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

NCT06060392 | Recruiting DMC

• 1 other identifier: MMENDO02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Liver Transplant; Complications; Diabete Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in liver fat content

  Quantified by MRI-PDFF

  Baseline to 24 weeks

Secondary Outcomes (16)

• Change in pancreatic fat content

  Baseline to 24 weeks

• Change in body weight

  Baseline to 24 weeks

• Change in body mass index

  Baseline to 24 weeks

• Change in total fat percentage

  Baseline to 24 weeks

• Change in lean muscle mass

  Baseline to 24 weeks

Study Arms (2)

Oral Semaglutide

EXPERIMENTAL

Patient will receive oral semaglutide

Drug: Semaglutide Pill

Standard of care

NO INTERVENTION

Patient will receive standard of care

Interventions

Semaglutide Pill DRUG

Patient will receive oral semaglutide

Oral Semaglutide

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• On standard anti-diabetic agents (metformin and/or insulin) with an HbA1c of \<=9% at screening
• Body mass index of \>25 kg/m2
• Subjects must be medically stable based on medical history, physical examination, and laboratory investigations.
• Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• 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.

You may not qualify if:

• History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Use of vitamin E within 4 weeks before screening.
• History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper gastrointestinal surgical procedure (including gastric resection).
• 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.
• Estimated glomerular filtration rate (eGFR) \<45 mL/min/1•73 m2 using the Modification of Diet in Renal Disease Study (MDRD) equation.
• Subjects with a history of having or possibly having metallic material in the body or any contraindication for a MR examination.
• 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.
• Clinically important hematologic disorder (e.g., symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia) at Screening.

Sponsors & Collaborators

• Medanta, The Medicity, India: lead

Study Sites (1)

Division Of Endocrinology & Diabetes, Medanta The Medicity

Gurgaon, Haryana, 122001, India

RECRUITING

Related Publications (7)

• Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA; NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021 Mar 25;384(12):1113-1124. doi: 10.1056/NEJMoa2028395. Epub 2020 Nov 13.

  PMID: 33185364 BACKGROUND

• Alkhouri N, Herring R, Kabler H, Kayali Z, Hassanein T, Kohli A, Huss RS, Zhu Y, Billin AN, Damgaard LH, Buchholtz K, Kjaer MS, Balendran C, Myers RP, Loomba R, Noureddin M. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. J Hepatol. 2022 Sep;77(3):607-618. doi: 10.1016/j.jhep.2022.04.003. Epub 2022 Apr 16.

  PMID: 35439567 BACKGROUND

• Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl. 2009 Dec;15(12):1843-51. doi: 10.1002/lt.21943.

  PMID: 19938117 BACKGROUND

• Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy. J Magn Reson Imaging. 2011 Oct;34(4):729-749. doi: 10.1002/jmri.22775. Epub 2011 Sep 16.

  PMID: 22025886 BACKGROUND

• Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012 Jul;36(1):22-9. doi: 10.1111/j.1365-2036.2012.05121.x. Epub 2012 May 3.

  PMID: 22554256 BACKGROUND

• Le TA, Chen J, Changchien C, Peterson MR, Kono Y, Patton H, Cohen BL, Brenner D, Sirlin C, Loomba R; San Diego Integrated NAFLD Research Consortium (SINC). Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology. 2012 Sep;56(3):922-32. doi: 10.1002/hep.25731. Epub 2012 Jul 2.

  PMID: 22431131 BACKGROUND

• Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27.

  PMID: 25482832 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Mr Surender, PhD

CONTACT

01244141414; yadavsurender89@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant, Division Of Endocrinology & Diabetes

Study Record Dates

• First Submitted: September 23, 2023
• First Posted: September 29, 2023
• Study Start: October 30, 2023
• Primary Completion: September 2, 2025
• Study Completion: November 1, 2025
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)