Semaglutide for the Prevention Of Post-Transplant Diabetes Mellitus

NCT06913023 | Not Yet Recruiting Phase 2

• 1 other identifier: 25-5093
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

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).

Conditions

Kidney Transplant Recipient

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  24 weeks

• Estimated GFR

  24 weeks

• Change in fasting blood glucose

  24 weeks

• GFR

  24 weeks

• Urinary glucose excretion

  24 weeks

Other Outcomes (2)

• Change in kidney oxygenation (R2*)

  24 weeks

• Change in kidney fibrosis (ADC)

  24 weeks

Study Arms (2)

Semaglutide

EXPERIMENTAL

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]; Drug: Semaglutide 7 MG [Rybelsus]; Drug: Semaglutide 14 MG [Rybelsus]

Placebo

PLACEBO COMPARATOR

Drug: Placebo Oral Tablet

Interventions

Semaglutide 3 MG [Rybelsus] DRUG

Semaglutide 3mg for 4 weeks.

Semaglutide

Semaglutide 7 MG [Rybelsus] DRUG

Semaglutide 7mg for 4 weeks.

Semaglutide

Semaglutide 14 MG [Rybelsus] DRUG

Semaglutide 14mg for 16 weeks.

Semaglutide

Placebo Oral Tablet DRUG

Placebo tablet

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent.
• Adult (≥18 years) recipients of a living or deceased donor kidney transplant
• Between 4- and 12-weeks post kidney transplant
• Stable kidney function defined as an eGFR \> 30 ml/min/1.73m2 (CKD-EPI)
• At risk for PTDM at the time of transplant based on the following criteria:
• BMI ≥ 25 kg/m2, or
• Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or
• hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or
• HbA1C 5.5-6.4% (at risk for DM or prediabetes).

You may not qualify if:

• 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)
• Kidney-Pancreas transplant recipient
• Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
• History of pancreatitis
• Personal or family history of medullary thyroid cancer or MEN2B
• Women who are pregnant, nursing or plan on becoming pregnant whilst in the trial
• Use of GLP1RA in the 30 days prior to screening
• Contraindication to MRI (applicable only to those undergoing the optional MRI assessments)
• With known or suspected hypersensitivity to semaglutide or related products
• Patient not able to understand and comply with study requirements, based on Investigator's judgment.
• Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcom
• History of glucose-galactose malabsorption syndrome

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Interventions

semaglutide

Study Officials

• Sunita Singh, MD MSc FRCPC

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vesta Lai

CONTACT

416-340-4800; vesta.lai@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study will use a randomized, double-blind, placebo-controlled clinical trial approach comparing semaglutide to placebo in 50 KTR at risk for PTDM. Adult KTR between 4 and 12 weeks after transplant with an eGFR of at least 30 ml/min/1.73m2 at risk for PTDM will be randomized in a 1:1 fashion to either 24 weeks of semaglutide or 24 weeks of placebo.

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: April 6, 2025
• Study Start: January 5, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)