ADJUST-T1D Suggests Semaglutide Efficaciously Treats Type 1 Diabetes, with Viral Shah, MD

At the 85th annual American Diabetes Association conference in Chicago, Illinois, Viral Shah, MD, professor of medicine in the division of endocrinology & metabolism and director of diabetes clinical research at the Center for Diabetes and Metabolic Diseases at Indiana University School of Medicine, presented data from the recent ADJUST-T1D trial investigating the efficacy of semaglutide in patients with type 1 diabetes (T1D).

Although T1D is a widespread disease requiring constant and lifelong insulin therapy, there are few alternative treatments for patients. The automated insulin delivery (AID) mechanism has streamlined the process of insulin delivery, but with GLP-1 RAs largely still in the pipeline, there is a surprising lack of treatments compared to the type 2 diabetes cascade. Shah speaks to this issue.2

“About 100 years from insulin discovery, and we just focused on how to best deliver insulin,” Shah told HCPLive. “Which includes the pump and the AID systems and other things, but nothing else. The only other drug that was approved was pramlintide, which is not used anymore. Versus the type 2 diabetes landscape, where there are so many different options available.”

Shah went on to describe the ADJUST-T1D trial, a double-blind, randomized, placebo-controlled study of adults with type 1 diabetes and a body mass index (BMI) >30 who were not meeting their weight loss goals with the AID system. The study was conducted across 4 centers across the US, and randomized patients to either semaglutide or a placebo.

ADJUST-T1D included 72 patients, with 36 in the semaglutide arm and 36 in the placebo arm. Each patient was followed for 6 months. The trial involved a composite endpoint; patients reaching this endpoint had to achieve continuous glucose monitoring (CGM)-based time between 70 and 180 mg/dL of >70%, time below 70 mg/dL of <4%, and weight reduction of ≥5%.1

“We wanted to have a very holistic approach where you have real improvement in both time and range without increasing time below range and weight loss, so that it’s a more comprehensive health outcome,” Shah said. “This is the first trial that has that primary endpoint.”

Ultimately, a substantially larger portion of the semaglutide group achieved the composite outcome than the placebo group (36% versus 0%; between-group difference, 36 percentage points; 95% CI, 20.6 to 52.2; P <.001). The difference in least-squares mean change from baseline to week 26 for the semaglutide versus placebo group for glycated hemoglobin was -0.3% (95% CI, -.6 to -.05). Percentage of time with CGM glucose levels between 70 and 180 mg/dL had a difference of 8.8% (95% CI, 3.9 to 13.7), and body weight saw a difference of -8.8 kg (95% CI, -10.6 to -7).1

The trial saw only 4 adverse events – 2 instances of hypoglycemia in each cohort. However, all of these were unrelated to semaglutide, as they occurred after the end of the study and due to a pump failure, respectively. No diabetic ketoacidosis was reported, and no decay occurred over the following 6 months.1

“Again, it’s a short-term trial with a small sample size, but at least it’s reassuring that we didn’t have any safety concerns,” Shah concluded. “It’s not a head-to-head comparison, but if you think about the type 2 diabetes trials or obesity trial, it sounds like a pretty similar type of GI.”

Shah reports the following disclosures: Novo Nordisk, Dexcom Inc., Insulet Corporation, Tandem Diabetes Care, and others.

References

1. Shah VN, Akturk HK, Kruger D, et al. Semaglutide in adults with type 1 diabetes and obesity. NEJM Evidence. Published online June 23, 2025. doi:10.1056/evidoa2500173

2. Infante M, Silvestri F, Padilla N, et al. Unveiling the Therapeutic Potential of the Second-Generation Incretin Analogs Semaglutide and Tirzepatide in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults. J Clin Med. 2025;14(4):1303. Published 2025 Feb 15. doi:10.3390/jcm14041303