Once-Weekly Semaglutide Reduces Insulin Needs in Type 1 Diabetes, Suggests Study
USA: In a post hoc analysis of the ADJUST-T1D trial, adults with type 1 diabetes receiving once-weekly semaglutide 1 mg showed a significant reduction in total daily insulin dose by 4 weeks, which was sustained through 26 weeks. Semaglutide use was also associated with fewer user-initiated insulin boluses at all follow-up time points, as reported in Diabetes Care.
The analysis, led by Kagan E. Karakus from the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, and colleagues, explored how semaglutide influences insulin requirements in adults with type 1 diabetes (T1D) and obesity who were using automated insulin delivery systems. While glucagon-like peptide-1 (GLP-1) receptor agonists are not traditionally used in T1D, growing interest surrounds their potential role as adjunct therapies, particularly for patients with obesity and high insulin needs.
The ADJUST-T1D trial was a double-blind, multicenter, randomized, placebo-controlled study evaluating semaglutide 1 mg administered once weekly. In this post hoc analysis, the researchers specifically examined changes in total daily insulin dose, basal and bolus insulin requirements, carbohydrate intake, and the frequency of user-initiated insulin boluses over 26 weeks. Advanced statistical models were used to compare outcomes between the semaglutide and placebo groups, and mediation analyses were performed to distinguish the direct effects of the drug from those related to weight loss.
The study led to the following notable findings:
- Participants receiving semaglutide experienced a substantial and clinically meaningful reduction in overall insulin requirements.
- By 26 weeks, total daily insulin dose decreased by 22.6% compared with baseline.
- The reduction in insulin use was predominantly driven by a decline in bolus insulin rather than basal insulin.
- Bolus insulin requirements fell by more than 30%, while basal insulin doses declined by about 16%.
- The proportion of basal insulin relative to total daily insulin increased, reflecting a shift in insulin dosing patterns.
- Weight-adjusted insulin dose showed a significant decrease over the study period.
- The insulin-sparing effect of semaglutide emerged early, with significant reductions evident as early as four weeks.
- At week 4, most of the insulin dose reduction was attributed to the direct pharmacological effect of semaglutide rather than weight loss.
- By week 26, weight loss accounted for nearly half of the observed reduction in insulin requirements.
- These findings indicate that semaglutide provides both immediate and longer-term benefits through distinct mechanisms.
- Participants treated with semaglutide reported a reduction in daily carbohydrate intake by the end of the study.
- Fewer user-initiated insulin boluses were recorded at all follow-up time points.
- The decrease in bolus frequency suggests reduced need for corrective dosing and potentially improved glycemic stability.
The authors conclude that semaglutide leads to rapid, sustained, and predominantly bolus-driven reductions in insulin requirements in adults with T1D and obesity using automated insulin delivery systems. Early effects appear largely independent of weight loss, highlighting a direct action of the drug on insulin needs. These findings support further investigation into the role of GLP-1 receptor agonists as adjunctive therapies in carefully selected individuals with type 1 diabetes.
Reference:
Kagan E. Karakus, Halis K. Akturk, Davida Kruger, Andrew Ahmann, Anuj Bharvaga, Christine R. Langel, Courtney A. Ackeifi, Jonathan Rosen, Laura Pyle, Janet K. Snell-Bergeon, Viral N. Shah; Effect of Semaglutide on Insulin Dose Reduction in Adults With Type 1 Diabetes and Obesity Using Automated Insulin Delivery Systems: ADJUST-T1D Post Hoc Analysis. Diabetes Care 2025; dc252249. https://doi.org/10.2337/dc25-2249
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