Liver Transplant; ComplicationsPhase 4NCT05195944
Semaglutide vs Sitagliptin
A Phase 4 study testing Semaglutide Treatment and Sitagliptin 100mg in people with Liver Transplant; Complications and Diabetes Mellitus, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant; Complications, Diabetes Mellitus, NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- Semaglutide Treatment and Sitagliptin 100mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteCanada
- Study dates
- 26 Oct 2022to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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 ().
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- 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.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The GLP-1 Agonist Semaglutide for the Treatment of Metabolic Disease in Liver Transplant Recipients: A Phase IV, Randomized Trial
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.
Read the detailed description
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.
- Conditions
- Liver Transplant; Complications, Diabetes Mellitus, NASH - Nonalcoholic Steatohepatitis, NAFLD
- Being tested
- Semaglutide Treatment, Sitagliptin 100mg
- Medical subject headings
- Diabetes Mellitus, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide TreatmentDrug
The participants will be provided with Semaglutide, titrated up to 14 mg. The starting dose of Semaglutide is 3 mg once daily. At week 4, the dose will be increased to 7 mg once daily. At week 8, the dose will be increased to 14 mg once daily and will be maintained at 14mg until End of Treatment (week 26). Throughout the 26 week treatment period, participants in this arm will also take one "sitagliptin placebo" tablet per day.
Sitagliptin 100mgDrug
participants will take 100mg tablet of Sitagliptin once daily, along with a "semaglutide placebo" pill for the duration of the 26 week treatment period
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | In the Semaglutide Arm, participants will receive daily: 1 tablet of Semaglutide and 1 tablet of Sitagliptin placebo for 26 weeks. The dosages of Semaglutide are 3 mg, 7 mg, and 14 mg. Receives: Drug: Semaglutide Treatment |
| Sitagliptin | Active comparator | In the Sitagliptin arm, participants will receive daily: 1 tablet of 100 mg Sitagliptin and 1 tablet of Semaglutide placebo for 26 weeks. Receives: Drug: Sitagliptin 100mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c level
Evaluate the change in glycemic control and body weight within and between study groups by measuring HbA1c levels and body weight (kg)
Measured: Baseline to 26 weeks
Change in body weight (kg)
Evaluate the change in glycemic control and body weight within and between study groups by measuring HbA1c levels and body weight (kg)
Measured: Baseline to week 26
Secondary outcomes (5)
Change in fasting plasma glucose
Measured: Baseline to 26 weeks
Change in body weight %
Measured: Baseline to 26 weeks
Change in Body mass index (BMI)
Measured: Baseline to 26 weeks
Change in waist circumference
Measured: Baseline to 26 weeks
Number of treatment-emergent adverse events
safety and tolerability of study drugs.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start26 Oct 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Transplant; ComplicationsStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Mamatha Bhat, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05195944
- Sponsor's protocol ID
- 21-5640
- Other IDs
- U1111-1268-1934
- Status last verified
- Mar 2026
- First submitted
- 13 Dec 2021
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The GLP-1 Agonist Semaglutide for the Treatment of Metabolic Disease in Liver Transplant Recipients: A Phase IV, Randomized Trial
- ClinicalTrials.gov ID
- NCT05195944
- Acronym / sponsor ID
- 21-5640
- Conditions
- Liver Transplant; Complications, Diabetes Mellitus, NASH - Nonalcoholic Steatohepatitis, NAFLD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 26 Oct 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: Semaglutide TreatmentIn the Semaglutide Arm, participants will receive daily: 1 tablet of Semaglutide and 1 tablet of Sitagliptin placebo for 26 weeks. The dosages of Semaglutide are 3 mg, 7 mg, and 14 mg. |
| Sitagliptin | Active comparator | Drug: Sitagliptin 100mgIn the Sitagliptin arm, participants will receive daily: 1 tablet of 100 mg Sitagliptin and 1 tablet of Semaglutide placebo for 26 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide TreatmentThe participants will be provided with Semaglutide, titrated up to 14 mg. The starting dose of Semaglutide is 3 mg once daily. At week 4, the dose will be increased to 7 mg once daily. At week 8, the dose will be increased to 14 mg once daily and will be maintained at 14mg until End of Treatment (week 26). Throughout the 26 week treatment period, participants in this arm will also take one "sitagliptin placebo" tablet per day. | Drug | Semaglutide |
| Sitagliptin 100mgparticipants will take 100mg tablet of Sitagliptin once daily, along with a "semaglutide placebo" pill for the duration of the 26 week treatment period | Drug | Sitagliptin |
Primary outcome
Change in HbA1c level
Time frame: Baseline to 26 weeks
Evaluate the change in glycemic control and body weight within and between study groups by measuring HbA1c levels and body weight (kg)
Change in body weight (kg)
Time frame: Baseline to week 26
Evaluate the change in glycemic control and body weight within and between study groups by measuring HbA1c levels and body weight (kg)
5 secondary outcomes
Change in fasting plasma glucose
Time frame: Baseline to 26 weeks
Change in body weight %
Time frame: Baseline to 26 weeks
Change in Body mass index (BMI)
Time frame: Baseline to 26 weeks
Change in waist circumference
Time frame: Baseline to 26 weeks
Number of treatment-emergent adverse events
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mamatha Bhat, MD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide Treatment and Sitagliptin 100mg in people with Liver Transplant; Complications and Diabetes Mellitus, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1c level (time frame: Baseline to 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026; AzTrials last refreshed its copy on 27 Oct 2026.