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

New data from the American Diabetes Association’s 85th 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 HCPLive 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.1

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.1

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.3

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.3

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 HCPLive. “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.”

References

1. 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

2. 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

3. 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