Semaglutide improves 90-day functional recovery in acute large vessel occlusion stroke patients after endovascular thrombectomy

Acute large vessel occlusion (LVO) stroke is a severe form of ischemic stroke often requiring rapid reperfusion therapies like endovascular thrombectomy (EVT). While EVT is highly effective, many patients still experience poor functional outcomes due to ongoing neuronal damage or reperfusion injury. Current standard-of-care often includes intravenous thrombolysis (IVT), but a significant portion of patients are ineligible or present beyond the IVT window. There is a critical need for adjunctive neuroprotective agents to enhance recovery. Glucagon-like peptide-1 receptor (GLP-1R) agonists like semaglutide have demonstrated neuroprotective properties in preclinical models, making them promising candidates for this unmet clinical need.

This investigator-initiated, multicenter, prospective, randomized, open-label, blinded endpoint assessment (PROBE) trial (GALLOP-2) was conducted across 19 centers in China. Researchers assigned 390 patients with acute ischemic LVO stroke, presenting within 24 hours of onset and not receiving IVT, to two groups. The semaglutide group (n=195) received 0.5 mg subcutaneous (SC) semaglutide before and 7 days after EVT. The control group (n=195) received EVT alone. The primary efficacy outcome was the ordinal shift of the modified Rankin Scale (mRS) at 90 days, assessing functional recovery. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and death at 90 days.

At 90 days, the semaglutide group demonstrated superior functional outcomes compared to the control group. The common odds ratio for an improved mRS shift was 0.67 (95% confidence interval, 0.47 to 0.96; P=0.029), indicating a statistically significant benefit. Symptomatic intracranial hemorrhage rates were 10.8% in the semaglutide group versus 5.7% in the control group (P=0.073), a numerical increase that did not reach statistical significance. Ninety-day mortality rates were 17.4% in the semaglutide group compared to 14.4% in the control group (P=0.407), also not statistically significant. The study concluded that semaglutide was well-tolerated with no observed harm despite the numerical differences in safety endpoints. This finding builds upon previous GALLOP study results, validating the potential of GLP-1R agonism in acute stroke. > Semaglutide significantly improved 90-day functional recovery in LVO stroke patients post-EVT, with a common odds ratio of 0.67 (P=0.029) for an improved modified Rankin Scale shift.