LAUSR

BACKGROUND Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive destruction of the pancreatic beta-cells leading to a lifelong dependence on insulin. It is associated with an increased morbidity and mortality from diabetes-related complications and a significant treatment burden. However, there has been a substantial progress in therapeutic strategies that can affect the course of the disease. SUMMARY This review addresses advances in immunotherapy aimed at preserving residual beta-cell function in individuals with a recent onset of T1D, and arresting the disease in pre-symptomatic stages. Recent and ongoing clinical trials have investigated the efficacy and safety of various immunotherapeutic strategies aimed at targeting several mechanisms of autoimmunity, which are thought to be important in disease pathogenesis, and therapies that also address beta cell health. So far, T cell-directed therapies that led to a favourable balance between T effector cell depletion or modulation and preservation or expansion of regulatory T cells have shown the most success. Furthermore, regarding the timing of intervention, teplizumab was the first immunomodulatory agent to demonstrate a significant delay in disease progression in high-risk individuals before clinical onset. KEY MESSAGES As more targeted immune interventions with potentially fewer side effects are closer to the translation into clinical practice, some new challenges may need to be addressed. The use of combination approaches that include immunotherapeutic strategies targeting different aspects of the immune system and interventions that improve beta cell health may be required, along with the use of individualized patient-tailored approaches, a move towards early intervention, and a focus on patient-reported outcome measures.