Semaglutide in Nonalcoholic Fatty Liver Disease

• ClinicalTrials.gov Identifier: NCT05813249
• Recruitment Status: Completed
• First Posted: April 14, 2023
• Last Update Posted: April 2, 2024
• Sponsor: Zagazig University
• Information provided by (Responsible Party): Ayman Magd Eldin Mohammad Sadek, Zagazig University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-alcoholic Fatty Liver Disease	Drug: Rybelsus Oral Product; Drug: Ozempic Injectable Product; Drug: Tocopherol and/or Actos	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 180 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapeutic Effect of Semaglutide on Nonalcoholic Fatty Liver Disease in Obesity and/or Type 2 Diabetes Mellitus
• Actual Study Start Date: February 15, 2023
• Actual Primary Completion Date: February 15, 2024
• Actual Study Completion Date: April 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: NAFLD1; Hepatic steatosis	Drug: Rybelsus Oral Product; Oral Semaglutide
Active Comparator: NAFLD2; Hepatic steatosis	Drug: Ozempic Injectable Product; Subcutaneous Semaglutide; Other Name: Wegovy
Active Comparator: NAFLD3; Hepatic steatosis	Drug: Tocopherol and/or Actos; Vitamin E and/or Pioglitazone

Outcome Measures

Primary Outcome Measures :

1. NAFLD regression [ Time Frame: 48 weeks ]
   improvement of severity of hepatic steatosis evaluated by CAP (dB/m)

Secondary Outcome Measures :

1. Fibrosis regression [ Time Frame: 48 weeks ]
   improvement of liver stiffness evaluated by Fibroscan (kPa) and

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

Egypt

Zagazig University

Zagazig, Sharkia, Egypt, 44519

Sponsors and Collaborators

Zagazig University

Investigators

• Principal Investigator: Ayman Sadek, MD; Zagazig University

More Information

• Responsible Party: Ayman Magd Eldin Mohammad Sadek, Associate Professor of Internal Medicine, Zagazig University
• ClinicalTrials.gov Identifier: NCT05813249
• Other Study ID Numbers: ZU-IRB#10461/15-2-2023
• First Posted: April 14, 2023
• Last Update Posted: April 2, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ayman Magd Eldin Mohammad Sadek, Zagazig University:

Semaglutide; Non-alcoholic Fatty Liver Disease; Obesity; Type 2 Diabetes Mellitus

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Tocopherols; Vitamin E; Tocotrienols; alpha-Tocopherol; Semaglutide; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamins; Micronutrients; Glucagon-Like Peptide-1 Receptor Agonists; Hypoglycemic Agents