Association of prestroke metformin use, stroke severity, and thrombolysis outcome

Abstract

Objective:To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after intravenous thrombolysis (IVT), we analyzed a cohort of 1919 stroke patients with type-2 diabetes in a multicenter exploratory analysis.Methods:Data from patients with diabetes affected by ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.Results:Of 1919 stroke patients with type-2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets or antihypertensives were more common in the MET+ group. After PSM, the two groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIHSS 10.0 ± 6.7 vs. 11.3 ± 6.5), 3-months degree of independence on modified Rankin Scale (mRS): 2 [IQR 1.0, 4.0] vs. 3 [IQR 1.0, 4.0] as well as mortality (12.5% vs. 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well balanced between both groups.Conclusions:Stroke patients with diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.

Evaluation of the Effectiveness of Post-Stroke Metformin Treatment Using Permanent Middle Cerebral Artery Occlusion in Rats

“…It is important to mention that recent clinical studies revealed that pre-treatment with metformin resulted in less severe strokes, beneficial thrombolysis outcome and reduced neurological deficits in diabetic patients [48,49]. Thus, these results suggest that metformin has a neuroprotective effect, although there is a lack of post-ischemic treatment studies in non-diabetic patients.…”

Association of triglyceride-glucose index with clinical outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis

“…The Insulin Resistance Intervention after Stroke (IRIS) trial which involved 3876 patients, demonstrated that pioglitazone, an insulin-sensitizer, reduced the risk of recurrent stroke and myocardial infarction in patients without diabetes who had recent ischemic stroke or TIA 11 . Others observed associations between prior metformin use and better neurological outcomes in patients with AIS and those who received thrombolytic therapy 60 . A meta-analysis on glucagon-like peptide-1 (GLP-1) receptor agonists like liraglutide, which work by glucose-dependent insulin release, have shown benefits for primary stroke prevention 61 .…”

Metformin Inhibits NLR Family Pyrin Domain Containing 3 (NLRP)-Relevant Neuroinflammation via an Adenosine-5′-Monophosphate-Activated Protein Kinase (AMPK)-Dependent Pathway to Alleviate Early Brain Injury After Subarachnoid Hemorrhage in Mice

“…The recent literature has hinted that metformin plays a beneficial role in improving the poor prognoses of patients with brain injury. A multicenter retrospective analysis indicated that stroke patients with diabetes who were treated with metformin showed less-severe stroke on admission and better functional outcomes at 3 months than stroke patients with diabetes who were not treated with metformin ( Westphal et al, 2020 ). Therefore, whether metformin can improve the long-term outcomes of SAH and whether it exerts beneficial clinical effects on SAH patients must also be considered in future studies.…”