We sought to determine whether a measure combining changes in C-peptide and glucose could show efficacy 3 months after teplizumab treatment among multiple islet autoantibody+ dysglycemic individuals (n=44, age 19.2± 11.9 yrs on teplizumab and n=32, age 17.5± 11.1 yrs on placebo) in the recent TrialNet teplizumab prevention trial (teplizumab delayed T1D onset). In the 2D analysis assessing changes in glucose and C-peptide below (Figure), mean glucose and C-peptide from 30 to 120 minutes are plotted from baseline and 3-month OGTTs. For each OGTT, centroids (central point of OGTT shape) are connected by vectors, showing opposite directionality from baseline to 3 months between groups. Since AUC C-peptide/AUC glucose (AUC Ratio) correlates highly with centroid C-peptide/centroid glucose (r=0.99), to quantify the differences in directionality, we compared AUC Ratio (x1,000; adjusted for baseline) change from baseline to 3 months. The teplizumab group showed a positive change in AUC Ratio: 1.5±2.9 vs. a negative change in placebo: - 0.78±2.7; p=0.001). This difference was sustained after 6 months of treatment (p=0.004).
In summary, a 2D analysis of glucose and C-peptide change provided visual and quantitative evidence of an early treatment effect. As a centroid correlate, the AUC Ratio can be a useful endpoint for performing shorter prevention trials.
E.K. Sims: None. M.V. Warnock: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. J. Sosenko: None.
National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; JDRF
