Recent Lessons Learned From Prevention and Recent-Onset Type 1 Diabetes Immunotherapy Trials

  1. Mark A. Atkinson3
  1. 1JDRF, New York, New York
  2. 2Université Paris Descartes, INSERM U1013, Hôpital Universitaire Necker-Enfants malades, Paris, France
  3. 3Department of Pathology, University of Florida, Gainesville, Florida
  1. Corresponding author: Mark A. Atkinson, atkinson{at}

Type 1 diabetes (T1D) results from the immune system’s misguided attack on insulin-producing pancreatic β-cells, leading to lifelong insulin replacement therapy as well as to the risk for developing disease-associated complications (13). Over the past 2–3 decades, the field of clinical research in T1D has seen tremendous growth, including evaluation of a variety of promising immunotherapy approaches for the prevention or reversal of the disorder (46). In just the past 2 years, data from >10 trials have been reported, some revealing promising phase II results. However, phase III trials have failed to demonstrate efficacy. In light of these results, an anxiety-provoked question has arisen: Where does the field go from here? To this end, this article presents and elaborates on key emerging questions and recommendations for future immunotherapy trials in T1D. If implemented successfully, such strategies could accelerate the development of therapies with tangible clinical benefit in T1D because they perhaps more appropriately address the complex nature of the disease.


Nearly 30 years after the first immunotherapy clinical trials in type 1 diabetes (T1D), progress has been realized. This progress includes advancements in scientific knowledge (e.g., immune markers, metabolic testing, pathogenesis), the breadth of agents under investigation (Fig. 1), and how clinical trials are increasingly performed as part of major collaborative networks with uniform protocols often bolstered with mechanistic assays. However, shortcomings remain in demonstrating a degree of therapeutic efficacy for recent-onset T1D immunotherapies that is sufficiently robust in terms of risk/benefit to satisfy the requirements for drug registration and approval by regulatory agencies (i.e., Food and Drug Administration, European Medicines Agency). In 2011 and early 2012 after a number of phase I and II recent-onset clinical trials, a series of phase IIB and III recent-onset T1D trials reported their outcomes (710). In advance …

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