Glucagon-Like Peptide-1 Receptor Agonists and Risk of Nontraumatic Intracerebral Hemorrhage in Patients With Type 2 Diabetes

BACKGROUND: GLP-1RAs (glucagon-like peptide-1 receptor agonists) have consistently demonstrated a protective effect against ischemic stroke. However, whether this benefit also extends to nontraumatic intracerebral hemorrhage (ICH) remains unknown. Given the blood pressure–lowering and anti-inflammatory properties of GLP-1RAs, we aimed to evaluate their potential impact on ICH risk in patients with type 2 diabetes. METHODS: We conducted a retrospective cohort study using global health care data from the TriNetX network. Patients with type 2 diabetes who used GLP-1RAs (n=326 777) were compared with those who did not (n=643 614). Propensity score matching (1:1) was performed to balance baseline characteristics, and follow-up was conducted for up to 4 years. The primary outcomes included all-cause mortality, ischemic stroke, and ICH (overall and by location). Hazard ratios and 95% CIs were calculated to assess the mean treatment effect in the treated group. RESULTS: After propensity score matching (resulting in 2 balanced groups of 255 460 individuals each), GLP-1RAs use was associated with a lower risk of ICH (hazard ratio, 0.743 [95% CI, 0.684–0.807]). The lower ICH risk associated with GLP-1RAs was observed across all ICH locations (all P ≤0.01). In addition, exposure to GLP-1RAs was associated with a significantly lower rate of mortality (hazard ratio, 0.525 [95% CI, 0.512–0.538]) and ischemic stroke (hazard ratio, 0.871 [95% CI, 0.843–0.901]). CONCLUSIONS: This study highlights a novel potential association between GLP-1RAs and a lower risk of ICH in patients with type 2 diabetes. Prospective trials are needed to confirm the potential protective effect of GLP-1RAs on small vessel rupture.