GLP-1 Receptor Agonists and Chronic Subdural Hematoma: Novel Evidence for Neuroprotection from a Large Retrospective Cohort Study

Introduction: Chronic subdural hematoma (CSDH) represents a significant neurosurgical condition with increasing prevalence among aging populations, particularly those with comorbidities and on anticoagulation therapy. Recent evidence suggests that inflammation plays a crucial role in the pathogenesis and progression of CSDH. Glucagon-like peptide-1 (GLP-1) receptor agonists, widely used in diabetes management and obesity treatment, have demonstrated notable anti-inflammatory properties in various clinical contexts. However, their potential impact on CSDH outcomes remains unexplored.

Methods: TriNetX, a national research network, was retrospectively queried to identify 147,761 cSDH patients between 2012 and 2022. Of these patients, 1,316 had a prescription for a GLP-1 agonist from 6 months before the diagnosis to the 6 months after the diagnosis of cSDH. 146,625 did not have a prescription for a GLP-1 agonist in the entirety of their medical record that was on the database. One-to-one propensity score matching for age, sex, race, and comorbidities was conducted to balance cohorts. The incidence of in outcomes were then assessed within the one-year postoperative periods.

Results: After propensity score matching, there were 1,316 patients in each cohort. On Kaplan meier survival analysis, the GLP-1 agonist cohort was significantly less likely to have in-hospital mortality (Hazard Ratio (HR): 0.602, and 95% confidence interval (CI): (0.488,0.742)), and cerebral edema (odds Ratio (HR): 0.653, and 95% confidence interval (CI): (0.442,0.965)). The GLP-1 agonist cohort also had less likelihood of developing seizures (0.821, (0.66,1.021)), coma (0.731, (0.489,1.094)), craniotomy for evacuation (0.808, (0.573,1.139)), and brain compression (0.723, (0.515,1.015)), and blindness (0.795, (0.48,1.316)).

Conclusion : In this large-scale retrospective analysis, GLP-1 agonist use was associated with significantly reduced in-hospital mortality and cerebral edema in patients with chronic subdural hematoma. While not reaching statistical significance, there were also promising trends toward reduced neurological complications including seizures, coma, and brain compression. These findings suggest that GLP-1 agonists may have a neuroprotective effect in CSDH patients. Further prospective studies are warranted to validate these findings and explore the potential therapeutic role of GLP-1 agonists in CSDH management.