Effect of semaglutide on insulin dose requirements in adults with type 1 diabetes and obesity using automated insulin delivery systems: ADJUST-T1D post-hoc analysis

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Objective: In this post-hoc analysis, we used the data from ADJUST T1D trial (double-blind, multicenter, randomized placebo-controlled trial of semaglutide 1 mg/week in adults with type 1 diabetes and obesity), to evaluate the relationship between insulin dose reduction and weight loss. Research Design and Methods: Change in total (TDD), basal, and bolus insulin doses, carbohydrate intake, and user-initiated bolus counts were analyzed using linear mixed models between semaglutide and placebo groups over 26-weeks. Mediation analysis was used to attribute direct effects of semaglutide vs weight loss on insulin dose reduction. Results: From baseline to week 26, there was a significant reduction in TDD by 22.6% (95% CI: −28.3%, −17.0%), which was driven by greater reductions in bolus insulin (−30.5%, 95% CI: −39.5%, −21.5%) than basal insulin (−15.6%, 95% CI: −21.5%, −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, 83% (−11.1U/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 (−11.4U/day; 52%) and weight loss (−10.5 U/day; 48%). Carbohydrate intake decreased from 137 g/day (95%CI:107–167 g) at baseline to 107 g/day (95%CI:76–137 g) at 26 week. Conclusions: Semaglutide produced rapid, sustained, and primarily bolus-driven insulin dose reductions, with early effects largely weight loss-independent in adults with type 1 diabetes and obesity.

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