Diabetes CareType 1 DiabetesDecember 22, 2025

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.

Karakus KE, Akturk HK, Kruger D, Ahmann A, Bharvaga A, Langel CR, Ackeifi CA, Rosen J, Pyle L, Snell-Bergeon JK, Shah VN

View on PubMed DOI: pii: dc252249. 10.2337/dc25-2249

Key Finding

Semaglutide helped adults with Type 1 diabetes and obesity reduce their daily insulin dose by 22.6% over 26 weeks, with early effects being mostly due to the drug itself rather than weight loss.

What This Study Found

Think of insulin as fuel for your body's engine, and people with Type 1 diabetes need to carefully measure how much fuel they inject each day. This study looked at what happens when you add semaglutide (a GLP-1 medication) to the mix for people with Type 1 diabetes who are also obese. The researchers found that semaglutide acts like a fuel efficiency booster - it helped people need significantly less insulin while maintaining good blood sugar control. The most dramatic change was in mealtime insulin (bolus), which dropped by 30.5%, while background insulin (basal) only decreased by 15.6%. It's like the difference between needing less gas when you step on the accelerator versus needing less gas when you're idling. Interestingly, the timing tells a story: early on (week 4), about 83% of the insulin reduction was due to semaglutide's direct effects on the body, like a mechanic tuning your engine. But by week 26, it was a 50-50 split between the drug's direct effects and the benefits of weight loss - like getting both a tuned engine and a lighter car.

Statistics Decoded

The 22.6% total insulin reduction (95% CI -28.3 to -17.0) means we're pretty confident the real reduction is somewhere between 17% and 28% - this wasn't just luck. The dramatic 30.5% bolus insulin reduction shows people needed much less mealtime insulin, while the 15.6% basal reduction was more modest. The P < 0.001 values mean these changes were so significant they'd happen by chance less than 1 in 1,000 times - like flipping heads 10 times in a row. The shift in basal/total insulin ratio from 0.56 to 0.62 shows people's insulin needs became more weighted toward background insulin rather than mealtime spikes. Daily carbohydrate intake dropped from 137g to 107g - that's like going from eating 5.5 slices of bread worth of carbs to 4.3 slices per day.

Why This Matters

This is groundbreaking for Type 1 diabetes care because it shows GLP-1 medications can help reduce the insulin burden even when the pancreas produces no insulin naturally - something many doctors weren't sure would work. The rapid, direct effects independent of weight loss suggest semaglutide could help Type 1 patients achieve better glucose control with less insulin right away, potentially reducing hypoglycemia risk and improving quality of life.

Original 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/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. 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.