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 and an estimated glomerular filtration rate (eGFR) \> 15 ml/min/1.73 m2.

Methods: Participants diagnosed with post-transplant hyperglycaemia, 10 to 15 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)