Giving close relatives of people with type 1 diabetes oral insulin did not prevent them from developing diabetes, according to data newly published in the November 21, 2017 issue of the Journal of the American Medical Association.
Detailed results of the study, TrialNet Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus, were first reported at the American Diabetes Association (ADA) meeting in San Diego in June.
The participants were mostly children and adolescents, with a median age of 8, with normal blood glucose but with two or more islet autoantibodies — indicating they would almost certainly develop type 1 diabetes in the future.
They were randomized to 7.5 mg per day of oral insulin (human insulin crystals, Lilly) or placebo, at 87 locations in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany, between March 2007 and December 2015. More than half (57.6%) had a sibling with type 1 diabetes.
They had oral glucose-tolerance tests every 6 months to assess if they had developed type 1 diabetes.
During a median follow-up of 2.7 years, among the 389 participants in the main study group, there was no significant difference in diagnosis of type 1 diabetes, with 58 participants in the oral insulin group (28.5%) and 62 taking placebo (33%) developing it.
Time to diabetes development wasn't different between the two groups (hazard ratio, 0.87; P = 0.21), either.
The study represents the largest-ever trial testing oral insulin, but "these findings do not support oral insulin as used in this study for diabetes prevention," the study authors state.
However, in another group of individuals with the same autoantibodies but with low insulin secretion (n = 55), those who received insulin tablets were diagnosed with type 1 diabetes 2.5 years later than those who got placebo, suggesting there may be a specific subgroup of "responders," one of the researchers, Carla Greenbaum, MD, from Benaroya Research Institute, in Seattle, Washington, suggested at the ADA meeting.
At the time, this was described by one commentator there as a possible "incremental advance."
However, in the current publication, the researchers acknowledge that because there was no adjustment for multiple comparisons in this subgroup, this analysis "must be considered exploratory and hypothesis-generating."
"This trial enrolled participants based on evidence of autoimmunity but did not take into account genetic background, age at onset, and type of first-appearing diabetes-related autoantibody," they note.
"The emerging literature now suggests that future trials need to consider these factors," they conclude.
The Type 1 Diabetes TrialNet Study Group, which supported the trial, is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Center for Research Resources and General Clinical Research Center Award; the Juvenile Diabetes Research Foundation International (JDRF) with awards to European and Australian sites; and the American Diabetes Association. Dr Greenbaum reports serving as an advisor for Eli Lilly. Disclosures for the coauthors are listed in the paper.
JAMA. 2017;318:1891-1902. Abstract
Medscape Medical News © 2017
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