Glucagon-Like Peptide-1 Receptor Agonists and Outcomes After Intracerebral Hemorrhage in Patients With Type 2 Diabetes: A Propensity-Matched Cohort Study

BACKGROUND AND OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown neuroprotective and anti-inflammatory effects in cerebrovascular disease, and previous studies suggest reduced stroke risk and overall mortality. This study compared post-intracerebral hemorrhage (ICH) outcomes in patients with type 2 diabetes mellitus (T2DM) receiving GLP-1RAs vs other hypoglycemic drugs including insulin. METHODS: We conducted a retrospective cohort study using the global TriNetX network database. Patients with ICH and T2DM were stratified by GLP-1RA exposure, initiation between 5 years before and the day of the ICH and compared with patients treated with other hypoglycemic agents. After 1:1 propensity matching, 3600 patients per cohort were included in the analysis. Outcomes were assessed at 7, 30, and 90 days (all-cause mortality, seizures, craniectomy/craniotomy procedures, and external ventricular drain placement) and at 1 and 5 years post-ICH (all-cause mortality, seizures, palliative care, and respiratory failure). RESULTS: GLP-1RA use was associated with lower 7-day mortality (adjusted hazard ratio [AHR] 0.831, 95% CI 0.703, 0.983), 30-day mortality (AHR 0.835, 95% CI 0.741-0.942), and 90-day mortality (AHR 0.805, 95% CI 0.725-0.894). External ventricular drain insertion was not significantly different at any time point. Craniectomy/craniotomy and seizure risk were not significantly different at 7 or 30 days but were lower by 90 days (craniectomy/craniotomy: 2.8% vs 3.6%; AHR 0.763; seizures: 6.4% vs 7.7%; AHR 0.804). The mortality and seizure benefit persisted at 1 and 5 years. At 1 and 5 years, GLP-1RA use was also associated with reduced need for palliative care (1 year: 10.4% vs 13.1%; AHR 0.754; 5 years: 13.1% vs 16.1%; AHR 0.775) and respiratory failure (1 year: 19.8% vs 22.7%; AHR 0.825; 5 years: 25.2% vs 28.1%; AHR 0.854). CONCLUSION: In this cohort of patients with ICH and T2DM, GLP-1RA use was associated with improved outcomes. Prospective trials are warranted to confirm these observations.