GLP-1 RAs Improve End-Organ Complications in Patients With Type 1 Diabetes

In patients with type 1 diabetes mellitus (T1DM), the use of GLP-1 receptor agonists was associated with a statistically significant reduction in the risk of several end-organ complications, according to a retrospective cohort analysis.1

Although GLP-1 RAs are well-studied in type 2 diabetes (T2D) and obesity, their effects on patients with T1D have not been substantially explored. Recent research has demonstrated GLP-1s’ efficacy in conjunction with automatic insulin delivery systems, showing substantial improvements in time in range. However, the broader effects of this medication class, including its effects on many end-organ complications such as diabetic retinopathy and renal disease, are not well-known and do not possess significant evidence to support an indication.2

Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, by Christie Polycarpe, DO, department of internal medicine, Jefferson Einstein Medical Center, the present data emphasize the rapidly growing safety data supporting the use of GLP-1s in T1D.1

“Emerging evidence suggests GLP-1 RAs may protect patients with T2DM from end-organ complications, such as major cardiac events and CKD,” Polycarpe and colleagues wrote. “The potential of GLP-1 RAs to help prevent these complications in T1DM remains understudied, likely because insulin is central to T1DM management.”1

Polycarpe and colleagues collected data from the TriNetX Global Collaborative Network, establishing 2 primary cohorts: patients with T1DM who had received GLP-1 RAs (Cohort 1: n = 133,782) and those who had not (Cohort 2: n = 985,724). Propensity score matching for vital signs, body mass index, and bloodwork ultimately narrowed the cohorts to 130,453 patients each. The study’s primary outcomes were renal disease, diabetic retinopathy, diabetic neuropathy, and atherosclerotic disease.1

The team ultimately found that the use of GLP-1 RAs in patients with T1DM was associated with a small but statistically significant reduction in the risk of all 4 outcomes compared to those who did not receive treatment. However, patients who did not receive GLP-1 RAs showed a small but significantly lower risk of atherosclerotic disease. Polycarpe and colleagues acknowledge that this could be a result of temporal bias, wherein patients receiving GLP-1 RAs could potentially have pre-existing cardiovascular disease risk and are receiving the medication for cardiovascular benefit in addition to diabetes.1

Investigators also highlighted several potential mechanisms behind this protective effect, including direct anti-inflammatory actions on micro- and macrovasculature, improved glycemic control, reducing exogenous insulin needs, thereby decreasing glycemic variability and endothelial stress, and reduced visceral adipose tissue, which could lower vascular inflammation indirectly.1

Polycarpe and colleagues also noted limitations inherent in their study’s design, including the risk of inaccuracies in ICD coding, a lack of matching for socioeconomic factors that could confound the results, and the inability to verify duration or adherence to GLP-1 RA treatment after prescription. To that end, the team calls for further research.1

“Further prospective studies and clinical trials are needed to validate our findings,” Polycarpe and colleagues wrote.1

References

1. Polycarpe C, Gadalla K, Rodriguez A. Impact of GLP-1 Receptor Agonists on End-Organ Complications in Type 1 Diabetes: A Retrospective Cohort Analysis. Abstract presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.

2. Shah VN, Akturk HK, Kruger D, et al. Semaglutide in Adults with Type 1 Diabetes and Obesity. NEJM Evid. 2025;4(8):EVIDoa2500173. doi:10.1056/EVIDoa2500173