Herein, the authors ascertained if oral insulin could delay the onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. Based on the findings, it was deduced that oral insulin at a dose of 7.5 mg/d did not delay or prevent the development of type 1 diabetes over 2.7 years, compared with placebo. Hence, this trial did not support use of oral insulin for diabetes prevention.

Methods

• This study consisted of relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance.
• The candidates were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany between March 2, 2007, and December 21, 2015.
• The main study group (n = 389) comprised of first-phase insulin release on an intravenous glucose tolerance test which appeared to be higher than the threshold.
• The 55 patients in the secondary stratum 1 constituted an identical antibody profile as the main study group with the exception that they had first-phase insulin release that was lower than the threshold.
• In this trial, the secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations.
• Follow-up was carried out through December 31, 2016.
• The enrollees were allocated to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), with the inclusion of subjects in the main study group who received oral insulin (n = 203) or placebo (n = 186).
• The primary outcome included time to diabetes in the main study group.
• Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs were reported.

Results

• Among 560 randomized candidates (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed this study including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group.
• Diabetes was diagnosed in 58 individuals (28.5%) in the oral insulin group and 62 (33%) in the placebo group, during a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group.
• Time to diabetes did not appear to be notably different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P=.21).
• Diabetes was diagnosed in 13 individuals (48.1%) in the oral insulin group and in 19 enrollees (70.3%) in the placebo group, in secondary stratum 1 (n = 55).
• Substantially longer time to diabetes was determined with oral insulin (HR, 0.45; 95% CI, 0-0.82; P=.006).
• The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was discovered to be 1.03 (95% CI, 0-2.11; P=.53).
• For the entire cohort of 560 subjects, it was disclosed to be 0.83 (95% CI, 0-1.07; P=.11), which were not notably different.
• Infection (n = 254) was found to be the most common adverse event, with 134 events in the oral insulin group and 120 events in the placebo group.
• However, there were no occurrences of significant study-related adverse events.