Immunomodulation in post-transplant diabetes mellitus: Challenges and management

Solid organ transplantation (SOT) in diabetic patients presents unique challenges in balancing immunosuppression, glycemic control, and the risk of infection. Post-transplant diabetes mellitus (PTDM) affects 10 %–40 % of transplant recipients, with immunosuppressive therapies such as corticosteroids and calcineurin inhibitors (CNIs) contributing to insulin resistance and impaired beta-cell function. This review critically examines immunomodulation strategies in diabetic SOT recipients, focusing on optimizing immunosuppressive therapy while mitigating hyperglycemia-related complications. Early glycemic control through insulin therapy, followed by a transition to oral hypoglycemic agents such as metformin, GLP-1 receptor agonists, and DPP-4 inhibitors, has proven effective in reducing PTDM and enhancing long-term transplant outcomes. Alternative immunosuppressive strategies, including belatacept-based regimens and switching from tacrolimus to cyclosporine, offer promising methods to lower PTDM incidence while preserving graft survival. Personalized immunosuppressive regimens tailored to an individual's metabolic risks further improve patient outcomes. Emerging strategies, such as monoclonal antibodies, mesenchymal stem cell therapy, and localized immunomodulation, hold promise for enhancing immune balance while mitigating metabolic complications. A multidisciplinary team involving endocrinologists, transplant surgeons, and diabetes specialists is essential for comprehensive management. Additionally, routine screening for new-onset diabetes after transplantation (NODAT) and early interventions are vital to prevent long-term complications. Despite advancements, gaps remain regarding the long-term metabolic effects of immunosuppressive agents, the optimal timing for transitioning from insulin to oral therapy, and the role of new immunomodulatory treatments. Future research should focus on personalized therapeutic approaches that combine immunosuppressive and metabolic management to improve graft function and patient health. This review highlights the importance of a balanced approach to immunosuppression for diabetic transplant recipients, aiming to enhance survival rates and quality of life.