Abstract
Introduction and Objective: Metabolic endpoints are being explored for treatment response in T1D prevention trials. Measures combining both insulin secretion and sensitivity could be more sensitive markers of treatment effect in clinical trials. Methods: We compared OGTT-derived AUC C-peptide and C-peptide index (CPI) as measures of secretion, and the oDI (AUC Insulin*Matsuda Index) as a measure of β-cell function including both secretion and sensitivity in two TrialNet trials in Stage 1 (TN18, Abatacept for 12 months) and Stage 2 (TN10, Teplizumab for 14 days) T1D. We compared measures over time and after 2 years of treatment between treated and placebo arms. Results: In TN10, Teplizumab had a greater effect on AUC C-peptide (p=0.008) and CPI (p<0.001) compared to placebo after 2 years; oDI did not differ (p=0.241). Conversely, in TN18, oDI was higher in the Abatacept arm compared to placebo (p<0.001) with no differences in AUC C-peptide (p=0.270) and CPI (p=0.194). Further, in TN18, there was a positive change in oDI from baseline in the treated arm (p<0.001), Figure 1. Conclusion: The oDI appears to be more sensitive at detecting differences in Abatacept effect in Stage 1, while C-peptide measures identifies long-term effect of Teplizumab in Stage 2. This could be due to both secretion and sensitivity playing a stronger role in Stage 1, which is better seen over a longer period of time.