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

Inclusion Criteria:

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

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

3. Body mass index of >25 kg/m2

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

5. Subjects must be willing and able to adhere to the prohibitions and restrictionsspecified in this protocol.

6. Each subject must sign an informed consent form (ICF) indicating that he or sheunderstands 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-celltransplantation, or diabetes secondary to pancreatitis or pancreatectomy.

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

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

4. Thyroid stimulating hormone (TSH) value that is either < 0.45 mIU/L or >10 mIU/L atScreening. Note: Subjects on thyroid hormone replacement therapy must be on a stable dose anddosing regimen for at least 4 weeks prior to enrollment.

5. Use of a PPAR-γ agonist [e.g., a thiazolidinedione (pioglitazone], an SGLT2inhibitor (e.g., canagliflozin, empagliflozin, dapagliflozin) or GLP-1 receptoragonists (e.g., liraglutide, dulaglutide) within 12 weeks before the enrollment.

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

7. Myocardial infarction, unstable angina, pulmonary hypertension, revascularizationprocedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3 months before Screening, or revascularization procedure is planned, or subject hasa 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 uppergastrointestinal surgical procedure (including gastric resection).

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

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

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

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

14. Clinically important hematologic disorder (e.g., symptomatic anemia, proliferativebone 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 PrescribingInformation).

17. Pregnancy or women breastfeeding or planning to become pregnant while enrolled inthis 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.