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 160 healthcare organizations. Patients with T2DM treated with GLP-1 receptor agonists were compared to propensity-score-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, dyslipidemia, insulin exposure, metformin use, and SGL2 inhibitor use.
RESULTS: After matching (n = 841,219 per group), GLP-1 users had a significantly reduced incidence of CN III palsy (RR: 0.86, 95% CI: 0.76-0.98) and Bell's palsy (RR: 0.92, 95% CI: 0.87-0.96), with p < 0.05 for both. CN VI palsy demonstrated a moderately elevated risk ratio (RR: 1.15, 95% CI: 1.03-1.28), but long-term hazard favored GLP-1 therapy (HR: 0.76, 95% CI: 0.68-0.84). Hazard ratios showed consistent protective ratios across all three outcomes, supported by Kaplan-Meier survival analysis (log-rank p < 0.001).
CONCLUSION: While absolute risks remain low, GLP-1 receptor agonist use was associated with a statistically significant decrease in cranial nerve palsies, demonstrating a potential protective pattern across multiple cranial nerve palsies. These findings suggest possible neuroprotective or microvascular benefits of GLP-1 signaling and warrant further investigation, particularly in ophthalmological and neurological domains.
