In adults with two or more antibodies predicting the development of type 1 diabetes, treatment with daily oral insulin therapy did not prevent development of the disease, but a small subset experienced a 31–month delay in clinical diabetes development.

“It’s important to note, this delay in disease development was not the primary endpoint, nor the primary group, so overall, the trial results were negative,” Carla J. Greenbaum, MD, of the Benaroya Research Institute in Seattle, said during a press conference announcing the findings. “Nonetheless, this dramatic result in the secondary analysis remains something we wish to follow up on.”

In a previous randomized, placebo–controlled trial involving participants with what is often called “stage 1” type 1 diabetes — relatives of patients with type 1 diabetes with positive antibodies predicting the disease but normal glucose tolerance — treatment with 7.5 mg daily oral insulin did not delay or prevent the development of clinical type 1 diabetes in the cohort, Greenbaum said. However, in a post hoc analysis, researchers identified a subgroup with specific antibodies who did experience a delay in disease development compared with those assigned placebo.

To build on those findings, Greenbaum said, Type 1 Diabetes TrialNet, an international clinical trial network funded by the NIH, conducted a new study to explore the role of oral insulin therapy in delaying type 1 diabetes in relatives of those with the disease with similar characteristics.

Greenbaum and colleagues analyzed data from 560 individuals considered to have stage 1 type 1 diabetes after screening more than 140,000 people in the TrialNet network.

Researchers randomly assigned participants to 7.5 mg oral insulin daily or placebo; participants underwent an oral glucose tolerance test every 6 months. Participants were stratified by antibody type: The primary stratum included participants positive for islet cell antibodies (ICA) or insulinoma antigen 2 and glutamic acid decarboxylase (IA2+GAD) antibodies (n = 389); secondary stratum one included participants positive for ICA+ or IA2+GAD (n = 55); secondary stratum two included participants positive for IA2 or GAD (n = 114); secondary stratum three included participants positive for IA2 or GAD (n = 2).

In the primary stratum, researchers observed no between–group differences in the rate of progression to type 1 diabetes during 96 months of follow–up, Greenbaum said. Similar results were observed in secondary stratum two and secondary stratum three.

“What was surprising, however, was the results from secondary stratum one,” Greenbaum said. “This was 55 people with the same antibodies, but also with lower amounts of insulin secretion, and thus were more likely to progress more rapidly.”

In this particular group, Greenbaum said, researchers observed an average 31–month delay in progression to clinical type 1 diabetes in those receiving oral insulin therapy vs. those assigned placebo.

“This result further supports our understanding that not everyone develops type 1 diabetes the same way, and this research is an early step toward developing specific and targeted therapies,” Greenbaum said, adding that TrialNet has three other ongoing studies using different therapies to determine whether the progression to type 1 diabetes can be delayed or halted.

“Since relatives of people with type 1 diabetes have a 15 times increased risk of developing diabetes themselves, we urge relatives of those with diabetes to join us in stopping clinical diabetes,” Greenbaum said.