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.

Abstract

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. 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. 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 76-137) at 26 weeks. Semaglutide produced rapid, sustained, and primarily bolus-driven insulin dose reductions, with early effects being largely independent of weight loss in adults with T1D and obesity.