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

Wang H, Ko H, Leung TW, Huang J, Sai J, Liang Y, Li H, Zhang J, Cao Q, Zang W, Li Y, Ma SH and 34 more

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Lui WT, Choi J, Chan C, Wong J, Kwok AJ, Ma K, Fan F, Chan A, Ip V, Leung H, Soo Y, Wong KT, Lai B, Chu CM, Leung HS, Hui A, Cheung T, Abrigo J, Li SH, Chan L, Yeung J, Pan S, Yip T, Lui LT, Hung T, Tsang SF, Leng X, Lam B, Mok VCT, Chan RHM, Nguyen TN, Hu W, Che F, Ip BY

Nature communications14 Dec 2025Cited by 3 (Europe PMC)

PMID41392086PMCIDPMC12717234DOI10.1038/s41467-025-66167-zPepBankPUB-41392086

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Summary

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).

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialEfficacy outcome
In patients with large vessel occlusion treated by endovascular therapy, semaglutide did not significantly change favorable neurological recovery at 90 days versus standard therapy.
In plain wordsIn patients with a blocked large brain artery, semaglutide did not change recovery at 90 days compared with standard therapy.
Peptide
Semaglutide
Outcome
No significant changeFavorable neurological recovery (mRS 0-2 at 90 days)
Study
n = 140
Comparator
Standard therapy
Analysis
Primary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
0.5 mg · subcutaneous · before and 1 week after EVTAs given in this study (human).
Measurements
Favorable recovery
56.5%
semaglutide
Favorable recovery
54.9%
standard therapy
adjusted RR
1.05 ratio
overall
Source sentences
Summary
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).
3 context sentences(design, population, supporting numbers)
Summary · context
Between August 2023 and July 2024, 140 patients were randomized to semaglutide (n = 69) or standard therapy (n = 71).
Summary · context
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.
Summary · context
Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy.
Show in the study text Report a problemFND-4139208601
02HumanRandomized controlled trialEfficacy outcome
In patients with large vessel occlusion not given intravenous thrombolysis, semaglutide increased favorable neurological recovery versus standard therapy in an exploratory analysis.
In plain wordsIn an exploratory analysis of patients with a blocked brain artery and no clot-busting drugs, more recovered well with semaglutide than with standard therapy.
Peptide
Semaglutide
Outcome
IncreaseFavorable recovery in the no-IVT stratum
Study
n = 68
Comparator
Standard therapy
Analysis
Exploratory
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
0.5 mg · subcutaneous · before and 1 week after EVTAs given in this study (human).
Measurements
Favorable recovery
64.7%
semaglutide, no IVT
Favorable recovery
44.1%
standard therapy, no IVT
adjusted RR
1.18 ratio
no-IVT stratum
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy.
Show in the study text Report a problemFND-4139208602
03HumanRandomized controlled trialEfficacy outcome
In patients with large vessel occlusion given intravenous thrombolysis, favorable neurological recovery was similar with semaglutide and standard therapy.
In plain wordsIn patients with a blocked large brain artery who got clot-busting drugs, recovery was similar with semaglutide and standard therapy.
Peptide
Semaglutide
Outcome
No significant changeFavorable recovery in the IVT stratum
Study
n: not reported in source
Comparator
Standard therapy
Analysis
Exploratory
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
0.5 mg · subcutaneous · before and 1 week after EVTAs given in this study (human).
Source sentences
Summary
The primary outcome was similar between two groups in the IVT-stratum.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy.
Show in the study text Report a problemFND-4139208603
04HumanRandomized controlled trialSafety outcome
In patients with large vessel occlusion, no severe adverse event was attributed to semaglutide.
In plain wordsIn patients with a blocked large brain artery, no severe side effect was linked to semaglutide.
Peptide
Semaglutide
Outcome
No significant changeSevere adverse events attributed to semaglutide
Study
n = 69
Comparator
Standard therapy
Outcome group
Adverse events · Nervous system and cognition
Studied dose
0.5 mg · subcutaneous · before and 1 week after EVTAs given in this study (human).
Source sentences
Summary
No severe adverse event was attributed to semaglutide treatment.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy.
Show in the study text Report a problemFND-4139208605
05HumanRandomized controlled trialEfficacy outcome
In patients with large vessel occlusion, the effect of semaglutide on recovery differed by intravenous thrombolysis status (interaction P = 0.02).
In plain wordsIn patients with a blocked large brain artery, the effect of semaglutide on recovery depended on whether they also got clot-busting drugs.
Peptide
Semaglutide
Outcome
MixedTreatment effect modification by IVT
Study
n: not reported in source
Comparator
Standard therapy
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
0.5 mg · subcutaneous · before and 1 week after EVTAs given in this study (human).
Source sentences
Summary
We observed treatment effect modification by intravenous thrombolysis (IVT) on semaglutide therapy (p_interaction = 0.02)
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
Patients were randomized to semaglutide therapy (0.5 mg subcutaneous semaglutide before and 1 week after EVT) or standard therapy.
Show in the study text Report a problemFND-4139208604

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 1 not yet recruiting · 1 completed · source ClinicalTrials.gov (opens in a new tab)

Not yet recruitingPhase 2/3NCT07734792

Tirzepatide in Thrombectomy-Treated Acute Ischemic Stroke: A Randomized Trial

yifang zhun = 726est. 20 Sept 2026 to est. 31 Jul 2028

Acute Ischemic Stroke (AIS)

Trial page ClinicalTrials.govUpdated 1 Oct 2026

CompletedPhase 2NCT05920889

Glucagon-like Peptide 1 Receptor Agonist in Acute Large Vessel Occlusion Stroke Treated by Reperfusion Therapies

Chinese University of Hong Kongn = 1401 Aug 2023 to 25 Oct 2024

Stroke · Stroke, Acute · Stroke, Ischemic · Brain Diseases

Trial page ClinicalTrials.govUpdated 7 Mar 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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