Have we pushed the needle for treatment of Type 1 diabetes?

•The progression of Type 1 diabetes ½ to 2 years before onset is accelerated.•Immunologics can reduce decline in β cell function over the first 2 years of disease.•Studies of samples from trials have identified how tolerance might be achieved.•Future studies combining immune modulators, regulatory cells, or antigens are needed.

Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of agents with complementary mechanisms of activity.