The Revolutionary Role of GLP-1 Agonists and SGLT-2 Inhibitors in Managing Diabetes and Chronic Kidney Disease in Liver Transplant Recipients

Abstract

Successful liver transplant is the only life-saving intervention for patients with end-stage liver disease, but post-transplant complications, particularly diabetes mellitus and chronic kidney disease, significantly compromise both patient and graft survival. These complications not only heighten clinical and economic burdens but also worsen long-term outcomes due to the rising prevalence of metabolic syndrome, which predisposes many liver transplant recipients to metabolic dysfunctions like diabetes and chronic kidney disease. Additionally, metabolic syndrome is a key driver of Metabolic Associated Steatotic Liver Disease, a leading cause of liver failure and a growing indication for liver transplantation worldwide. While liver transplantation resolves end stage liver disease, it fails to address the underlying metabolic challenges, such as pre-existing or post-transplant diabetes and chronic kidney disease. The use of calcineurin inhibitors ,a cornerstone of immunosuppression, exacerbates these issues by disrupting glucose metabolism, increasing insulin resistance, and causing pancreatic beta-cell dysfunction, which further contributes to post-transplant diabetes mellitus. Post-transplant diabetes mellitus is associated with increased morbidity, mortality, and graft rejection, underscoring the need for improved management strategies. Emerging therapies, such as GLP-1 receptor agonists and SGLT-2 inhibitors, have shown promise in mitigating the effects of diabetes and chronic kidney disease in non-transplant populations. These agents offer potential benefits for liver transplant recipients by improving glycemic control, promoting weight loss, and offering renal protection. However, their application in liver transplantation remains underexplored, with limited clinical data available. This review explores the pathogenesis of diabetes and chronic kidney disease in liver transplant recipients, the challenges posed by current immunosuppressive regimens, and the potential role of GLP-1 agonists and SGLT-2 inhibitors in improving patient and graft outcomes. Future research is essential to optimize post-transplant care and reduce the burden of metabolic complications in liver transplant recipients.