Outcomes of GLP-1 receptor agonist use following ischemic stroke: a propensity score-matched real-world analysis

Glucagon-like peptide-1 receptor agonists (GLP-1As) have been shown to be beneficial in primary stroke prevention for high-risk patients. However, their benefits following major ischemic events are unclear. Herein, we present real-world analysis assessing outcomes of GLP-1A following major ischemic event.

This retrospective cohort study utilized the TriNetX platform. Adults (≥ 18 years) with AIS treated with intravenous thrombolysis (IVT) were identified; exposure was any US FDA-approved GLP-1A initiated within 6 months of the index stroke. The comparator was IVT-treated patients without GLP-1A exposure. Outcomes assessed at 5 years included major adverse health-care events (MAHEs): number of emergency department (ED) visits and inpatient hospitalizations, and all-cause mortality. One-to-one propensity score matching balanced baseline characteristics. We estimated risk difference/risk ratio/odds ratio, 5-year Kaplan-Meier (KM) event probabilities with log-rank tests, and Cox hazard ratios (HRs) with 95% CIs; small cells (≤ 10) were masked per data-use agreement.

Of 69,005 eligible patients, 549 received GLP-1A and 68,938 did not; after matching, 432 per group were analyzed. GLP-1A exposure was associated with lower all-cause mortality (7.4% vs 14.1%; HR 0.61, 95% CI 0.39-0.93), lower ED visits (37% vs 47%; HR 0.78, 95% CI 0.63-0.95), and lower inpatient hospitalizations (31.9% vs 45.4%; HR 0.69, 95% CI 0.55-0.85); KM log-rank p ≤ 0.05 for all. Median time to first MAHE was longer with GLP-1A (1293 vs 897 days for hospitalization and 886 vs 603 days for ED visits).

GLP-1A therapy after IVT is associated with favorable long-term safety and utilization signals and warrants confirmation in a prospective study with standardized initiation.