Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage

Introduction: Few proven therapies for intracerebral haemorrhage exist. Preliminary observational evidence suggests that sulphonylurea and metformin may be protective in ischaemic stroke. We assessed the association of pre-intracerebral haemorrhage sulphonylurea and metformin use on outcome in diabetic patients. Methods: We merged datasets from the consecutive single-centre Helsinki ICH Study, the intracerebral haemorrhage arm of the Virtual International Stroke Trials Archive (VISTA-ICH) and the Royal Melbourne Hospital ICH Study. Logistic regression adjusting for known predictors of intracerebral haemorrhage outcome (age, sex, baseline Glasgow Coma Scale, National Institutes of Health Stroke Scale, intracerebral haemorrhage volume, infratentorial location, intraventricular extension, and pre-intracerebral haemorrhage warfarin use) estimated the association of metformin and sulphonylurea with all-cause 90-day mortality. Results: From a dataset of 2404 consecutive intracerebral haemorrhage patients, we included 374 (16%) patients with diabetes. Of these, 113 (30%) died by 90 days. Metformin was used in 148 (40%) patients and sulphonylurea in 115 (31%) patients at intracerebral haemorrhage onset. After adjusting for baseline characteristics, metformin use was associated with lower 90-day mortality (OR 0.51; 95% CI 0.26–0.97; p = 0.041) irrespective of whether the drug was continued or not during the admission, while sulphonylurea use was not associated with mortality (OR 0.96; 95% CI 0.49–1.88; p = 0.906). Haematoma location or evacuation did not modify the association between metformin and mortality; neither did adding insulin use, baseline glucose and serum creatinine into the model (OR 0.50; 95% CI 0.25–0.99; p = 0.047). Conclusion: Pre-intracerebral haemorrhage metformin use was associated with improved outcome in diabetic intracerebral haemorrhage patients. Our results generate hypotheses which after further validation could be tested in clinical trials.