In a pilot study described in the latest issue of JAMA, daily treatment with a high-dose oral insulin in children at high risk for type 1 diabetes led to an immune response to insulin without hypoglycemia.

The Pre-POINT study was a double-blind, placebo-controlled, dose-escalation, Phase 1/2 clinical pilot study to evaluate the immune responses and adverse events associated with orally administered insulin in autoantibody-negative, genetically at-risk children. The research was conducted between 2009–2013 in four countries and enrolled 25 islet autoantibody-negative children aged 2– 7 years with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes. The participants were randomized to receive oral insulin or placebo once daily for 3–18 months; nine children received insulin with dose escalations from 2.5 to 7.5mg, 2.5 to 22.5mg, or 7.5 to 67.5mg after six months while six children only received doses of 22.5mg or 67.5mg. The primary outcome was an immune response to insulin, measured as serum IgG and saliva IgA binding to insulin, and CD4+ T-cell proliferative responses to insulin.

Immune responses to insulin were observed in the following participants:

  • 16.7% of those treated with 2.5mg
  • 16.7% of those treated with 7.5mg
  • 33.3% of those treated with 22.5mg
  • 83.3% of those treated with 67.5mg
  • 20% of those treated with placebo

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No cases of hypoglycemia, IgE responses to insulin, autoantibodies to glutamic acid decarboxylase or insulinoma-associated antigen 2, or diabetes were detected during the study. Regardless of the insulin dose, the incidence and type of adverse events did not differ between those receiving placebo and those receiving oral insulin.

The authors conclude that these results support the need for a Phase 3 trial to further assess the efficacy of oral insulin in preventing islet autoimmunity and type 1 diabetes in high-risk children.

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