Semaglutide Treatment for Hyperglycaemia After Renal Transplantation

NCT05702931 | Recruiting Phase 4 DMC

• 1 other identifier: 2022-501170-20-00
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Post-transplant hyperglycaemia occurs frequently in renal transplant recipients within the first two weeks after transplantation. Standard-of-care is primarily based on insulin treatment with the adherent risk of hypoglycaemia and weight gain. Semaglutide produces an effective lowering of plasma glucose in diabetes patients with chronic kidney disease (CKD) and leads to a reduction in weight and the incidence of hypoglycaemia. The efficacy of semaglutide is untested in renal transplant recipients, and safety concerns remain, primarily on renal graft function. Objectives: The primary objective is to establish whether tablet semaglutide (Rybelsus) compared with placebo, both as add-on to standard-of-care, is non-inferior in regulating plasma glucose in patients with hyperglycaemia after renal transplantation. Secondary objectives aim to evaluate the effect of tablet semaglutide on renal graft function, weight, use of insulin, cardiovascular parameters and safety parameters (plasma semaglutide concentration, gastrointestinal side effects, dose of immunosuppressants). Design: An investigator-initiated, placebo-controlled, double-blinded, parallel-group, randomised trial. Population: Patients (n = 104) with post-transplant hyperglycaemia or type 2 diabetes and an estimated glomerular filtration rate (eGFR) \> 15 ml/min/1.73 m2. Methods: Participants diagnosed with post-transplant hyperglycaemia or type 2 diabetes, 10 to 40 days post-transplant, will be randomised 1:1 to either 14 weeks of tablet semaglutide once daily or placebo both as add-on to standard glucose-lowering therapy. Participants will maintain weekly contact with the clinic during the first five weeks and at two to four weeks intervals during the remaining study period. During the trial, each patient will be monitored according to blood laboratory values with safety assessed at every visit by a nephrologist. Pre-prandial plasma glucose will be measured in the morning and evening to adjust glucose-lowering therapy after consultation with an endocrinologist. Double blinded continuous glucose monitoring (CGM) will be performed for 10-14 days from baseline and at weeks 5, 9, and 13. Primary endpoint: \- Mean sensor glucose (mmol/L) evaluated by CGM Key secondary endpoints:

• Incidence of hypoglycaemia
• Body weight (kg)
• Creatinine (μmol/L)
• Daily insulin dose (IE per day)
• Plasma concentration of semaglutide (nmol/L)
• Blood concentrations of cyclosporine and tacrolimus (μg/L)

Conditions

Hyperglycemia; Renal Transplant Complication Primary Non-Function; Diabetes

Outcome Measures

Primary Outcomes (1)

• Mean sensor glucose (mmol/L)

  Mean sensor glucose evaluated by 10 days of CGM obtained at baseline, week 5, week 9 and week 13.

  14 weeks

Secondary Outcomes (29)

• Percentage time in target range (3.9-10.0 mmol/L)

  14 weeks

• Percentage time in hypoglycaemia (level 1 [3.0-3.8 mmol/L] and level 2 [below 3.0 mmol/L])

  14 weeks

• Percentage time in hyperglycaemia (level 1 (10.1-13.9 mmol/L) and level 2 (above 13.9 mmol/L)

  14 weeks

• Glucose variability (standard deviation [mmol/L] and coefficient of variation [%])

  14 weeks

• Glucose management indicator (mmol/mol and %)

  14 weeks

Study Arms (2)

Semaglutide treated group

ACTIVE COMPARATOR

Oral semaglutide once-daily as add-on to standard-of-care for post-transplant hyperglycaemia

Drug: Semaglutide 14 MG [Rybelsus]

Placebo treated group

PLACEBO COMPARATOR

Oral placebo once-daily as add-on to standard-of-care for post-transplant hyperglycaemia

Drug: Placebo

Interventions

Semaglutide 14 MG [Rybelsus] DRUG

At baseline participants will initiate treatment with 3mg of oral semaglutide dosing from weeks 1 to 4. Depending on tolerability the dose will increase to 7 mg daily from weeks 5 to 8 and 14 mg from week 9. Trial medication will be dispensed to subjects for the first time immediately after randomisation and adjusted week 5 and week 9.

Also known as: Rybelsus

Semaglutide treated group

Placebo DRUG

Saline

Placebo treated group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained before any trial-related procedures are performed
• Male or female; age: 18-80 years
• Diagnosis of post-transplant hyperglycaemia 10 to 40 days after transplantation: Fasting plasma glucose ≥ 7.0 mmol/L or an oral glucose tolerance test with at plasma glucose ≥ 11.1 mmol/L or Pre-transplant type 2 diabetes: Receiving glucose-lowring treatment prior to kidney transplantation
• An eGFR \> 15 ml/min/1.73 m2 10 to 40 days after renal transplantation
• Subject must be willing and able to comply with trial protocol

You may not qualify if:

• Type 1 diabetes
• Dialysis
• High risk immunological transplantation (not including ABO-incompatible or re-transplantation)
• Early graft rejection (all rejections verified by biopsy, except borderline rejections. Study initiations can begin 5 days after last dose of rejection treatment with methylprednisolone)
• Chronic pancreatitis/previous acute pancreatitis
• Known or suspected hypersensitivity to trial or related products
• Use of DPP-4 inhibitors within five days prior to screening
• Use of GLP-1RA within 10 days prior to screening
• Malignancy (except basal cell carcinoma)
• Inflammatory bowel disease
• Previous bowel resection
• Cardiac disease defined as decompensated heart failure (New York Heart Association class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last six months
• Any acute condition or exacerbation of chronic condition that would in the investigator's opinion interfere with the initial trial visit schedule and procedures.
• Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant, or are not using adequate contraceptive methods
• Impaired liver function (plasma ALAT \> two times upper reference levels)

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Aarhus University Hospital: collaborator
• Odense University Hospital: collaborator

Study Sites (1)

Department og Nephrology and Endocrinology, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Hyperglycemia; Diabetes Mellitus

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Tobias Bomholt, MD, PhD

CONTACT

+4535457952; Tobias.bomholt@regionh.dk

Mads Hornum, MD, PhD

CONTACT

+453451762; mads.hornum@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Model Details: An investigator-initiated, placebo-controlled, double-blinded, parallel-group, randomised trial.

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 27, 2023
• Study Start: September 19, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-12

Locations

DK (1)