Through the Fog: Recent Clinical Trials to Preserve β-Cell Function in Type 1 Diabetes

  1. Srinath Sanda1,3
  1. 1Benaroya Research Institute, Seattle, Washington
  2. 2Department of Pediatrics, Division of Endocrinology, University of Florida, Gainesville, Florida
  3. 3Department of Pediatrics, Division of Endocrinology, Seattle Children’s Hospital, Seattle, Washington
  1. Corresponding author: Carla J. Greenbaum, cjgreen{at}benaroyaresearch.org.

Dawn portrays shadows and fleeting openings in the heavy fog. First awake, inquisitive eyes attempt to pierce the grayness, searching out a stepping stone secure enough to settle on next. “There it is, a beam showing a path.” Anxious dreams of the night begin to fade. He prepares to move forward, cautiously choosing the direction. Adjacent, others stir. Where is the path they saw so clearly only a short while before? Now, only nothingness surrounds them. The imperative that first drove them to start the journey appears less urgent. Stuck in place, feet encased in heavy mud, their despair spreads to others. “Surely this direction is wrong. There must be an easier path,” they cry. There is no end to be seen, and we have been traveling many, many years.

—A parable by Carla J. Greenbaum

For almost 50 years, type 1 diabetes has been described as an autoimmune disease characterized by the T-cell–mediated destruction of β-cells, which begins long before clinical diagnosis. Clinical trials accepting this premise and aimed at modulating the immune system before or after onset of clinical disease have failed to prevent or cure type 1 diabetes. Nonetheless, clinical trials have provided useful knowledge. Whereas some studies have demonstrated no effect on disease progression, a small number of therapies have transiently delayed the decline of β-cell function in recently diagnosed patients.

In an effort to move toward new therapies for type 1 diabetes, we must continue to seek out the “openings in the heavy fog” of our parable. A review of recently completed clinical trials provides knowledge to guide the rational design of future trials. In that spirit, this Perspectives in Diabetes article focuses on critical lessons learned from: 1) clinical trials with negative results, 2) pilot studies, and 3) clinical trials demonstrating transient effects on …

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