High-Dose Oral Insulin Did Not Delay Progression of Type 1 Diabetes in Children: Study

A recent trial which involved children with early stage type 1 diabetes (T1D) found that high-dose oral insulin did not slow disease progression. After 12 months, rates of dysglycemia and progression to clinical diabetes were similar between the insulin and placebo groups. The findings published in the journal of Diabetes Care suggest no significant preventive benefit of oral insulin at this stage.

Insulin itself is a key autoantigen in childhood T1D, making it a prime target for immune-based prevention strategies. Studies have theorized that oral administration of insulin could induce “immunological tolerance,” a process in which the immune system becomes less reactive to a specific antigen. This concept has shown promise in preclinical studies and earlier-stage investigations.

This research tested whether high-dose oral insulin could slow progression in children diagnosed with stage 1 T1D, a presymptomatic phase marked by the presence of diabetes-related autoantibodies but normal blood sugar levels.

The study enrolled 220 children, including 112 girls, with a median age of 4.8 years. The participants were randomly assigned to receive either daily oral insulin (110 children) or placebo (110 children) for 12 months. The dosing regimen consisted of 7.5 mg per day for the first 3 months, followed by 67.5 mg per day for the remaining 9 months.

This study tracked the time from study enrollment to development of dysglycemia (abnormal blood glucose) or clinical diabetes, and whether treatment increased immune responses to insulin within the first year as primary outcomes.

After one year, 179 participants completed the trial. Dysglycemia or overt diabetes developed in 87 children overall (46 in the oral insulin group and 41 in the placebo group). The hazard ratio was 1.07, which indicated a nearly identical risk, and the 5-year progression rate stood at 40% in both groups.

The therapy also failed to significantly alter immune responses. Among the first 90 children evaluated for immune outcomes, 25% of those receiving oral insulin showed an increased immune response to insulin, when compared to 31% in the placebo group. One notable finding was a modest interaction with the INS rs689 genotype, suggesting that genetic background may influence response to therapy. 

Also, the treatment proved safe and well tolerated. No significant study-related adverse events were reported. Overall, the findings suggest that one year of high-dose oral insulin does not prevent or delay progression from stage 1 T1D to clinical disease. 

Source:

Ziegler, A.-G., Albeer, A., Arnolds, S., Assfalg, R., Bunk, M., Daniel, C., Hofelich, A., Jacobsen, S., Kick, K., Knoop, J., Kohls, M., Kordonouri, O., Matzke, C., Pfirrmann, M., Ramminger, C., Sarcletti, K., Scholz, M., Schütte-Borkovec, K., Serr, I., … Achenbach, P. (2026). Effect of high-dose oral insulin in children with stage 1 type 1 diabetes: The Fr1da insulin intervention randomized controlled trial. Diabetes Care. https://doi.org/10.2337/dc25-2818