Supplemental_Materials_6.9.21.pdf (470.65 kB)
The Deterrence of Rapid Metabolic Decline within 3 Months after Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes
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posted on 2021-09-22, 16:45 authored by Emily K. Sims, David Cuthbertson, Kevan C. Herold, Jay M. SosenkoEndpoints
that provide an early identification of treatment effects are needed to
implement type 1 diabetes prevention trials more efficiently. To this end, we
assessed whether metabolic endpoints can be used to detect a teplizumab effect
on rapid β-cell decline within 3 months after treatment in high-risk
individuals in the TrialNet teplizumab trial. Glucose and C-peptide response
curves (GCRCs) were constructed by plotting mean glucose and C-peptide values
from 2-hour oral glucose tolerance tests on a 2-dimensional grid. Groups were
compared visually for changes in GCRC shape and movement. GCRC changes
reflected marked metabolic deterioration in the placebo group within 3 months
of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. In
contrast, GCRC changes in the teplizumab group suggested metabolic improvement.
Quantitative comparisons, including two novel metabolic endpoints that indicate
GCRC changes, the Within Quadrant Endpoint (WQE) and the Ordinal Directional
Endpoint (ODE), were consistent with visual impressions of an appreciable
treatment effect at 3 and 6-month timepoints. In conclusion, an analytic
approach combining visual evidence with novel endpoints, demonstrated that
Teplizumab delays rapid metabolic decline, and improves the metabolic state
within 3 months after treatment; this effect extends for at least 6 months.