A groundbreaking clinical trial published in NEJM Evidence has shown that once-weekly semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently approved for type 2 diabetes and obesity, may offer significant benefits for adults with type 1 diabetes and obesity when used alongside automated insulin delivery (AID) systems. The 26-week, double-blind, placebo-controlled ADJUST-T1D trial enrolled 72 adults with type 1 diabetes and a body mass index (BMI) of 30 or higher. Participants were randomly assigned to receive either once-weekly semaglutide (up to 1 mg) or a placebo, in addition to their AID therapy. The primary outcome assessed whether participants could achieve a combination of over 70% time-in-range glucose readings (70–180 mg/dL), fewer than 4% of readings below 70 mg/dL, and at least 5% weight loss.
The results showed that a significantly higher proportion of patients in the semaglutide group achieved the primary outcome compared to the placebo group (36% versus 0%, 95% CI: 20.6% to 52.2%; P<0.001). In addition, the semaglutide group showed a mean reduction in HbA1c by 0.3% points, an 8.8% increase in time spent within the target glucose range, and an average weight loss of 8.8 kg. Both groups experienced two episodes of severe hypoglycemia, and no cases of diabetic ketoacidosis (DKA) were reported, highlighting a favorable safety profile.
Further supporting evidence comes from another randomized trial at McGill University Health Centre, where semaglutide led to reduced insulin needs and greater weight loss in patients with type 1 diabetes, particularly those with higher BMIs. Although some participants experienced elevated ketone levels without acidosis, no DKA or severe hypoglycemia occurred. Gastrointestinal side effects were noted, aligning with the known effects of GLP-1 RAs.
These findings underscore semaglutide’s potential as a valuable adjunctive therapy for adults with type 1 diabetes and obesity—a subgroup with limited treatment options. While semaglutide is not currently approved for type 1 diabetes, the promising results from the ADJUST-T1D trial may pave the way for expanded indications and future research. When used alongside AID systems, semaglutide could represent a meaningful advancement in the holistic management of type 1 diabetes.
Reference
- Shah VN, Akturk HK, Kruger D, Ahmann A, Bhargava A, Bakoyannis G, et al. Semaglutide in Adults with Type 1 Diabetes and Obesity. NEJM Evidence. 2025 Jun 23;0(0):EVIDoa2500173.
- Kommu S, Whitfield P. Semaglutide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK603723/
- Pasqua, MR., Tsoukas, M.A., Kobayati, A. et al. Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial. Nat Med 31, 1239–1245 (2025). https://doi.org/10.1038/s41591-024-03463-z