GLP-1 receptor agonists (GLP-1 RAs) have become among the most prescribed drug classes in modern endocrinology, reshaping the management of type 2 diabetes through benefits extending beyond glycemic control, including cardiovascular risk reduction, renal protection, and weight loss.
However, GLP-1 RAs’ potential role in type 1 diabetes has remained largely uncharted. Despite the growing prevalence of obesity in the type 1 population, estimated at approximately 37% in recent data, GLP-1 RAs currently do not carry a US Food and Drug Administration approval for this indication, and type 1 diabetes was excluded from the pivotal trials underpinning their commercial approval.
Chief among the concerns limiting off-label use has been the potential risk of diabetic ketoacidosis (DKA). In patients with type 1 diabetes, a population who depends entirely on exogenous insulin, there are concerns regarding the appetite-suppressing and gastric-slowing effects of GLP-1 RAs potentially prompting inappropriate reductions in insulin dosing and precipitating ketoacidosis. Pancreatitis has also been raised as a safety signal across the GLP-1 RA class.
However, without dedicated trial data in this population, clinicians prescribing these agents off-label have had little real-world evidence to guide risk counseling. New data presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 begin to address that gap.
Justin Do, DO, an endocrinology fellow at Loma Linda University Medical Center, presented findings from a retrospective, cross-sectional analysis of 7377 adults with type 1 diabetes seen at a single academic center between July 2024 and July 2025. The primary outcome was hospital admission for DKA or pancreatitis based on ICD-10 coding.
Of the included patients, 255 were on a GLP-1 RA, either semaglutide (n = 167), tirzepatide (n = 60), dulaglutide (n = 19), or liraglutide (n = 9). Patients in the GLP-1 RA group were older on average (mean age 45 vs 37 years), had higher mean BMI (33.4 vs 26.6 kg/m²), and were predominantly female (65.2%).
Among GLP-1 RA users, there were 0 admissions for either DKA or pancreatitis during the study period. In the non-GLP-1 group, DKA admission rates were 0.39% and pancreatitis admissions were 0.55%, although investigators noted neither difference reached statistical significance (P = .62 and P = .64, respectively). Overall hospital admission rate was investigated as an exploratory finding of potential clinical relevance, which was significantly lower in GLP-1 RA users compared to non-users (7.45% vs 13.11%l χ²=6.52; P = .01).
However, investigators acknowledged meaningful limitations, including the retrospective, single-center design limiting generalizability and the relatively small GLP-1 RA cohort potentially being underpowered to detect rare events. Additionally, dosing and duration of GLP-1 RA therapy were not captured, and the study relied on ICD-10 coding rather than chart-confirmed diagnoses. Selection bias is also a concern, as patients prescribed GLP-1 RAs off-label may represent a more closely monitored or metabolically managed subset of the type 1 population.
“GLP-1 RA therapy may offer meaningful clinical benefit in adults with type 1 diabetes,” Do and colleagues wrote. “However, further studies are warranted in this population.”
References
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
Do J, Seidel V, Hassan B. Diabetic Ketoacidosis and Safety Outcomes with GLP-1 Agonists in Type 1 Diabetes Mellitus. Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, April 22-24, 2026.
