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December 14, 2025Nature Communications2 citationsOpen Access

Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy—a phase 2 randomized trial

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HWHao WangHKHo KoTLThomas Leung

Key Points

  • The study aimed to assess the effect of semaglutide on neurological recovery in patients with large vessel occlusion receiving endovascular therapy.
  • Phase 2 randomized trial conducted in multiple centers in China
  • Patients with disabling large vessel occlusion were recruited for treatment
  • Participants received either semaglutide or standard therapy and outcomes were measured at 90 days
  • 39 (56.5%) in the semaglutide group achieved favorable neurological recovery versus 39 (54.9%) in the standard therapy group
  • Exploratory analyses showed improved outcomes in patients not receiving thrombolysis
  • No severe adverse events attributed to semaglutide treatment

Abstract

Abstract We aimed to determine the effect of semaglutide on patients with acute large vessel occlusion (LVO) receiving endovascular therapy (EVT). In this phase 2, investigator-initiated, multicenter, prospective, randomized, open-label, blinded endpoint trial conducted in China, we recruited patients with disabling LVO undergoing EVT. Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy. The primary outcome was defined as favorable neurological recovery (modified Rankin Scale 0–2 at 90 days). Between August 2023 and July 2024, 140 patients were randomized to semaglutide ( n = 69) or standard therapy ( n = 71). The primary outcome occurred in 39 (56.5%) in the semaglutide group and 39 (54.9%) in the standard therapy group (adjusted RR 1.05, 95% CI 0.95–1.15, p = 0.37). We observed treatment effect modification by intravenous thrombolysis (IVT) on semaglutide therapy ( p interaction = 0.02); thus we performed the following exploratory analyses: The primary outcome occurred in 22 (64.7%) in the semaglutide group and 15 (44.1%) in the standard therapy group (adjusted RR 1.18, 95% CI 1.02–1.36) in the no-IVT stratum ( n = 68). The primary outcome was similar between two groups in the IVT-stratum. No severe adverse event was attributed to semaglutide treatment. This phase 2 trial suggested semaglutide was safe in patients with LVO and was associated with an improved neurological outcome in patients not receiving IVT. These preliminary observations should be confirmed in a phase 3 randomized trial (ClinicalTrials.gov Identifier: NCT05920889).

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Cite This Study

Wang et al. (2025) studied this question.

synapsesocial.com/papers/6941aaa70f5af7fd17df4adbhttps://doi.org/10.1038/s41467-025-66167-z
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