Semaglutide for the Prevention Of Post-Transplant Diabetes Mellitus

Phase 2

Not yet recruiting

• Conditions: Kidney Transplant Recipient
• Interventions: Drug: Semaglutide 3 MG [Rybelsus]; Drug: Placebo Oral Tablet; Drug: Semaglutide 7 MG [Rybelsus]; Drug: Semaglutide 14 MG [Rybelsus]

• Registration Number: NCT06913023
• Lead Sponsor: University Health Network, Toronto

Brief Summary

The study aims to determine the short-term efficacy, mechanisms and safety of 24 weeks of placebo and semaglutide therapy in 74 KTR at risk of post-transplant diabetes mellitus (PTDM).

Detailed Description

A kidney transplant is the best treatment for people living with kidney failure as it allows people to live longer with a better quality of life. However, one in four kidney transplant recipients will develop diabetes after transplant. This is largely due to the medications that must be used to prevent rejection of the transplant. Kidney transplant recipients who get diabetes after transplant are up to three times more likely to have heart disease and die prematurely. To date, there are no treatments to prevent the development of diabetes after kidney transplant. Semaglutide is a drug that is commonly used to treat diabetes and obesity. The investigators believe that semaglutide is a safe and effective drug which can prevent the development of diabetes in kidney transplant recipients. Therefore, the investigators are conducting a study where kidney transplant recipients who are at increased risk of developing diabetes after transplant are randomly assigned to receive either semaglutide or placebo for 24 weeks after their transplant. The study will determine whether semaglutide is effective in decreasing blood sugar levels and the rate of diabetes. The investigators will also study other important markers of health including body weight and cholesterol levels as well as liver, kidney and heart function. Diabetes after transplant is a common problem, and preventing it is extremely important to allowing kidney transplant recipients to live longer and better lives. The results of this study will allow the investigators to determine if semaglutide is a safe and effective option for the prevention of diabetes in kidney transplant recipients.

Study Timeline

• Study First Submitted: 2025-03-17
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-02
• Last Update Submitted: 2025-04-02
• Study First Posted: 2025-04-06
• Last Update Posted: 2025-04-06
• Study Start: 2026-01-05
• Primary Completion: 2027-11-30
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

1. Signed and dated written informed consent.

2. Adult (≥18 years) recipients of a living or deceased donor kidney transplant

3. Between 4- and 12-weeks post kidney transplant

4. Stable kidney function defined as an eGFR > 30 ml/min/1.73m2 (CKD-EPI)

5. At risk for PTDM at the time of transplant based on the following criteria:

   1. BMI ≥ 25 kg/m2, or
   2. Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or
   3. 2hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or
   4. HbA1C 5.5-6.4% (at risk for DM or prediabetes).

Exclusion Criteria

1. Established diagnosis of type 1 or type 2 DM as per Diabetes Canada (including the need for glucose-lowering therapy for hyperglycemia at the time of screening)
2. Kidney-Pancreas transplant recipient
3. Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
4. History of pancreatitis
5. Personal or family history of medullary thyroid cancer or MEN2B
6. Women who are pregnant, nursing or plan on becoming pregnant whilst in the trial
7. Use of GLP1RA in the 30 days prior to screening
8. Contraindication to MRI (applicable only to those undergoing the optional MRI assessments)
9. With known or suspected hypersensitivity to semaglutide or related products
10. Patient not able to understand and comply with study requirements, based on Investigator's judgment.
11. Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcom
12. History of glucose-galactose malabsorption syndrome

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide	Semaglutide 3 MG [Rybelsus]	Patients will be up-titrated as tolerated starting at 3 mg oral semaglutide once daily for 4 weeks, followed by 7 mg oral semaglutide once daily for 4 weeks and then 14 mg oral semaglutide once daily for 16 weeks. Semaglutide can be down-titrated to previously tolerated dose if the current dose is not tolerated by the participant.
Semaglutide	Semaglutide 7 MG [Rybelsus]	Patients will be up-titrated as tolerated starting at 3 mg oral semaglutide once daily for 4 weeks, followed by 7 mg oral semaglutide once daily for 4 weeks and then 14 mg oral semaglutide once daily for 16 weeks. Semaglutide can be down-titrated to previously tolerated dose if the current dose is not tolerated by the participant.
Semaglutide	Semaglutide 14 MG [Rybelsus]	Patients will be up-titrated as tolerated starting at 3 mg oral semaglutide once daily for 4 weeks, followed by 7 mg oral semaglutide once daily for 4 weeks and then 14 mg oral semaglutide once daily for 16 weeks. Semaglutide can be down-titrated to previously tolerated dose if the current dose is not tolerated by the participant.
Placebo	Placebo Oral Tablet	-

Primary Outcome Measures

Name	Time	Method
2-hour OGTT	24 weeks	The primary outcome of this study is the change in plasma glucose at 120 minutes following a 75g oral glucose challenge (2-hour OGTT) at 24 weeks. The 2-hour OGTT was selected as the primarily outcome in this study for the following reasons: 1) In selecting a surrogate outcome for PTDM in KTR, there are limitations to HbA1c and fasting glucose in this population; 2) The 2-hour OGTT is the recommended test for the diagnosis of PTDM in KTR and 3) The use of OGTT has been used in other PTDM prevention studies.

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	24 weeks	: The side effects of GLP-1RA have been well described and will be assessed at each study visit. Adverse events include AKI, hypoglycemia, volume depletion, GI intolerance, amputations, pancreatitis, hepatobiliary complications and injection site or allergic reactions, infectious complications (any source), and malignancy. Episodes of biopsy-proven acute rejection (as defined by the Banff criteria), death-censored graft failure (defined as the need for initiation of chronic dialysis or re-transplantation) or death with graft function (defined as death with a functioning allograft) will also be collected. Kidney transplantation assures complete denervation of the transplanted kidney and the renal vasoconstrictive response in the setting of intravascular volume depletion is diminished in KTR. Therefore, frequent monitoring for adverse events has been integrated in our study design, occurring on 10 separate occasions, to capture these adverse events should they occur.
Estimated GFR	24 weeks	Calculated by CKD-EPI 2021 equation
Change in fasting blood glucose	24 weeks
GFR	24 weeks	Measured using 24-urine collection for creatinine, standardized per 1.73m2 body surface area. And estimated using CKD-EPI 2021 equation.
Urinary glucose excretion	24 weeks	Measured using a 24-hour urine collection for glucose
Change in serum insulin	24 weeks
Change in HbA1c	24 weeks
Albuminuria	24 weeks	measuring urine albumin excretion from a 24-hour urine collection
Natriuresis	24 weeks	Assessed with a 24-hour urine collection for sodium excretion
Percentage of body fat	24 weeks	Bioimpedance analysis
Change in fasting lipid profile	24 weeks
Change in liver enzymes	24 weeks	ALT and AST
Change in fibrosis level	24 weeks	Transient elastography
Change in steatosis level	24 weeks	Transient elastography
Change in waist circumference	24 weeks
Change in body weight	24 weeks
Systolic blood pressure	24 weeks
Diastolic blood pressure	24 weeks
Mean arterial pressure	24 weeks
Percentage of extracellular fluid	24 weeks	Bioimpedance analysis

Trial Locations

Locations (2)

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada