Safety and Efficacy of Oral Semaglutide in Hyperglycaemic Patients After Renal Transplantation

2022-501170-20-00

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)

2024-04-01

2026-04-01

2026-04-01

Not yet recruiting

Early phase I

104

Inclusion Criteria: 1. Written informed consent obtained before any trial-related procedures are performed 2. Male or female; age: 18-80 years 3. Diagnosis of post-transplant hyperglycaemia 10 to 15 days after transplantation: Fasting plasma glucose ≥ 7.0 mmol/L or an oral glucose tolerance test with at plasma glucose ≥ 11.1 mmol/L 4. An eGFR \> 15 ml/min/1.73 m2 10 to 15 days after renal transplantation 5. Subject must be willing and able to comply with trial protocol Exclusion Criteria: 1. Type 1 diabetes 2. Type 2 diabetes pre-transplant (except HbA1c ≤ 55mmol/mol and lifestyle-treated) 3. Dialysis 4. High risk immunological transplantation (not including ABO-incompatible or re-transplantation) 5. Early graft rejection Sema-RTx study 6. Chronic pancreatitis/previous acute pancreatitis 7. Known or suspected hypersensitivity to trial or related products 8. Use of DPP-4 inhibitors within five days prior to screening 9. Use of GLP-1RA within 10 days prior to screening 10. Malignancy (except basal cell carcinoma) 11. Inflammatory bowel disease 12. Previous bowel resection 13. 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 14. Any acute condition or exacerbation of chronic condition that would in the investigator's opinion interfere with the initial trial visit schedule and procedures. 15. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant, or are not using adequate contraceptive methods 16. Impaired liver function (plasma ALAT \> two times upper reference levels) 17. Elevated amylase (plasma amylase \> two times upper reference levels)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'An investigator-initiated, placebo-controlled, double-blinded, parallel-group, randomised trial.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'double-blinded', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 104, 'type': 'ESTIMATED'}}

2024-02-15