Beta cell glucose sensitivity identifies clinical response to disease-modifying therapies initiated at stage 3 type 1 diabetes onset – published online 12/03/2026
Carmella Evans‑Molina, Stephen E. Gitelman, Andrea Mari, Ele Ferrannini
Despite promising results from clinical trials initiated at stage 3 type 1 diabetes onset, no therapeutic agent has yet been approved for clinical use. One barrier to advancing approvals has been reliance on C-peptide area under the curve during a mixed-meal tolerance test (AUCCp) as the primary endpoint, as changes in AUCCp do not consistently correlate with clinically meaningful outcomes. In this issue, Evans-Molina et al (https://doi.org/10.1007/s00125-026-06703-8) analysed data from nine Phase II trials performed at stage 3 type 1 diabetes onset to evaluate whether a more physiological measure of beta cell function, beta cell glucose sensitivity (βGS), can improve assessment of therapeutic efficacy. They demonstrate that βGS predicts trial outcomes at earlier time points than AUCCp and that changes in βGS are associated with clinically meaningful differences in glycaemic control. Older age and higher BMI were associated with preservation of βGS and achievement of HbA1c <53 mmol/mol. The authors conclude that these findings position βGS as a clinically relevant endpoint with potential to enhance trial design in type 1 diabetes.