Teplizumab keeps lid on metabolic decline in individuals at high risk of T1D

A single course of teplizumab treatment can hamper the rapid metabolic decline in people at high risk of type 1 diabetes (T1D), even producing improvements in the metabolic state within 3 months after treatment, and this effect is sustained for at least 6 months, according to a study.

Researchers used data from the TrialNet teplizumab trial to assess whether metabolic endpoints could be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals.

A total of 76 individuals participated in the trial, all of them had sufficient oral glucose tolerance tests (OGTTs) data. The current analysis included 29 placebo-treated and 41 teplizumab-treated individuals at 3 months and 24 placebo-treated and 44 teplizumab-treated individuals at 6 months after randomization.

The researchers then constructed glucose and C-peptide response curves (GCRCs) by plotting mean glucose and C-peptide values from 2-h OGTTs on a two-dimensional grid. The two treatment groups were compared visually for changes in GCRC shape and movement.

In the placebo group, GCRC changes indicated marked metabolic deterioration within 3 months of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. On the other hand, the teplizumab group showed GCRC changes suggestive of metabolic improvement.

Quantitative comparisons, including two novel metabolic endpoints that indicate GCRC changes, were consistent with visual impressions of a favourable treatment effect of teplizumab at the 3- and 6-month time points.

The present data underscore that changes in GCRC grid location and shape, along with corresponding quantitative measures of directionality, can be used to assess the treatment effect in T1D prevention trials.