Glucagon-Like Peptide-1 Receptor Agonist in Large Vessel Occlusion Treated by Reperfusion Therapy: A Phase 2 Randomized Trial

We aimed to determine the effect of semaglutide in patients with acute large vessel occlusion (LVO) receiving endovascular therapy (EVT). In this phase 2, investigator-initiated, multi-center, prospective, randomized, open-label, blinded endpoint trial conducted in China, we recruited patients with disabling LVO undergoing EVT. Patients were randomized (1:1) to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy. The primary efficacy outcome was favorable neurological recovery (modified Rankin Scale 0 to 2 at 90 days). The primary safety outcome was a composite of death, malignant brain edema, and intracranial hemorrhage. 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). The primary safety outcome occurred in 16 (23.2%) in the semaglutide group and 17 (23.9%) in the standard therapy group (adjusted RR 0.99 [95%CI: 0.89, 1.11], p=0.89). We observed treatment effect modification by intravenous thrombolysis (IVT) on semaglutide therapy (pinteraction=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], p=0.02) in the no-IVT stratum (n=68). Outcomes were similar between two groups in the IVT-stratum. This trial suggested semaglutide was safe in patients with LVO and may improve neurological outcome in patients not receiving IVT. These observations should be confirmed in a phase 3 randomized trial ( NCT05920889 ).