In adults with type 1 diabetes mellitus (T1DM)  and obesity, how much of insulin dose reduction during semaglutide treatment is related to weight loss rather than a direct drug effect? In Diabetes Care, a post hoc analysis of the Adjunct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D) trial evaluated longitudinal changes in insulin dosing. 

ADJUST-T1D was a double-blind, multicenter, randomized, placebo-controlled trial that assessed semaglutide 1 mg administered once weekly in adults with T1DM and obesity. Over 26 weeks, changes in total daily insulin dose (TDD), basal insulin dose, bolus insulin dose, carbohydrate intake, and user-initiated bolus counts were analyzed using linear mixed models. Mediation analysis was used to quantify the relative contributions of direct semaglutide effects and weight loss to insulin dose reduction.

From baseline to week 26, semaglutide treatment was associated with a 22.6% reduction in TDD (95% confidence interval [CI] −28.3 to −17.0). Bolus insulin dose declined by 30.5% (95% CI −39.5 to −21.5), compared with a 15.6% reduction in basal insulin dose (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 expressed as units per kilogram per day declined from 0.72 to 0.60 (P < 0.001). At week 4, 83% of the TDD reduction was attributed to a direct drug effect, while at week 26 the reduction was evenly divided between direct effect and weight loss. Daily carbohydrate intake declined from 137 g at baseline to 107 g at week 26.

These findings indicate that semaglutide treatment was associated with rapid, sustained, and predominantly bolus-driven insulin dose reductions in adults with T1DM and obesity.