2523-P: Early Glycemic Deterioration and Baseline Risk Prediction of Insulin-Like Growth Factor-1 Receptor Inhibitor Therapy

by sugaradmin



Introduction and Objective: Insulin-like growth factor-1 receptor (IGF-1R) inhibitor has been developed as an effective therapy for thyroid eye disease (TED). However, treatment-associated hyperglycemia remains a clinical concern. We aimed to examine whether early glycemic deterioration during IGF-1R inhibitor therapy is associated with subsequent glycemic trajectories and to develop and validate a risk prediction model.Methods: We analyzed data from three independent randomized clinical trials of the IGF-1R inhibitor IBI311 for TED, including 129 participants treated with IBI311. Two trials served as training cohort (n=76), and the remaining trial served as an independent validation cohort (n=53). Early glycemic deterioration was defined as a ≥0.5% increase in HbA1c by week 6 or initiation/intensification of glucose-lowering therapy within 6 weeks. Associations between early deterioration and glycemic outcomes at treatment completion (24 weeks) were examined in training cohort. A prediction model was developed using baseline metabolic variables with elastic net-regularized logistic regression and externally validated.Results: Early glycemic deterioration occurred in 18.6% (14/129) of participants. Individuals with early deterioration experienced greater increases in HbA1c (1.13% ± 0.55% vs. 0.17% ± 0.33%; P=0.001) and FBG (1.86 ± 1.79 mmol/L vs. 0.16 ± 0.61 mmol/L; P=0.021) at 24 weeks. At baseline, participants with early deterioration had higher FBG, blood pressure, lower HDL-c, and greater metabolic syndrome (MetS) score. An elastic net model incorporating baseline FBG (standard β=0.25) and MetS score (standard β=0.20) demonstrated good discrimination for early deterioration (external AUC 0.80, 95% CI 0.63-0.94).Conclusion: Early glycemic deterioration during IGF-1R inhibitor therapy is associated with subsequent hyperglycemia. A simple baseline model using routinely available metabolic measures may enable early risk stratification.

Disclosure

W. Zhao: None. X. Zhang: None. J. Deng: None. Y. Xu: None. S. Lu: None. L. Ji: None.



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