Semaglutide for the Prevention Of Post-Transplant Diabetes Mellitus (SPOT-DM)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant Recipient
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Semaglutide 3 MG [Rybelsus]; Drug: Semaglutide 7 MG [Rybelsus]; Drug: Semaglutide 14 MG [Rybelsus]

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 Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Vesta Lai; Phone Number: 8508 416-340-4800; Email: vesta.lai@uhn.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
      • Contact: Vikas S Srinivasan, MD FRCPC; Phone Number: 604-806-8970; Email: vsrinivasansridhar@providencehealth.bc.ca
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital
      • Contact: Vesta Lai; Phone Number: 8508 416-340-4800; Email: vesta.lai@uhn.ca
      • Principal Investigator: Sunita Singh, MD MSc FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Oral Tablet; Placebo tablet
Experimental: Semaglutide; 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.	Drug: Semaglutide 3 MG [Rybelsus]; Semaglutide 3mg for 4 weeks.; Drug: Semaglutide 7 MG [Rybelsus]; Semaglutide 7mg for 4 weeks.; Drug: Semaglutide 14 MG [Rybelsus]; Semaglutide 14mg for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-hour OGTT	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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure		24 weeks
Change in body weight		24 weeks
Change in waist circumference		24 weeks
Change in HbA1c		24 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	: 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.	24 weeks
Estimated GFR	Calculated by CKD-EPI 2021 equation	24 weeks
Change in fasting blood glucose		24 weeks
GFR	Measured using 24-urine collection for creatinine, standardized per 1.73m2 body surface area. And estimated using CKD-EPI 2021 equation.	24 weeks
Urinary glucose excretion	Measured using a 24-hour urine collection for glucose	24 weeks
Change in serum insulin		24 weeks
Albuminuria	measuring urine albumin excretion from a 24-hour urine collection	24 weeks
Natriuresis	Assessed with a 24-hour urine collection for sodium excretion	24 weeks
Percentage of body fat	Bioimpedance analysis	24 weeks
Change in fasting lipid profile		24 weeks
Change in liver enzymes	ALT and AST	24 weeks
Change in fibrosis level	Transient elastography	24 weeks
Change in steatosis level	Transient elastography	24 weeks
Diastolic blood pressure		24 weeks
Mean arterial pressure		24 weeks
Percentage of extracellular fluid	Bioimpedance analysis	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in kidney oxygenation (R2*)	Assessed via blood oxygenation dependent magnetic resonance imaging (BOLD-MRI) in an optional cohort.	24 weeks
Change in kidney fibrosis (ADC)	Assessed via blood oxygenation dependent magnetic resonance imaging (BOLD-MRI) in an optional cohort.	24 weeks

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Sunita Singh, MD MSc FRCPC, University Health Network, Toronto General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 5, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: 25-5093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No