Can Semaglutide help reduce the damage caused by a stroke? ASSET trial is a national, multicenter, clinical trial, investigating the safety and efficacy of Semaglutide in non-diabetic patients with acute ischemic stroke.

Stroke is a worldwide leading cause of long-term disability and death. In the most common type of stroke (ischemic stroke), a blood clot obstructs an artery in the brain, and thereby prevents oxygenated blood from reaching an area of the brain. Brain cells are particularly vulnerable to the lack of oxygen. In the areas most severely affected by a stroke, brain cells die after 5 minutes. As more time pass, the affected area expands, and more brain cells perish. Today, efficient treatments aiming at reestablishing the flow of blood by either breaking down the blood clot (thrombolysis) or removing the clot (thrombektomi) are used. However, a significant amount of patients undergoing succesful treamtent, still suffer permanent disability following an ischemic stroke.

Semaglutide mimics a naturally occurring hormone (glucagon-like peptide-1) and is currently used to treat diabetes and obesity. However, semaglutide has also been shown to possess neuroprotective abilities in recent animal studies, where it reduced the damage caused by ischemic stroke in rats. This study sets out to investigate if it's possible to utilize Semaglutide, to increase the resilience of brain cells in patients with an acute ischemic stroke, with the aim of bettering their outcome.

The participants consist of non-diabetic patients with acute ischemic stroke, who will be randomized to:

• Treatment with subcutaneous Semaglutide, or
• No additional treatment (control group)

Both groups will be treated according to the standard national guidelies for acute ischemic stroke.

The two groups will then be compared to see, if patients in the group treated with Semaglutide are less impacted by their stroke.

For detailed project description, please refer to the full trial information at the Clinical Trials Information System (see 'More information' below for link).

Inclusion Criteria:

• Male and female patients (≥ 18 years) at the time of signed informed consent/proxy consent
• Acute ischemic stroke with disabling neurological deficits (defined as an impairment of one or more of the following: language, motor function, cognition, gaze, vision, neglect, or ataxia)
• Onset/last seen well to randomization < 4.5 hours
• None to moderate disability in daily living before symptom onset (pre-stroke modified Rankin Scale 0-3)

Exclusion Criteria:

• Diabetes (known) or plasma/point of care test-glucose >11.1 mmol/L at admission
• BMI< 22
• History of pancreatitis, medullary thyroid carcinoma
• Predisposition or known Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Short remaining life expectancy (< 12months) and/or severe neurodegenerative disease
• Pregnancy or planned pregnancy within 12 months or breastfeeding
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of <30 mL/min/1.73 m2