Viral Shah, MD

The Future of GLP-1s in Type 1 Diabetes, with Viral Shah, MD

New data from the American Diabetes Association’s 85

 Scientific Sessions has highlighted the potential of semaglutide in people with type 1 diabetes. Given these developments, many in endocrinology – and healthcare at large – are wondering if this is the next frontier for glucagon-like peptide receptor agonists (GLP-1 RAs).

Named the ADJUST-T1D study and presented by 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, these data showed a significant reduction in fat mass in patients with T1D who received semaglutide treatment, compared against placebo. Shah sat down with 

 to discuss the trial and the future of GLP-1 RAs in endocrinology.

Although insulin has long been considered the optimal treatment for T1D, only around 20% of patients achieve adequate glycemic control based on current targets. Weight gain is also a significant concern for patients with T1D on intensive insulin therapy. These patients are also experiencing a rapid increase in obesity prevalence.

GLP-1 RAs have an established safety profile in treating type 2 diabetes and result in hemoglobin A1C reduction, significant weight loss, and a decrease in long-term micro- and macrovascular complications. However, they are not recommended for use in treating T1D by any current guidelines. Past trials analyzing early GLP-1 RAs such as liraglutide found no consistent benefit in A1C reduction or insulin dose reduction. However, these studies do not account for more effective, modern GLP-1 RAs such as semaglutide.

Recently, with GLP-1 RAs rising in popularity in both the commercial and medical settings, many patients have begun to adopt them into treatment plans for T1D. This is an especially attractive option given their history of relieving cardio-renal diseases, which are the leading cause of mortality in T1D. However, these uses are distinctly off-label and contrary to national guidance, as limited research exists examining modern GLP-1 RAs in relation to T1D.

The ADJUST-T1D trial indicated a significant achievement of a composite primary endpoint of a time in range of >70%, time below range of <4%, and a 5% body weight reduction in the semaglutide cohort compared to placebo. This evidence indicates a successful reduction in obesity in patients with T1D.

Although the results indicate grounds for a potential US Food and Drug Administration (FDA) approval submission, sponsor Novo Nordisk has not yet confirmed intentions to do so. In the interview, Shah discusses the potential for the acceptance of these data, despite being positioned outside of the ADA.

“I don’t know whether it will happen or not, the American Diabetes Association standard of care always updates based on the evidence, and this is a level of evidence because it’s a double-blind randomized controlled trial,” Shah told 

. “And so hopefully that might be added into the ADA standard of care.”

Shah also discusses his personal belief regarding T1D treatments, calling for a wider scope to be taken. Insulin has long been the sole focus of T1D medication, and as its returns diminish, Shah believes that more options must be sought out and tested.

“I would just say that I think we spent 100 years on insulin delivery, which is good. It’s now time to think beyond that, and GLPs and future SGLT2s would be a great way to start,” Shah said. “Within the GLP-1 class, we saw at the ADA meeting that there are so many new classes; once monthly, monoclonal antibody, and so on. It’s such an amazing field, and I hope that people with type 1 diabetes could benefit from some of those. They open up an avenue to do a lot of research.”

Resnick O, Bril F, Beauchamp G. Glucagon-like peptide-1 receptor agonists and type 1 diabetes: a potential game changer?. Front Endocrinol (Lausanne). 2025;15:1520313. Published 2025 Jan 21. doi:10.3389/fendo.2024.1520313

Anson M, Zhao SS, Austin P, Ibarburu GH, Malik RA, Alam U. SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study. Diabetologia. 2023;66(10):1869-1881. doi:10.1007/s00125-023-05975-8

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

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Shah discusses the stagnation of the T1D treatment landscape and the potential progress that GLP-1 RA research could present.

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

 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 

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 

“About 100 years from insulin discovery, and we just focused on how to best deliver insulin,” Shah told 

. “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%.

“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; 

 <.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).

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.

“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.

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

Shah discusses the results from the ADJUST-T1D trial comparing semaglutide to placebo, which saw a significant disparity in semaglutide’s favor.

Viral Shah, MD

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