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

H Hao Wang (Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA) H Ho Ko T Thomas W. Leung (Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong) J Junzhe Huang J Junjie Sai Y Yu Liang (The Sixth Laboratory) H Haipeng Li J Jie Zhang Q Qingyang Cao W Wentao Zang Y Yinfei Li S Sze Ho Ma W Wai Ting Lui J Joseph Choi C Charlie Chan J Jason Wong A Andrew J. Kwok K Karen Ma F Florence Fan A Anne Chan V Vincent Ip H Howan Leung Y Yannie Soo K Ka Tak Wong B Billy Lai C CM Chu H Ho Sang Leung A Anselm Hui T Tom Cheung J Jill Abrigo S Siu Hung Li L Larry Chan J Jonas Yeung S Sangqi Pan T Terry Yip L LT Lui T Trista Hung S Suk Fung Tsang X Xinyi Leng B Bonnie Lam V Vincent C. T. Mok (Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong) R Rosa H. M. Chan T Thanh N. Nguyen (Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston) W Wei Hu F Fengyuan Che B Bonaventure Y. Ip

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).

Article Details

Volume / Issue Vol. 16, Issue 1
Published December 14, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (46)

H

Hao Wang

Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA

H

Ho Ko

T

Thomas W. Leung

Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong

J

Junzhe Huang

J

Junjie Sai

Y

Yu Liang

The Sixth Laboratory

H

Haipeng Li

J

Jie Zhang

Q

Qingyang Cao

W

Wentao Zang

Y

Yinfei Li

S

Sze Ho Ma

W

Wai Ting Lui

J

Joseph Choi

C

Charlie Chan

J

Jason Wong

A

Andrew J. Kwok

K

Karen Ma

F

Florence Fan

A

Anne Chan

V

Vincent Ip

H

Howan Leung

Y

Yannie Soo

K

Ka Tak Wong

B

Billy Lai

C

CM Chu

H

Ho Sang Leung

A

Anselm Hui

T

Tom Cheung

J

Jill Abrigo

S

Siu Hung Li

L

Larry Chan

J

Jonas Yeung

S

Sangqi Pan

T

Terry Yip

L

LT Lui

T

Trista Hung

S

Suk Fung Tsang

X

Xinyi Leng

B

Bonnie Lam

V

Vincent C. T. Mok

Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong

R

Rosa H. M. Chan

T

Thanh N. Nguyen

Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston

W

Wei Hu

F

Fengyuan Che

B

Bonaventure Y. Ip