Moving from insulin substitution to the treatment of the underlying autoimmune disease in type 1 diabetes.

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.