The mean 2-hour MMTT AUC C-P at 12 months of follow-up has been the primary endpoint for all TrialNet clinical trials of individuals newly diagnosed with T1D. However, it is possible that other measures of C-P responsiveness from MMTTs could provide useful efficacy information for such trials. Thus, we assessed other C-P measures as potential endpoints by substituting them in place of the AUC C-P in completed trials that showed effects of interventions (Rituximab, Abatacept, ATG and ATG+GCSF). These measures included the 30-0 min C-P, AUC C-P partitioned for a response during the first and second hours, peak C-P, as well as AUC C-P/AUC glucose. Estimates for the differences between the treatment and placebo arms were expressed in standard deviation units. The Table below shows differences between treatment and placebo arms along with the significance of the AUC C-P and the substituted endpoint measures for the trials. We found that the differences and their statistical significance were similar to the 2-hour AUC C-P. However, the peak C-P tended to show a wider divergence between the treatment and placebo arms for ATG+GCSF. Our findings show that additional measures of C-P responses could serve as clinical trial endpoints. Other measures of the C-P response besides the AUC could be helpful in assessing the effects of interventions and has potential implications for trials previously considered negative.

H.M. Ismail: None. B.N. Bundy: None. M.A. Atkinson: None. W.V. Moore: None. M.J. Haller: Advisory Panel; Self; Pancreum, SAB Biotherapeutics. W.E. Russell: None. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. K.C. Herold: Consultant; Self; Provention Bio, Roche Pharma. M.J. Redondo: None. J.M. Sosenko: None.


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