Semaglutide Treatment for Hyperglycaemia After Renal Transplantation

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

Interventions

DRUG

Semaglutide 14 MG [Rybelsus]

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.

DRUG

Placebo

Saline

Sponsors & Collaborators

• Aarhus University Hospital

  collaborator OTHER

• Odense University Hospital

  collaborator OTHER

• Rigshospitalet, Denmark

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-09-19

Primary Completion

2027-12-31

Completion

2027-12-31

Countries

• Denmark

Study Locations