Impact of GLP-1 Receptor Agonists on Cranial Nerve Palsies in Type 2 Diabetes: A Retrospective Cohort Study

Abstract Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as key agents in managing type 2 diabetes mellitus (T2DM), with proven benefits in glycemic control, weight loss, and cardiovascular risk reduction. However, their neurologic safety profile remains underexplored. Objective: To evaluate the association between GLP-1 receptor agonist use and the incidence of cranial nerve (CN) palsies in patients with T2DM. Methods: This retrospective cohort study utilized the TriNetX Global Collaborative Network, comprising de-identified records from 145 healthcare organizations. Patients with T2DM treated with GLP-1 receptor agonists were compared to matched T2DM controls who never received GLP-1 therapy. Exclusion criteria included prior CN palsy diagnoses, CNS malignancy, type 1 diabetes, and neurological comorbidities. Outcomes assessed over a 10-year period included third nerve palsy (H49.0), sixth nerve palsy (H49.2), and Bell’s palsy (G51.0). Propensity score matching was applied for age, sex, hypertension, obesity, and dyslipidemia. Results: After matching (n=765,345 per group), GLP-1 users had a significantly increased incidence of CN III palsy (RR: 1.63, 95% CI: 1.41–1.87), CN VI palsy (RR: 1.89, 95% CI: 1.68–2.12), and Bell’s palsy (RR: 1.37, 95% CI: 1.30–1.44), with p < 0.001 for all. Hazard ratios and Kaplan-Meier survival analysis corroborated these findings. Conclusion: While absolute risks remain low, GLP-1 receptor agonist use was associated with a statistically significant increase in cranial nerve palsies. These findings underscore the need for additional research into the neurophysiological effects of GLP-1 therapies, particularly in ophthalmological and neurological domains.