Study Investigates Semaglutide Treatment for Large Vessel Occlusion Stroke With and Without IV Thrombolysis

Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide did not significantly improve functional recovery overall in people with acute large vessel occlusion (LVO) stroke undergoing reperfusion therapy but was associated with reduced intracranial hemorrhage (ICH) risk and improved neurologic outcomes in a prespecified subgroup. These results from the phase 2 GALLOP clinical trial (NCT05920889), which evaluated semaglutide administered before and after endovascular thrombectomy, were published in Nature Communications.

The investigator-initiated, multicenter, prospective trial used a randomized, open-label, blinded-end point (PROBE) design and included adults with disabling anterior-circulation LVO treated with endovascular therapy with or without intravenous thrombolysis (IVT). Conducted at 2 thrombectomy centers in China with referrals from 10 additional centers, the study randomized 140 participants to receive subcutaneous semaglutide (0.5 mg before and 1 week after thrombectomy; n=69) or standard therapy (n=71). The primary efficacy end point was favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 2 at 90 days. Secondary outcomes included hemorrhagic complications, infarct size, neurologic change, and mortality.

Key findings from the trial include the following:

• In the overall intention-to-treat population, the primary efficacy end point was not met: functional independence (mRS score of 0 to 2 at 90 days) was achieved by 56.5% of individuals in the semaglutide group and 54.9% of those in the standard therapy group (adjusted risk ratio [RR], 1.05; 95% CI, 0.95 to 1.15; P=.37).
• Semaglutide treatment was associated with a lower incidence of ICH compared with standard therapy (5.8% vs 15.5%; Adjusted RR, 0.91; 95% CI, 0.83 to 0.99), including fewer cases of symptomatic ICH (1.4% for semaglutide vs 9.9% for standard therapy).
• A higher proportion of participants treated with semaglutide vs standard therapy achieved favorable functional outcomes defined as mRS scores of 0 to 1 at 90 days (39.1% vs 29.6%; adjusted RR, 1.18; 95% CI, 1.01 to 1.37).
• Among the subgroup of participants who did not receive IVT (n=68), semaglutide treatment was associated with improved functional outcomes, with 64.7% achieving mRS 0 to 2 at 90 days compared with 44.1% in the standard therapy group (adjusted RR, 1.18; 95% CI, 1.02 to 1.36).
• Individuals in the semaglutide group experienced greater early neurologic improvement, with a median reduction in National Institutes of Health (NIH) Stroke Scale score of -8 points at day 3 vs -5 points in the standard therapy group.
• Rates of death at 90 days were similar between treatment groups (15.9% with semaglutide vs 15.4% with standard therapy), and no cases of hypoglycemia were reported in either group.

Source: Wang, H., Ko, H., Leung, T.W. et al. Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy—a phase 2 randomized trial. Nat Commun 16, 11274 (2025). https://doi.org/10.1038/s41467-025-66167-z