group and Control group. Evaluate the impact of the medications used on glycemic control, weight loss, liver enzymes, lipids and the Fatty Liver Index (FLI), the Fibrosis-4 Index (FIB-4), as well as the Aspartate Aminotransferase to Platelet ratio Index (APRI) and the NAFLD Fibrosis Score (NFS).

Material and methods:

Site of study:

This study will be conducted in the 2nd Department of Internal Medicine of Hippocration General Hospital, and the Therapeutic Department of General Hospital "Alexandra", Athens, Greece.

Type of study:

This is a prospective open-label observational study.

Subjects allocation:

Group 1: patients will receive oral Empagliflozin, as add-on to their previous treatment regimen, for 52 weeks.

Group 2: patients will receive subcutaneous Dulaglutide, as add-on to their previous treatment regimen, for 52 weeks.

Group 3: patients will receive other optimal antidiabetic treatment (apart from agents of the GLP1-ras or SGLT2-is families) for 52 weeks.

Patients receiving Pioglitazone were not included in the study.

Steps of performance and techniques:

Medical history and complete physical examination. Informed consent. Calculation of BMI, measurement of waist and hip circumference. Blood tests including: Liver function tests, Complete blood count, Urea and Creatinine, Lipid profile (total cholesterol, triglycerides, LDL, HDL), fasting plasma glucose and HbA1c.

Abdominal ultrasound, Magnetic Resonance Imaging-Proton Density Fat Fraction, Shearwave Elastography.

Calculation of the Fatty Liver Index (FLI), the Fibrosis-4 Index (FIB-4), as well as the Aspartate Aminotransferase to Platelet ratio Index (APRI) and the NAFLD Fibrosis Score (NFS).

Assessment of changes between date of entry in the study and 52 weeks of treatment.

• Study Type: Observational
• Enrollment (Actual): 78

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 11527
      • "Hippocration" General Hospital of Athens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Caucasian, 25-75 years old, diagnosed with type 2 diabetes mellitus and fatty liver.

Description

Inclusion Criteria:

Presence of diabetes mellitus type 2 and non-alcoholic fatty liver Stable anti-diabetic treatment regimen for the past 6 months

Exclusion Criteria:

Recent (last 5 years) medical history of cancer, pancreatitis, viral hepatitis or any other cause of liver disease (alcohol abuse, autoimmune hepatitis, hemochromatosis, heart failure etc.) Recent alteration (<6 months) of anti-diabetic regimen. Already established treatment with GLP1-ras or SGLT2-is prior to screening. Treatment with Pioglitazone. Corticotherapy administration. Pregnant or planning for pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Empagliflozin group; Oral Empagliflozin 10mg daily, as add-on to their previous treatment regimen.	Drug: Empagliflozin; Empagliflozin 10mg daily, as add-on to previous treatment regimen.; Other Names: E
Dulaglutide group; Subcutaneous Dulaglutide 1.5mg weekly, as add-on to their previous treatment regimen.	Drug: Dulaglutide; Dulaglutide 1.5mg weekly, as add-on to previous treatment regimen; Other Names: D
Control group; Optimal anti-diabetic treatment (apart from agents of the GLP1-ras or SGLT2-is families), targeting glycemic control.	Drug: Control Rx; Optimal anti-diabetic treatment excluding agents of the GLP1-ras or SGLT2-is families.; Other Names: C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Fat Fraction reduction	Change of Liver Fat Fraction as calculated by MRI-PDFF	52 weeks
>30% Liver Fat Fraction reduction	Percentage of each group's participants that achieves >30% Liver Fat Fraction reduction	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c change	Evaluation of HbA1c change in each group	52 weeks
Body Mass Index change	Evaluation of Body Mass Index change in each group	52 weeks
Fatty Liver Index (FLI)	Evaluation of FLI change in each group.	52 weeks
Fibrosis-4 Index (FIB-4)	Evaluation of FIB-4 change in each group.	52 weeks
Aspartate Aminotransferase to Platelet ratio Index (APRI)	Evaluation of APRI change in each group.	52 weeks
NAFLD Fibrosis Score (NFS)	Evaluation of NFS change in each group.	52 weeks
Shearwave Elastography (SWE)	Evaluation of SWE change in each group.	52 weeks

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Hippocration General Hospital; Alexandra Hospital, Athens, Greece
• Investigators: Study Chair: JOHN KOSKINAS, PROFESSOR, National and Kapodistrian University of Athens; Study Director: ANASTASIA THANOPOULOU, AS PROFESSOR, National and Kapodistrian University of Athens; Study Chair: MELANIE DEUTSCH, AS PROFESSOR, National and Kapodistrian University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 14, 2023

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

• Keywords: Empagliflozin; Liver Steatosis; Dulaglutide
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dulaglutide; Empagliflozin
• Other Study ID Numbers: SC12/16-6-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared after analysis is completed and study results have been published. Expected to happen in 1st Semester of 2024. It will include participants' results of imaging and laboratory examinations in excel files.
• IPD Sharing Time Frame: 1 year
• IPD Sharing Access Criteria: Upon request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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