GLP-1 Receptor Agonists Safely Reduce Weight and HbA1c in Liver Transplant Recipients

Post-liver transplant (LT) weight gain and associated metabolic dysfunction significantly increase the risk of cardiovascular (CV) morbidity, allograft steatosis, and reduce long-term survival. Current management strategies often fall short in this vulnerable population, where immunosuppression regimens can exacerbate metabolic issues. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to promote weight loss and improve cardiometabolic health, but their safety and efficacy specifically in liver transplant recipients (LTRs) have been poorly characterized, leaving a critical clinical gap.

This multicenter retrospective cohort study analyzed adult LTRs treated with GLP-1 RAs across four international centers from 2010-2025. The study included 104 GLP-1 RA users, with 68.3% initiating therapy for diabetes. Subcutaneous semaglutide was the most common agent, used at a median dose of 0.82±0.46 mg weekly. Regular GLP-1 RA users were compared to 116 matched non-users based on age, sex, obesity, diabetes status, transplant year, and center. The primary outcome was change in body weight 1-year post-exposure, with secondary outcomes including glycemic and lipid profiles, kidney/allograft function, immunosuppression effects, MACE, and adverse effects. Longitudinal analyses utilized linear mixed models with multiple imputation.

Among the 104 GLP-1 RA users, treatment led to significant reductions in key metabolic parameters. Body weight decreased by -3.8 kg (-3.9%, p<0.001), and body mass index (BMI) fell by -1.6 kg/m2 (-5.0%, p<0.001). Glycated hemoglobin (HbA1c) also saw a notable reduction of -0.48% (p=0.002), alongside modest improvements in lipid profiles. Liver function tests and immunosuppression trough levels remained stable throughout the treatment period, and importantly, no treatment-limiting adverse events were reported. In matched analyses comparing 80 GLP-1 RA users to 116 non-users:

GLP-1 RAs facilitated a significantly greater weight loss, showing a -3.4 kg difference (p=0.009) compared to non-users. This was accompanied by a -0.43% difference in HbA1c reduction (p=0.042). Crucially, there was no increased risk of allograft dysfunction, T-cell-mediated rejection (TCMR), or major adverse cardiovascular events (MACE) in the GLP-1 RA group.