Clinical trial NCT05946148: Novel Antidiabetic Medications and Their Effect on Liver Steatosis (NAMELS-18)
Official title: Effect of Dulaglutide vs Empagliflozin on Non-alcoholic Fatty Liver Disease of Patients With Type 2 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-Alcoholic Fatty Liver Disease
Liver Steatosis
Keywords: Empagliflozin
Dulaglutide
Liver Steatosis
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: Alexandra Hospital, Athens, Greece
name: Hippocration General Hospital
First posted: 2023-07-14
Enrollment: 78
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Caucasian, 25-75 years old, diagnosed with type 2 diabetes mellitus and fatty liver.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liver Fat Fraction reduction
timeFrame: 52 weeks
measure: >30% Liver Fat Fraction reduction
timeFrame: 52 weeks
Secondary outcomes:
measure: HbA1c change
timeFrame: 52 weeks
measure: Body Mass Index change
timeFrame: 52 weeks
measure: Fatty Liver Index (FLI)
timeFrame: 52 weeks
measure: Fibrosis-4 Index (FIB-4)
timeFrame: 52 weeks
measure: Aspartate Aminotransferase to Platelet ratio Index (APRI)
timeFrame: 52 weeks
measure: NAFLD Fibrosis Score (NFS)
timeFrame: 52 weeks
measure: Shearwave Elastography (SWE)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Athens
country: Greece
facility: "Hippocration" General Hospital of Athens
state: Attiki
Study officials:
affiliation: National and Kapodistrian University of Athens
name: JOHN KOSKINAS, PROFESSOR
role: STUDY_CHAIR
affiliation: National and Kapodistrian University of Athens
name: ANASTASIA THANOPOULOU, AS PROFESSOR
role: STUDY_DIRECTOR
affiliation: National and Kapodistrian University of Athens
name: MELANIE DEUTSCH, AS PROFESSOR
role: STUDY_CHAIR
References: