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Semaglutide in Nonalcoholic Fatty Liver Disease

Phase 4
Completed
Conditions
Non-alcoholic Fatty Liver Disease
Interventions
Registration Number
NCT05813249
Lead Sponsor
Zagazig University
Brief Summary

The goal of this clinical trial is to test the therapeutic effect of Semaglutide in NAFLD and its sequelae in obesity and/or type 2 diabetes mellitus. The main question it aims to answer is:

• Is the use of Semaglutide (oral or subcutaneous form) effective in improving NAFLD and its sequelae in obesity and/or type 2 diabetes mellitus?

Participants will undergo:

* Abdominal ultrasound.

* Fibroscan with controlled attenuation parameter to assess liver stiffness (kPa) and liver steatosis (dB/m).

* Fibrosis-4 score requires values of age, alanine aminotransferase, aspartate aminotransferase, and platelet count.

* NAFLD Fibrosis Score requires values of age, BMI, platelet count, albumin, hyperglycemia, and ALT/AST ratio.

Researchers will compare:

* Group 1 will receive oral Semaglutide for 48 weeks.

* Group 2 will receive injectable Semaglutide for 48 weeks.

* Group 3 will receive Pioglitazone and/or Vitamin E. to see if there is an improvement in liver stiffness and severity of hepatic steatosis after 48 weeks.

Detailed Description

Rationale:

NAFLD is one of the major causes of chronic liver disease worldwide with the highest prevalence in Middle East countries. No pharmaceutical agent until now approved to treat hepatic steatosis. There is a potential effect of glucagon-like peptide-1 agonists in the treatment of steatosis and improving the resulting steatohepatitis and fibrosis in obesity and/or type 2 diabetes mellitus.

Research question:

Is the use of Semaglutide (oral or SC form) effective in improving NAFLD and its sequelae in obesity and/or type 2 diabetes mellitus?

Hypothesis:

The investigators hypothesize that Semaglutide (oral or SC form) has a role in NAFLD associated with obesity and/or type 2 diabetes mellitus.

Aim of the study:

To determine the therapeutic effect of Semaglutide in NAFLD and its sequelae in obesity and/or type 2 diabetes mellitus.

Objectives:

* Determine the therapeutic effect of oral and SC Semaglutide in NAFLD and its sequelae in obesity and/or type 2 diabetes mellitus.

* Compare oral and SC forms of Semaglutide.

* Evaluate the impact of the medication on glycemic control and weight loss.

Material and methods:

1. Site of study:

This study will be conducted in Internal Medicine Department, at Zagazig University Hospitals.

2. Type of study:

This study is an open-label clinical trial.

3. Subjects allocation:

* Group 1: patients receive oral Semaglutide for NAFLD complicating obesity and/or type 2 diabetes.

* Group 2: patients receive SC Semaglutide for NAFLD complicating obesity and/or type 2 diabetes.

* Group 3: patients receive conventional drug therapy for NAFLD (vitamin E and/or pioglitazone) complicating obesity and/or type 2 diabetes.

* The patients receive medication at their own expense from a private pharmacy.

4. Steps of performance and techniques:

* Full medical history taking.

* Complete physical examination for all patients, calculating body mass index.

* Local examination of the liver.

* Calculation of BMI and measurement of waist circumference.

* Liver function tests.

* Complete blood count.

* Kidney function tests.

* Lipid profiles include total cholesterol, triglyceride, LDL, and HDL.

* Glucose metabolisms include fasting plasma glucose and HbA1c.

* Abdominal ultrasound.

* Fibroscan with CAP to assess liver stiffness (kPa) and liver steatosis (dB/m).

* FIB4 requires values of age, ALT, AST, and platelet count.

* NFS requires values of age, BMI, platelet count, albumin, hyperglycemia, and ALT/AST ratio.

* Group 1 will receive oral Semaglutide with starting dose of 3mg daily then up-titration to 14 mg for 48 weeks. Group 2 will receive injectable Semaglutide starting with 0.25mg SC weekly for 4 weeks and up-titration gradually to reach 2mg SC weekly for 48 weeks. Group 3 will receive Pioglitazone and/or Vitamin E.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
180
Inclusion Criteria
  • Patients diagnosed with NAFLD by non-invasive methods in the form of abdominal US or MRI, confirmed by a Fibroscan scan with CAP to assess the quantity of hepatic steatosis and severity of fibrosis up to 21 weeks before the start of the study and after treatment.
  • Primary obesity with body mass index (BMI) > 30.
  • Type 2 diabetes mellitus.
Exclusion Criteria
  • Type 1 diabetes mellitus.
  • DM, which is treated with insulin glargine.
  • Alcohol consumption.
  • Patients had bariatric surgery.
  • Hepatitis C virus, hepatitis B virus, HIV.
  • Patients with peptic ulcer disease.
  • Secondary obesity originated from hypothalamic or endocrinal disorders.
  • Other causes of CLD.
  • Decompensated liver disease.
  • History of pancreatitis (acute or chronic).
  • Hepato-biliary disorders.
  • ALT and AST values > 5 times of upper normal limits.
  • Severe cardiac disease.
  • Patients treated with GLP-1 agonist within 90 days before screening.
  • Patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NAFLD1Rybelsus Oral ProductHepatic steatosis
NAFLD2Ozempic Injectable ProductHepatic steatosis
NAFLD3Tocopherol and/or ActosHepatic steatosis
Primary Outcome Measures
NameTimeMethod
NAFLD regression48 weeks

improvement of severity of hepatic steatosis evaluated by CAP (dB/m)

Secondary Outcome Measures
NameTimeMethod
Fibrosis regression48 weeks

improvement of liver stiffness evaluated by Fibroscan (kPa) and

Trial Locations

Locations (1)

Zagazig University

🇪🇬

Zagazig, Sharkia, Egypt

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