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

Completed
Conditions
Liver Steatosis
Non-Alcoholic Fatty Liver Disease
Interventions
Registration Number
NCT05946148
Lead Sponsor
National and Kapodistrian University of Athens
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
78
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Control groupControl RxOptimal anti-diabetic treatment (apart from agents of the GLP1-ras or SGLT2-is families), targeting glycemic control.
Empagliflozin groupEmpagliflozinOral Empagliflozin 10mg daily, as add-on to their previous treatment regimen.
Dulaglutide groupDulaglutideSubcutaneous Dulaglutide 1.5mg weekly, as add-on to their previous treatment regimen.
Primary Outcome Measures
NameTimeMethod
>30% Liver Fat Fraction reduction52 weeks

Percentage of each group's participants that achieves \>30% Liver Fat Fraction reduction

Liver Fat Fraction reduction52 weeks

Change of Liver Fat Fraction as calculated by MRI-PDFF

Secondary Outcome Measures
NameTimeMethod
Fatty Liver Index (FLI)52 weeks

Evaluation of FLI change in each group.

Aspartate Aminotransferase to Platelet ratio Index (APRI)52 weeks

Evaluation of APRI change in each group.

HbA1c change52 weeks

Evaluation of HbA1c change in each group

Body Mass Index change52 weeks

Evaluation of Body Mass Index change in each group

Fibrosis-4 Index (FIB-4)52 weeks

Evaluation of FIB-4 change in each group.

NAFLD Fibrosis Score (NFS)52 weeks

Evaluation of NFS change in each group.

Shearwave Elastography (SWE)52 weeks

Evaluation of SWE change in each group.

Trial Locations

Locations (1)

"Hippocration" General Hospital of Athens

🇬🇷

Athens, Attiki, Greece

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