Abstract
<title>Abstract</title> <p> Background Venous sinus stenting (VSS) effectively resolves mechanical outflow obstruction in idiopathic intracranial hypertension (IIH), yet recurrence remains a non-negligible risk. Metabolic drivers, particularly obesity, may undermine long-term success. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide offer potent weight loss and potential cerebrospinal fluid modulation, but their role in post-stenting management is unestablished. We investigated whether baseline body mass index (BMI) predicts IH recurrence following VSS and whether adjunctive semaglutide reduces recurrence risk in a non-randomized exploratory cohort. Methods We conducted a two-phase cohort study. Phase 1 retrospectively analyzed 50 IIH patients with transverse sinus stenosis (TSS) undergoing VSS (2018–2023) to identify recurrence predictors. Phase 2 prospectively assigned 34 IIH patients (2024–2025) to semaglutide (n = 17) or standard care (n = 17). The primary outcome was intracranial hypertension (IH) recurrence (lumbar puncture opening pressure ≥ 250 mmH₂O) at 16 weeks. Secondary outcomes included pressure metrics, weight change, symptom scores, and optic measures. Results In Phase 1, higher baseline body mass index (BMI) (OR 1.206, 95% CI 1.008–1.444, <italic>P</italic> = 0.041) independently predicted intracranial hypertension (IH) recurrence after VSS. In Phase 2, semaglutide significantly reduced IH recurrence compared to controls (5.9% vs 35.3%, <italic>P</italic> = 0.034). Semaglutide also lowered follow-up opening pressure (205.29 vs 249.71 mmH₂O, <italic>P</italic> = 0.007), reduced BMI (median ΔBMI − 4.00 vs 0.00 kg/m², P < 0.001), a lower rate of persistent papilledema (17.6% vs 52.9%; <italic>P</italic> = 0.031), and alleviated tinnitus (median ΔTFI − 15.40 vs 0.00, P = 0.040). Adverse events were mild-to-moderate gastrointestinal symptoms. Conclusion In this cohort, higher baseline BMI was identified as a risk factor for IH recurrence after VSS in IIH. Adjunctive semaglutide therapy was associated with a lower recurrence rate ang greater weight loss, supporting its integration into post-stenting metabolic management. Given the exploratory design and small sample size, all findings are hypothesis-generating and require confirmation in larger randomized trials. Trial registration: NCT06361823. Registered on March 2, 2024, by Xuanwu Hospital, Capital Medical University. </p>