Type 1 Diabetes TrialNet: Leading the Charge in Disease Prediction, Prevention, and Immunotherapeutic Mechanistic Understanding

Abstract

Established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2001, Type 1 Diabetes TrialNet (TrialNet) is an international consortium of clinical research centers that studies the development of type 1 diabetes and performs clinical studies aimed at delaying or preventing the disease. In recognition of NIDDK's 75th anniversary, this review will summarize the major findings, accomplishments, and future opportunities of its long-running program TrialNet. More than 20 intervention, observational, and mechanism-directed clinical studies have been conducted in collaboration with thousands of people living with type 1 diabetes and their families. New and repurposed immunotherapies have been successful in stages 2 and 3 of type 1 diabetes, contributing to the U.S. Food and Drug Administration approval of the first disease-modifying therapy to delay the onset of type 1 diabetes. Mechanistic findings continue to drive ongoing and future trial designs including novel combination therapies. TrialNet has several ongoing trials, with several for early stages of type 1 diabetes in development. There are new initiatives within TrialNet for community engagement, increasing clinical trial representation, personalizing treatments, and training the next generation of translational investigators.

Graphical abstract

Figure 1

Number of people screened for autoantibodies in TrialNet history. In the first year of the Pathway to Prevention study, there were 341 relatives of individuals with type 1 diabetes screened for islet autoantibodies. Each dot represents the total number of individuals, cumulatively, who had been screened when a protocol amendment occurred that modified the screening or monitoring process. The number of relatives screened climbed steadily and in 2024 exceeded a quarter of a million individuals (depicted by the red line).

Figure 2

The Type 1 Diabetes TrialNet Ribbon was developed as a tool to convey the stages of type 1 diabetes to participants, clinicians, and investigators. Once at stage 1 (the presence of multiple autoantibodies and normoglycemia) the disease of type 1 diabetes begins, as the lifetime risk of progressing to symptomatic disease approaches 100%. In stage 2, in addition to multiple islet autoantibodies, dysglycemia is present, representing a higher-risk stage and more imminent clinical diagnosis (stage 3). The clinical studies conducted and ongoing within TrialNet are presented above each respective stage. DZB, daclizumab; MMF, mycophenolate mofetil; T1D, type 1 diabetes.