Novel approach for assessing outcomes of type 1 diabetes prevention trials over a fixed time interval

Sims, Emily K., Russell, William E., Cuthbertson, David, Skyler, Jay S., Jacobsen, Laura M., Ismail, Heba M., Redondo, Maria J., Nathan, Brandon M., Carr, Alice L.J., Taylor, Peter N. ORCID: https://orcid.org/0000-0002-3436-422X, Dayan, Colin M. ORCID: https://orcid.org/0000-0002-6557-3462, Galderisi, Alfonso, Herold, Kevan C. and Sosenko, Jay M. 2025. Novel approach for assessing outcomes of type 1 diabetes prevention trials over a fixed time interval. Diabetes , db250310. 10.2337/db25-0310

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Abstract

We evaluated whether a binary metabolic end point for change (Δ) from baseline to 1-year postrandomization could be useful in type 1 diabetes (T1D) prevention trials. Using 2-h oral glucose tolerance testing data from the stage 1 participants in the recent abatacept prevention trial and similar participants in the observational TrialNet Pathway to Prevention (PTP) study, we assessed Δmetabolic measures, plotted glucose and C-peptide response curves, and categorized vectors for Δ from baseline to 1 year as metabolic treatment failure versus success. Analyses were validated using the teplizumab prevention study. PTP participants with Δglucose >0 and ΔC-peptide <0 from baseline to 1 year were at substantially higher risk for stage 3 T1D than those with Δglucose <0 and ΔC-peptide >0 (P < 0.0001). Based on this, we compared placebo versus treatment groups in both trials for failure (Δglucose >0 with ΔC-peptide <0) versus success (Δglucose <0 with ΔC-peptide >0) after 1 year. Using this endpoint, a favorable metabolic impact of abatacept was found after 12 months of treatment. An analytic approach using a binary metabolic end point of failure versus success at a fixed time interval appears to detect treatment effects at least as well as standard primary end points with shorter follow-up.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	American Diabetes Association
ISSN:	0012-1797
Date of First Compliant Deposit:	16 September 2025
Date of Acceptance:	29 July 2025
Last Modified:	16 Sep 2025 11:30
URI:	https://orca.cardiff.ac.uk/id/eprint/180980

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