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

Inclusion Criteria: Participants must meet all of the following criteria: 1. Age \>18 years and ≤80 years; 2. Acute ischemic stroke with imaging-confirmed anterior large vessel occlusion at: * Terminal ICA, * M1 segment of the middle cerebral artery, or * Dominant M2 segment; 3. NIHSS score between 6 and 25 prior to randomization; 4. Alberta Stroke Program Early CT Score (ASPECTS) of 6-10 before randomization; 5. Time from symptom onset (or last known well) to planned endovascular thrombectomy within 24 hours; 6. Pre-stroke mRS score of 0-1; 7. Patients presenting within 6 hours of symptom onset are eligible for direct EVT. Patients presenting between 6 and 24 hours after symptom onset must undergo advanced imaging demonstrating a salvageable perfusion mismatch and meet the DEFUSE-3 criteria: an infarct core volume \<70 mL, a mismatch volume \>15 mL, and a mismatch ratio \>1.8; 8. Written informed consent provided by the participant or a legally authorized representative. Exclusion Criteria: Participants meeting any of the following criteria will be excluded: 1. Posterior-circulation large vessel occlusion stroke; 2. Receipt of intravenous thrombolysis prior to randomization; 3. Simultaneous bilateral anterior-circulation occlusions or concurrent anterior- and posterior-circulation occlusions; 4. Intracranial hemorrhage on baseline CT or MRI, including subarachnoid hemorrhage or intracerebral hemorrhage; evidence of large established infarction, defined as: * ASPECTS \<6, * Ischemic core volume ≥70 mL on CTP, or * Infarction involving \>1/3 of the middle cerebral artery territory; 5. Active bleeding within the previous month (e.g., gastrointestinal, genitourinary, or retinal hemorrhage), major organ surgery or biopsy within 14 days before stroke onset, or known bleeding diathesis; 6. Refractory hypertension despite treatment, defined as persistent systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg; 7. Severe hepatic or renal impairment, including: * Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m², * Serum creatinine \>200 μmol/L, * Child-Pugh Class C or higher liver disease, * Recurrent unexplained hypoglycemia; 8. Blood glucose \<2.7 mmol/L or \>22.2 mmol/L; platelet count \<80 × 10⁹/L; or international normalized ratio (INR) \>1.7; 9. Previous use of GLP-1 receptor agonists or GIP receptor agonists, or known hypersensitivity to these agents; 10. Personal or family history of medullary thyroid carcinoma (MTC) or diagnosis of Multiple Endocrine Neoplasia Type 2 (MEN2); 11. History of severe anxiety or depression prior to stroke onset; 12. Severe underlying disease with life expectancy \<1 year, such as advanced malignancy; 13. Pregnancy or breastfeeding; 14. Participation in another clinical trial.