Beyond Insulin: Evaluating GLP-1 RAs as Adjunctive Therapy in Type 1 Diabetes, With Viral Shah, MD

For decades, management of type 1 diabetes (T1D) has centered almost exclusively on insulin delivery. Even as automated insulin delivery (AID) technology has advanced, a substantial proportion of patients fail to achieve time in range > 70%, driven in part by rising rates of overweight and obesity, which increase insulin resistance and total daily insulin requirements. Insulin alone also does not address cardiovascular risk, which in T1D is 6 to 8 times greater than in people without diabetes.

These limitations have fueled interest in adjunctive pharmacotherapy, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Accumulating data from observational studies and randomized controlled trials point to clinically meaningful improvements in HbA1c, time in range, and weight in T1D patients, without a demonstrated increase in severe hypoglycemia risk. Regulatory trials are now underway, raising the prospect of a formal T1D indication.

At the American Association of Clinical Endocrinology (AACE) 2026 Annual Meeting, Viral Shah, MD, a professor of medicine in the division of endocrinology & metabolism and director of Diabetes Clinical Research at the IU Center for Diabetes and Metabolic diseases at Indiana University, led a session on this topic, drawing on data from the ADJUST-T1D trial, which evaluated semaglutide in people with T1D, alongside other observational and controlled studies.

Across these data sources, HbA1c reductions ranged from approximately 0.4% to 1.0%, translating to time in range improvements of roughly 5% to 10% depending on baseline glycemic status. Weight loss outcomes appeared comparable to those observed in type 2 trials, though Shah noted that head-to-head comparisons have not been conducted.

He emphasized that the clinical benefit of GLP-1 RAs in T1D is inseparable from appropriate insulin titration. Initiating semaglutide at 0.25 mg or tirzepatide at 2.5 mg typically necessitates a 20% to 30% insulin reduction, but the appropriate degree of down-titration depends on baseline HbA1c and time in range.

Patients with an HbA1c of 8.5% to 9% may not require immediate insulin reduction, as the GLP-1 RA effect is needed to bring glycemia down. Conversely, patients already near target require proactive down-titration to avoid hypoglycemia. Shah recommended follow-up within 1 to 2 weeks of initiation and monthly thereafter to monitor and adjust.

Regarding safety, available data have not shown an increased rate of diabetic ketoacidosis (DKA) with GLP-1 RAs in T1D, though Shah noted that longer-duration trials will be needed to definitively characterize this risk. Gastrointestinal tolerability generally mirrors what is seen in type 2 populations, with one important distinction: patients with T1D appear to tolerate lower maximum doses, and clinicians should calibrate titration accordingly using established GI mitigation strategies.

Shah closed with a direct challenge to industry stakeholders, arguing that obesity in T1D deserves the same clinical priority it receives in type 2, and that the field has been too slow to generate the large-scale regulatory evidence needed to make these therapies available to T1D patients.

“Through your platform, I want to say that all industry, I want them not to ignore type 1 space and do something more so that we can utilize those drugs safely in people with type 1 diabetes as well,” Shah concluded

Editors’ note: Shah reports relevant disclosures with Sanofi, Novo Nordisk, Lilly, Dexcom, Insulet, Tandem Diabetes Care, Medtronic, Sequel Med Tech, Abbott Diabetes, Roche, Biomea Fusion, and T1D Scout.

References

1. Kueh MTW, Chew NWS, Al-Ozairi E, et al. The emergence of obesity in type 1 diabetes. Int J Obes 48, 289–301 (2024). https://doi.org/10.1038/s41366-023-01429-8

2. Shah VN, Akturk HK, Kruger D, et al. Semaglutide in Adults with Type 1 Diabetes and Obesity. NEJM. doi:10.1056/EVIDoa2500173

3. Shah VN. Beyond Type 2: Evaluating GLP-1 Use in Type 1 Diabetes and Obesity. Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, April 22-24, 2026.