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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

Karakus KE, Akturk HK, Kruger D, Ahmann A, Bharvaga A, Langel CR, Ackeifi CA, Rosen J et al.

Diabetes care, 2026

Abstract

OBJECTIVE: In this post hoc analysis, we used the data from the Adjunct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D) trial, a double-blind, multicenter, randomized, placebo-controlled trial of semaglutide 1 mg/week in adults with type 1 diabetes (T1D) and obesity, to evaluate the relationship between insulin dose reduction and weight loss.

RESEARCH DESIGN AND METHODS: Changes between semaglutide and placebo groups over 26 weeks in total daily insulin dose (TDD), basal and bolus insulin doses, carbohydrate intake, and user-initiated bolus counts were analyzed using linear mixed models. Mediation analysis was used to attribute direct effects of semaglutide versus weight loss on insulin dose reduction.

RESULTS: From baseline to week 26, there was a significant 22.6% reduction in TDD (95% CI -28.3 to -17.0), which was driven by greater reductions in bolus insulin (-30.5%; 95% CI -39.5 to -21.5) than basal insulin (-15.6%; 95% CI -21.5 to -9.7). The basal-to-TDD ratio increased from 0.56 to 0.62 (P < 0.001) and insulin dose (in units/kg/day) decreased from 0.72 to 0.60 (P < 0.001) in the semaglutide group. At week 4, an 83% (-11.1 units/day) reduction in TDD was due to a direct drug effect, and 17% (-2.3 units/day) was attributed to weight loss, whereas at week 26, the difference was split evenly between direct effect (-11.4 units/day; 52%) and weight loss (-10.5 units/day; 48%). Daily carbohydrate intake decreased from 137 g (95% CI 107-167) at baseline to 107 g (95% CI…

How strong is the evidence?

Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.

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