The use of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide and tirzepatide, is rapidly increasing among patients with type 1 diabetes (T1D), despite the absence of FDA approval for this specific use. A recent study published in the Journal of the American Medical Association (JAMA) highlights this trend, raising concerns about potential safety issues and the need for further research.
Increase in GLP-1 Prescriptions
The study, analyzing electronic health record data from nearly 950,000 T1D patients in the Epic Cosmos healthcare database, revealed a significant surge in GLP-1 prescriptions from 2010 to 2023. Specifically, the percentage of T1D patients receiving GLP-1 therapies jumped from 0.3% to 6.6% (p < 0.001). Novo Nordisk’s semaglutide, marketed as Ozempic for type 2 diabetes (T2D) and Wegovy for weight loss, showed the most prominent increase, rising from 0.2% in 2018 to 4.4% in 2023. Eli Lilly’s tirzepatide, approved as Mounjaro for T2D and Zepbound for obesity, was prescribed to 1.3% of T1D patients within a year of its initial approval in 2022.
Off-Label Use and Patient Characteristics
The researchers noted that GLP-1 receptor agonists were most frequently prescribed to T1D patients who also had obesity. This suggests that the off-label use is potentially driven by the weight management benefits associated with these drugs.
SGLT2 Inhibitors
The study also examined the prescription patterns of sodium-glucose cotransporter-2 (SGLT2) inhibitors, another class of medications commonly used in T2D. Similar to GLP-1 agonists, the use of SGLT2 inhibitors in T1D patients increased significantly from 0.1% in 2010 to 2.4% in 2023.
Safety Concerns and Expert Warnings
Corresponding author Hui Shao, from the Emory University Rollins School of Public Health, emphasized the potential safety concerns associated with using GLP-1 and SGLT2 therapies in T1D. "This increase is likely to continue due to their significant benefits in weight management and cardiorenal protection observed in individuals with type 2 diabetes and the general obese population," Shao stated. However, she cautioned that "urgent studies are needed" to better understand the benefits and risks of these drug classes in T1D, and that "caution should be used" when treating T1D patients with these medications due to the risk of ketoacidosis, a serious complication arising from insulin deficiency.
Broader Implications
The increasing off-label use of GLP-1 receptor agonists in T1D occurs against the backdrop of expanding therapeutic applications for these drugs. Wegovy recently received FDA approval to reduce the risk of cardiovascular events in overweight or obese patients with cardiovascular diseases. Additionally, Zepbound is being investigated as a treatment for obstructive sleep apnea. Studies have also suggested potential benefits in conditions such as Alzheimer’s disease, opioid overdose, tobacco use disorder, and cirrhosis in metabolic dysfunction-associated steatotic liver disease.
