The CUHK “bench-to-bedside” team (from left): Dr Ho Ko, Prof Thomas Wai-Hong Leung and Dr Bonaventure Yiu-Ming IpResearchers from the Chinese University of Hong Kong (CUHK) and the Gerald Choa Neuroscience Institute (GCNI) have achieved a breakthrough “bench-to-bedside” advancement, translating discovery of multi-omic ageing counteraction with glucagon-like peptide-1 (GLP-1) receptor agonism into a potential new treatment strategy for stroke.
Earlier laboratory findings by the research team, led by Dr Ho Ko of CUHK and GCNI, showed that enhancing GLP-1 signalling can counteract key hallmarks of ageing across multiple organ systems, including the brain. Building on these findings and another previous research on the effect of GLP-1 receptor agonists (RAs) on cerebrovascular protection, they conducted the world’s first phase II randomized clinical trial to evaluate GLP-1 RAs in patients undergoing reperfusion therapy for severe ischaemic stroke caused by large vessel occlusion (LVO). [Cell Metab 2025;37:2362-2380; Commun Biol 2021;4:656; Nat Commun 2025;16:11274]
The trial, conducted between August 2023 and July 2024, included 140 patients with disabling LVO stroke who underwent thrombectomy (+/- intravenous thrombolysis [IVT]) at the Prince of Wales Hospital and a stroke centre in mainland China. Patients were randomized to receive either the GLP-1 RA semaglutide (0.5 mg subcutaneously before puncture, and 1 week after thrombectomy) in addition to standard therapy, or standard therapy alone (ie, thrombectomy +/- IVT).
Good functional recovery at 90 days (primary outcome) was achieved by 56.5 percent of patients who received semaglutide and 54.9 percent of those who received standard therapy, indicating comparable efficacy between the two. Exploratory analyses suggested a potential benefit in patients who did not receive IVT before thrombectomy, with a higher proportion of patients treated with semaglutide vs standard therapy alone achieving favourable neurological recovery (64.7 vs 44.1 percent; pinteraction = 0.02). Achievement of the primary outcome was similar between the two groups in those who received IVT.
No severe adverse events were attributed to semaglutide treatment. Key safety outcomes, including death, malignant brain oedema and intracranial haemorrhage, were similar between the two groups. These findings indicate that semaglutide is safe and well-tolerated in acute stroke patients.
“While endovascular thrombectomy is highly effective at reopening blocked vessels, many patients still experience significant disability due to reperfusion injury and delayed treatment. This highlights the urgent need for adjunct neuroprotective therapies that can protect vulnerable brain tissue during and after treatment to maximize efficacy,” noted Professor Thomas Wai-Hong Leung of the Department of Medicine and Therapeutics, CUHK.
“These findings provide early clinical evidence supporting the safety of GLP-1 RAs in acute stroke setting. They also suggest potential benefits in selected patient groups and pave the way for a larger, phase III randomized trial to confirm the drug’s neuroprotective potential,” concluded leader of the study, Dr Bonaventure Yiu-Ming Ip from the Department of Medicine and Therapeutics, CUHK.