Glycaemic Changes After Semaglutide Discontinuation in Adults With Type 1 Diabetes Using Automated Insulin Delivery: Analysis of the ADJUST-T1D Extension Study

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Abstract

AIMS: To evaluate changes in glycaemic control following semaglutide discontinuation in adults with Type 1 diabetes and obesity who completed the ADJUST-T1D randomised controlled trial. MATERIALS AND METHODS: Continuous glucose monitoring (CGM) data were collected during a 12-week extension phase after the ADJUST-T1D trial. Analyses included participants previously randomised to semaglutide who discontinued treatment (n = 16) and participants previously randomised to placebo who did not receive a glucagon-like peptide-1 receptor agonist during follow-up (n = 22). Changes in CGM-derived metrics from Week 26 to the extension phase were compared using Wilcoxon rank-sum tests with Benjamini-Hochberg adjustment. Analysis of covariance (ANCOVA) adjusting for Week 26 values was performed as a sensitivity analysis. RESULTS: Compared with placebo, participants who discontinued semaglutide experienced a greater decline in time in range (70-180 mg/dL) (median change -3.6% vs. 1.5%; adjusted p = 0.044). Semaglutide discontinuation was also associated with greater increases in glucose standard deviation (6.0 vs. 1.2 mg/dL; adjusted p = 0.044) and coefficient of variation (3.1% vs. 1.1%; adjusted p = 0.044), indicating worsening glycaemic variability. Time above range (> 180 mg/dL) increased numerically but did not remain significant after adjustment (adjusted p = 0.064). No significant between-group differences were observed in hypoglycaemia-related CGM metrics. ANCOVA analyses showed consistent findings. CONCLUSIONS: In adults with Type 1 diabetes and obesity, semaglutide discontinuation was associated with a greater decline in time in range and increased glycaemic variability compared with placebo over 12 weeks. These findings suggest that glycaemic benefits achieved during treatment may not be fully sustained following withdrawal.

Abstract as published, via PubMed.