For children with early type 1 diabetes mellitus (T1DM), preventing progression remains a major unmet need. A phase 2 randomized placebo-controlled trial published in Diabetes Care assessed whether oral insulin could induce immune tolerance and slow disease progression.

The trial enrolled 220 children with stage 1 T1DM and randomly assigned them to daily oral insulin (n=110) or placebo (n=110) for 12 months. Participants received 7.5 mg/day for the first 3 months, followed by 67.5 mg/day for 9 months. Median age was 4.8 years, and 179 participants completed the study. Coprimary outcomes were time to dysglycemia or clinical diabetes and increased immune response to insulin within 12 months.

During follow-up, dysglycemia or diabetes developed in 87 participants, including 46 in the oral insulin group and 41 in the placebo group. Oral insulin did not significantly change progression risk versus placebo (hazard ratio, 1.07; 95% confidence interval, 0.66-1.73; P=0.74). The estimated 5-year progression rate was 40% in both groups. Increased immune response to insulin was observed in 25% of oral insulin recipients and 31% of placebo recipients (P=0.63).

A modest treatment interaction was observed with the INS rs689 genotype, although the overall trial findings remained neutral. Oral insulin was well tolerated, and no significant study-related adverse events occurred. These findings suggest 1 year of high-dose oral insulin did not modify short-term disease progression in children with stage 1 T1DM.