The effect of once daily dosing of oral Semaglutide versus once daily dosing Sitagliptin on glycemic control, body weight, and safety and tolerability will be compared in Liver Transplant Recipients with poorly-controlled Diabetes Mellitus.

This will be a Phase IV, randomized, parallel, active-controlled, double-blind clinical trial, with one group receiving oral Semaglutide and the other group receiving oral sitagliptin, while continuing any background glucose-lowering medications such as metformin or insulin. Treatment duration will be 26 weeks. Sitagliptin has been chosen as comparator since it is an established oral antidiabetic drug (OAD) within the DPP-4i drug class. There will be a screening period, treatment period, and follow-up period. Furthermore, the investigators will collect biological samples and correlates including serum, plasma, and Intestinal Microbiome samples prior to initiation of study treatment and at the completion of the trial. The investigators will also perform Transient Elastography at these same visits to evaluate change in degree of participant graft steatosis.

Inclusion Criteria:

• Male or female, age ≥18 years at the time of signing informed consent.
• Willing and able to provide informed consent.
• Recipient of liver graft (Liver/Kidney recipients and retransplants allowed)
• Time from transplant surgery ≥ 3 months at time of screening visit with no evidence of active rejection. Liver enzymes must be stable with elevations no greater than 2xULN. However, if patients have elevated liver enzymes beyond 2xULN due to NASH, as confirmed on liver biopsy, they may be included.
• Patient diagnosed with type 2 diabetes or post-transplant diabetes
• Patients transplanted for hepatocellular carcinoma may be included provide their latest surveillance imaging is negative for recurrence
• The use of any immunosuppression regimen (calcineurin inhibitors, mycophenolate mofetil, maintenance prednisone or sirolimus) is acceptable
• HbA1c 6.5-10.5% (53-91 mmol/mol) (both inclusive, not under optimal glycemic control).

For purposes of clarification, patients on stable treatment with one of the following insulin regimens (minimum 10 IU/day) ≥ 90 days prior to the day of screening, may be included (maximum 20% change in total daily dose within the 90 days is acceptable):

• Basal insulin alone
• Basal and bolus insulin in any combination
• Premixed insulin including combinations of soluble insulin Concomitant treatment with stable daily dose of metformin and/or an SGLT2 inhibitor ≥ 90 days prior to the day of screening is allowed.

Being on insulin, metformin, and/or an SGLT-2 inhibitor is optional.

Exclusion Criteria:

• Known or suspected hypersensitivity to trial products or related products.
• Previous participation in this trial.
• Active graft dysfunction that requires investigation (at screening).
• Currently receiving steroids (prednisone) for treatment of acute cellular rejection.
• Patients transplanted for multisystem genetic disorders such as amyloidosis or cystic fibrosis.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly-effective contraceptive methods ().
• Receipt of any investigational medicinal product within 90 days before screening.
• Any disorder or medical condition which, in the investigator's opinion, might jeopardize patient's safety or compliance with the protocol.
• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC).
• History of pancreatitis (acute or chronic).
• History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
• Any of the following: myocardial infarction (MI), stroke or hospitalization for unstable angina or transient ischemic attack within the past 180 days prior to the day of screening and randomization.
• Classified as being in New York Heart Association (NYHA) Class IV.
• Planned coronary, carotid or peripheral artery revascularization known on the day of screening.
• Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term change of insulin treatment for acute illness for a total of ≤ 14 days.
• Known history of proliferative retinopathy or maculopathy requiring acute treatment, unless stable
• History or presence of actively treated malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer, hepatocellular carcinoma, and carcinoma in situ.)