GLP-1 Receptor Agonists and Long-Term Survival after Spontaneous Intracerebral Hemorrhage in Type 2 Diabetes.

Abstract

Survivors of spontaneous intracerebral hemorrhage (sICH) experience substantial long-term mortality, particularly among those with type 2 diabetes mellitus (T2DM). Evidence to guide post-sICH metabolic management remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiometabolic risk profiles and reduce major adverse cardiovascular events in patients with T2DM; however, their association with long-term outcomes after sICH has not been well characterized. We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with T2DM who experienced sICH between 2018 and 2024 were identified. Patients who received a GLP-1 RA within 6 months after sICH were compared with matched controls without GLP-1 RA exposure. Propensity score matching (1:1) was performed using demographic, clinical and pharmacologic variables. The primary outcome was all-cause mortality at 2 and 5 years. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After propensity score matching, 2710 patients were included in each cohort with balanced baseline characteristics. At 2 years, all-cause mortality was lower among GLP-1 RA users than controls (6.5% vs. 7.6%; 0.77 (0.63-0.95)). This association persisted at 5 years (11.2% vs. 13.1%; 0.77 (0.66-0.90)). The study did not assess recurrent intracerebral hemorrhage or cause-specific mortality. In this large real-world cohort of sICH survivors with T2DM, post-hemorrhage GLP-1 RA use was associated with lower long-term all-cause mortality. Given the observational design, causality cannot be inferred. These findings provide hypothesis-generating evidence supporting further prospective studies to clarify the role of GLP-1 RAs in post-sICH secondary prevention.