Early insulin dose cuts with semaglutide in type 1 diabetes were mostly independent of weight loss

A post hoc analysis of the ADJUST-T1D trial found that weekly semaglutide reduced total daily insulin doses in adults with type 1 diabetes and obesity, and that the earliest dose cuts came mostly from a direct drug effect rather than from weight loss ^[1]. The analysis was published in Diabetes Care ^[1].

The underlying trial was double-blind, multicenter, randomized and placebo-controlled, testing semaglutide 1 mg per week in adults with type 1 diabetes and obesity who used automated insulin delivery systems ^[1]. Over 26 weeks, total daily insulin dose fell 22.6% (95% CI −28.3 to −17.0) ^[1]. Bolus insulin dropped more than basal insulin: −30.5% (95% CI −39.5 to −21.5) for bolus versus −15.6% (95% CI −21.5 to −9.7) for basal ^[1]. The basal share of total insulin rose from 0.56 to 0.62, and insulin per kilogram of body weight fell from 0.72 to 0.60 units/kg/day (P < 0.001 for both) ^[1].

The new element is a mediation analysis that separated the drug's direct effect from the effect of weight loss. At week 4, 83% of the reduction — about 11.1 units per day — was attributed to a direct drug effect, and 17% — about 2.3 units per day — to weight loss ^[1]. By week 26 the two were close to even: 11.4 units per day (52%) from the direct effect and 10.5 units per day (48%) from weight loss ^[1].

Because this is a post hoc analysis, it looks back at data from a trial built to answer a different question, and on its own it does not establish cause and effect ^[1]. Participants were adults who had both type 1 diabetes and obesity and who used automated insulin delivery systems, so whether the same pattern holds for people with type 1 diabetes who do not have obesity, or who use other ways of delivering insulin, has not been established ^[1].

A commentary published in the same issue discusses shared strategies for type 1 and type 2 diabetes management and early lessons from GLP-1 trials in type 1 diabetes ^[1].

Why it matters for patients

For people with type 1 diabetes, insulin remains the core treatment; in this trial semaglutide was used alongside insulin as an adjunct, not as a replacement ^[1]. Semaglutide is also marketed as Ozempic, Wegovy and Rybelsus.

An average 22.6% fall in total daily insulin over 26 weeks is a substantial change, and because bolus insulin fell more than basal insulin, it points to shifts in how mealtime and background dosing are balanced ^[1]. In the trial those changes were made under a research protocol with clinical oversight, and the analysis does not offer guidance on adjusting insulin outside that setting ^[1].

The timing may matter as much as the size. Doses came down early, and at week 4 most of that drop was not explained by weight loss ^[1]. That suggests insulin needs can change before much weight comes off, although the analysis does not say whether the same holds for people outside this specific group ^[1].

The analysis does not report new safety findings, and it does not address how these dose reductions compare with other approaches to treating obesity in type 1 diabetes ^[1].

What happens next

The analysis appears in Diabetes Care volume 49, issue 5, after online publication on December 22, 2025 ^[1]. No further trials or regulatory steps in type 1 diabetes are described in the paper ^[1]. Whether semaglutide will be studied or reviewed more broadly for type 1 diabetes has not been announced ^[1].