Moving from Insulin Substitution to the Treatment of the Underlying Autoimmune Disease in Type 1 Diabetes.

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Currently, a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first FDA-approved disease-modifying treatment of preclinical stage 2 diabetes. Research of drugs like golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40 ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes, albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies.