Novel Antidiabetic Medications and Their Effect on Liver Steatosis (NAMELS-18)
Condition: Non-Alcoholic Fatty Liver Disease; Liver Steatosis
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Observational

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.
    

Intervention name(s): Empagliflozin; Dulaglutide; Control Rx
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Empagliflozin 10mg daily, as add-on to previous treatment regimen.; Dulaglutide 1.5mg weekly, as add-on to previous treatment regimen; Optimal anti-diabetic treatment excluding agents of the GLP1-ras or SGLT2-is families.
Other intervention name(s): E; D; C
Intervention MeSH terms: Empagliflozin; Dulaglutide
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.
      
Biospecimen description: 
      2 vials of serum taken at each patient visit
    
Keywords: Empagliflozin; Dulaglutide; Liver Steatosis