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.

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/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 U/day) reduction in TDD was due to a direct drug effect, and 17% (-2.3 U/day) was attributed to weight loss, whereas at week 26, the difference was split evenly between direct effect (-11.4 U/day; 52%) and weight loss (-10.5 U/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. CONCLUSIONS: 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.