Semaglutide Reduces Insulin Needs by 22.6% in Type 1 Diabetes Patients With Obesity | Research

The takeaway

In adults with type 1 diabetes and obesity, semaglutide reduced total daily insulin dose by 22.6% over 26 weeks, with early reductions driven primarily by a direct drug effect rather than weight loss.

22.6% insulin dose reduction
Total daily insulin dropped over 26 weeks, with bolus insulin accounting for the largest decrease (-30.5%). At week 4, 83% of the reduction was independent of weight loss.

What the researchers found

Over 26 weeks, semaglutide produced a 22.6% reduction in total daily insulin dose (95% CI: -28.3 to -17.0), driven by a 30.5% reduction in bolus insulin and 15.6% reduction in basal insulin. The basal/TDD ratio increased from 0.56 to 0.62. Insulin dose decreased from 0.72 to 0.60 units/kg/day.

Mediation analysis showed that at week 4, 83% of the TDD reduction (-11.1 U/day) was a direct drug effect and only 17% (-2.3 U/day) was from weight loss. By week 26, it was 52% direct effect (-11.4 U/day) and 48% weight loss (-10.5 U/day). Daily carbohydrate intake decreased from 137g to 107g.

Why it matters

Type 1 diabetes with obesity is a growing problem, and high insulin doses contribute to weight gain, creating a vicious cycle. Semaglutide's ability to reduce insulin needs — especially mealtime insulin — while also promoting weight loss could break this cycle. The finding that most of the early insulin reduction is a direct drug effect (not dependent on weight loss) is particularly important, as it means patients see benefits almost immediately. This could improve quality of life by simplifying insulin management and reducing hypoglycemia risk.

How the study worked

This was a post hoc analysis of the ADJUST-T1D trial, a double-blind, multicenter, randomized, placebo-controlled trial of semaglutide 1 mg/week in adults with type 1 diabetes and obesity using automated insulin delivery systems. Changes in total daily insulin dose, basal and bolus insulin, carbohydrate intake, and user-initiated bolus counts were analyzed over 26 weeks using linear mixed models. Mediation analysis separated the direct drug effect from weight-loss-mediated insulin reduction.

What this study cannot tell us

This is a post hoc analysis (not pre-specified), which limits the strength of causal conclusions. The specific sample size is not stated in the abstract. The study lasted only 26 weeks, so long-term effects on insulin needs are unknown. All participants used automated insulin delivery systems, which may limit generalizability to patients on manual insulin regimens. The mediation analysis assumes that weight loss and direct drug effects are the only pathways, which may oversimplify the mechanism.

How to read the evidence

This is a post hoc analysis of a randomized, double-blind, placebo-controlled trial (ADJUST-T1D) — the gold-standard trial design. While the post hoc nature means these specific outcomes were not pre-specified, the underlying trial data is high quality. The mediation analysis adds mechanistic insight but relies on modeling assumptions.

When this study was published

Published in 2025 in Diabetes Care, a top-tier diabetes journal. This represents the latest data on semaglutide in type 1 diabetes, an area of active clinical investigation.

The bigger picture

GLP-1 agonist peptides were developed for type 2 diabetes, where they stimulate insulin secretion. Their use in type 1 diabetes — where the pancreas produces little or no insulin — is an emerging frontier. This study demonstrates that semaglutide's benefits in T1D go beyond weight loss to include direct effects on insulin sensitivity and appetite. As automated insulin delivery systems become standard care, understanding how adjunctive peptide therapies interact with these systems is critical for optimizing management.

Questions still open

Does the insulin dose reduction with semaglutide lead to fewer hypoglycemic events in type 1 diabetes patients using automated insulin delivery?
Would higher semaglutide doses (2.4 mg/week as used for obesity) produce even greater insulin reductions in T1D?

Common questions

Can people with type 1 diabetes take semaglutide even though they still need insulin?

Yes — semaglutide doesn't replace insulin in type 1 diabetes (where the body cannot make its own insulin), but it can be used alongside it. In this study, semaglutide reduced how much insulin patients needed by lowering appetite and carbohydrate intake, improving insulin sensitivity, and having direct effects on blood sugar regulation. Patients still used their automated insulin pumps throughout.

Why did bolus (mealtime) insulin drop more than basal insulin?

Semaglutide slows stomach emptying and reduces appetite, leading patients to eat fewer carbohydrates (from 137g to 107g per day). Since mealtime insulin doses are calculated based on carbohydrate intake, eating less directly translates to needing less bolus insulin. Basal insulin also decreased, likely due to improved overall insulin sensitivity from weight loss and semaglutide's direct metabolic effects.

Read the original research

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.

Diabetes care

View on PubMed ↗Publisher’s paper ↗

Citation

Karakus, Kagan E; Akturk, Halis K; Kruger, Davida; Ahmann, Andrew; Bharvaga, Anuj; Langel, Christine R; Ackeifi, Courtney A; Rosen, Jonathan; Pyle, Laura; Snell-Bergeon, Janet K; Shah, Viral N. (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.. Diabetes care. https://doi.org/10.2337/dc25-2249