Abstract
IMPORTANCE: Glucagon-like peptide-1 receptor agonists can reduce the risk of cardiovascular events in patients with high-risk type 2 diabetes (T2D). However, dedicated randomized clinical trials that evaluate their efficacy in acute ischemic stroke are lacking. OBJECTIVE: To investigate the safety and efficacy of liraglutide in patients with T2D and minor acute ischemic stroke (AIS) or high-risk transient ischemic attack (TIA). DESIGN, SETTING, AND PARTICIPANTS: The LAMP trial was designed as a multicenter, controlled, prospective, randomized, open-label, blinded end point trial and conducted at 27 hospitals in China from June 25, 2019, through December 27, 2023. The final follow-up was on March 24, 2024. Data were analyzed on May 1, 2024. The study included patients with T2D who had minor AIS (National Institutes of Health Stroke Scale score ≤3) or high-risk TIA (ABCD2 score [age, blood pressure elevation on first assessment after TIA, unilateral weakness, speech disturbance, duration of symptoms and diabetes] ≥4). INTERVENTIONS: Eligible patients were randomized within 24 hours of symptom onset to the liraglutide group and the control group. Both groups received standard treatment according to the guidelines. The liraglutide group received liraglutide once daily for 90 days (0.6 mg for the first week, which was increased to 1.2 mg in the second week and followed by 1.8 mg until day 90) in addition to standard therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was stroke recurrence (ischemic or hemorrhagic) after 90 days, and the safety outcome was symptomatic intracranial hemorrhage and all-cause mortality at 90 days. RESULTS: In all, 636 patients (median [IQR] age, 63.5 [57.8-70.0] years; 231 female individuals [36.3%]) were randomized. Within 90 days, 25 patients (7.9%) in the liraglutide group and 44 (13.8%) in the control group experienced stroke recurrence (hazard ratio, 0.56; 95% CI, 0.34-0.91; P = .02). A significantly higher proportion of patients (modified Rankin Scale score, ≤1) in the liraglutide group (274 [87.3%]) than in the control group (246 [77.8%]) achieved excellent functional outcomes (odds ratio, 1.95; 95% CI, 1.28-3.00; P = .002). The rates of symptomatic intracranial hemorrhage and all-cause mortality were low and similar between the groups. CONCLUSIONS AND RELEVANCE: The trial results suggest that among Chinese patients with T2D and minor AIS or high-risk TIA, liraglutide treatment might reduce stroke recurrence and improve 90-day outcomes. However, given the underpowered nature of the study, these findings should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03948347.