Effect of Oral Semaglutide on Liver Fat and Body Composition in Liver Transplant Recipients With Diabetes Mellitus

• Status: Recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with insulin resistance and associated disorders, such as obesity, type 2 diabetes, metabolic syndrome, and dyslipidemia.

It has been noted that several individuals with liver transplantation develop nonalcoholic fatty liver disease in the transplanted liver. This is because of the presence of various risk factors of obesity and NAFLD, such as decreased physical activity, that persist following liver transplantation. Post-liver transplant patients are particularly at risk for developing NAFLD, as these patients are on oral steroids and immunosuppressants for a significant period of time.

There is no medication approved for the prevention or treatment of NAFLD. Semaglutide is an GLP-1 receptor agonist that have been approved for the treatment of type 2 diabetes and obesity. Semaglutide has also been demonstrated to have beneficial effects on NAFLD. However, there is no data on the effect of semaglutide on liver fat accumulation or changes in body composition in patients following liver transplantation. Therefore, the current pilot study is planned to evaluate the effect of oral semaglutide on the liver fat, liver enzymes and body composition in patients undergoing liver transplantation

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medanta, The Medicity, India
• Treatments: Semaglutide

Criteria

Inclusion Criteria:

1. A man or woman, 30 years of age or above with liver transplantation of at least 3 months duration who meets all the following two criteria:

1. On standard anti-diabetic agents (metformin and/or insulin) with an HbA1c of <=9% at screening

2. Body mass index of >25 kg/m2

2. Subjects must be medically stable based on medical history, physical examination, and laboratory investigations.

3. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

4. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of the study and are willing to participate in the study.

Exclusion Criteria:

1. History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.

2. History of brittle or labile glycemic control, with widely varying glucose measurements by FPG or SMBG such that stable glucose control over the treatment period would be unlikely.

3. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 3 years before Screening, or an Alcohol Use Disorders Identification Test (AUDIT) with a score >=8, or alcohol consumption of more than 20 g per day in the case of women and more than 30 g per day in the case of men for at least three consecutive months during the previous 5 years.

4. Thyroid stimulating hormone (TSH) value that is either < 0.45 mIU/L or >10 mIU/L at Screening.

Note: Subjects on thyroid hormone replacement therapy must be on a stable dose and dosing regimen for at least 4 weeks prior to enrollment.

5. Use of a PPAR-γ agonist [e.g., a thiazolidinedione (pioglitazone], an SGLT2 inhibitor (e.g., canagliflozin, empagliflozin, dapagliflozin) or GLP-1 receptor agonists (e.g., liraglutide, dulaglutide) within 12 weeks before the enrollment.

6. Ongoing eating disorder, or a significant weight loss or weight gain within 12 weeks before the Screening visit, defined as an increase or decrease of 5% in body weight based upon clinic-based measurement or, if not available, based on subject's report.

7. Myocardial infarction, unstable angina, pulmonary hypertension, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3 months before Screening, or revascularization procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease.

8. Use of vitamin E within 4 weeks before screening.

9. History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper gastrointestinal surgical procedure (including gastric resection).

10. History of diabetic gastroparesis (or symptoms suggestive of this disorder, including postprandial bloating or vomiting), malabsorption, inflammatory bowel disease, or any other chronic, clinically important gastrointestinal disorder.

11. Estimated glomerular filtration rate (eGFR) <45 mL/min/1•73 m2 using the Modification of Diet in Renal Disease Study (MDRD) equation.

12. Subjects with a history of having or possibly having metallic material in the body or any contraindication for a MR examination.

13. Claustrophobia, or anxiety related to previous negative experiences with magnetic resonance imaging procedures or if the subject is unwilling to participate in magnetic resonance imaging procedures.

14. Clinically important hematologic disorder (e.g., symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia) at Screening.

15. History of human immunodeficiency virus (HIV) antibody positive at Screening.

16. Contraindications to the use of oral semaglutide (per ORAL SEMAGLUTIDE Prescribing Information).

17. Pregnancy or women breastfeeding or planning to become pregnant while enrolled in this study.

18. History of significant cardiac, vascular, pulmonary, renal, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric disturbances.

19. Patients with history of myopathies or evidence of active muscle disease.