Safety and Efficacy of Semaglutide in Kidney Transplant Recipients With Type 2 Diabetes Mellitus or Post-Transplant Diabetes Mellitus: A Retrospective Cohort Study

Abstract

Background: Post-transplant diabetes mellitus and obesity are frequent metabolic complications after kidney transplantation and are associated with increased cardiovascular and graft-related risk. Glucagon-like peptide-1 receptor agonists improve glycaemic control and body weight in type 2 diabetes mellitus and obesity, but their use in kidney transplant recipients remains limited by concerns regarding gastrointestinal intolerance, dehydration-related kidney injury, hepatic safety, and possible interference with calcineurin inhibitor exposure through delayed gastric emptying.
Methods: We conducted a retrospective single-centre cohort study of 15 kidney transplant recipients with either pre-existing type 2 diabetes mellitus or post-transplant diabetes mellitus who were treated with semaglutide. Most patients had follow-up between 12 and 16 months. Primary effectiveness outcomes were changes in glycated haemoglobin and body weight. Safety outcomes included gastrointestinal adverse events, renal graft function, calcineurin inhibitor dose and trough-level stability, rejection episodes, and clinically significant adverse events.
Results: The cohort included 11 men (73.3%) and 4 women (26.7%), with a mean age of 52 +- 13 years. Eleven patients (73.3%) had pre-existing type 2 diabetes mellitus and 4 (26.7%) had post-transplant diabetes mellitus. Semaglutide was initiated approximately 6 weeks after transplantation. Mean baseline glycated haemoglobin was 8.4 +- 1.3%, and mean baseline body weight was 99.5 +- 17.7 kg. During follow-up, semaglutide was associated with clinically meaningful improvement in glycaemic control and reduction in body weight. Fourteen patients (93.3%) received tacrolimus-based immunosuppression and 1 (6.7%) received cyclosporine. Median tacrolimus dose was 3 mg/day (IQR, 2-4), and mean tacrolimus trough level was 7.5 +- 2.2 ng/mL. No clinically significant calcineurin inhibitor interaction or dose adjustment was observed. Serum creatinine remained within approximately 0.9-1.2 mg/dL, estimated glomerular filtration rate remained stable, and no excess rejection signal was identified. Adverse effects were mainly mild gastrointestinal symptoms; two patients (13.3%) discontinued therapy because of nausea. No severe pancreatitis or major treatment-related toxicity was observed.
Conclusions: In this small retrospective kidney transplant cohort, semaglutide was associated with improved metabolic outcomes without apparent adverse effects on graft function or calcineurin inhibitor exposure. Larger prospective transplant-specific studies are needed.