Impact of Metformin on the Severity and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus

Mima, Yohei; Kuwashiro, Takahiro; Yasaka, Masahiro; Tsurusaki, Yuichiro; Nakamura, Asako; Wakugawa, Yoshiyuki; Okada, Yasushi

doi:10.1016/j.jstrokecerebrovasdis.2015.10.016

Cited by 54 publications

(38 citation statements)

References 32 publications

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“…DM is a risk factor for cerebrovascular disease. In the general population, studies have reported that metformin use in patients with DM and without CKD reduces neurological severity and the risk of stroke . In contrast, in our study, the patients with DM and CKD stage 5D (ie, hemodialysis patients with DM) who were metformin users had a significantly higher risk of stroke than did metformin nonusers.…”

Section: Discussioncontrasting

confidence: 82%

“…Metformin improves hyperglycemia by enhancing insulin sensitivity, reducing hepatic glucose release, and elevating muscle uptake of glucose. Many studies have reported that metformin administration to patients with DM before stroke onset may be associated with reduced neurological severity . Moreover, metformin use in patients with DM has been shown to reduce the risk of coronary artery disease and mortality .…”

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confidence: 99%

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Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case–Control Study

Chien

Chou

Chen

et al. 2017

JAHA

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BackgroundMetformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM.Methods and ResultsUsing the National Health Insurance Research Database, we identified 17 760 patients with DM and new‐onset hemodialysis between 2001 and 2013. Of these, 1898 patients hospitalized for either ischemic or hemorrhagic stroke were matched to 7592 control patients according to sex, age, and year of initial hemodialysis therapy by using incidence sampling. The association between metformin use and stroke risk was estimated using conditional logistic regression after adjustment for hemodialysis frequency, comorbidity, and prescribed medications. Metformin use was recorded before the date of stroke admission and the date of pseudostroke of the case and control patients, respectively. Results showed that hemodialysis patients with ischemic stroke were more likely to use metformin than the controls 1 year before the date of stroke admission (adjusted odds ratio: 1.64; 95% confidence interval, 1.32–2.04). The association was evident within 90 days before the index date (adjusted odds ratio: 1.81; 95% confidence interval, 1.27–2.60). The results were consistent with those of hemodialysis patients with hemorrhagic stroke. Metformin use remained a risk factor for stroke in patients treated with antihypertensive, sulfonylurea, and antiplatelet drugs.ConclusionsThis nested case–control study is the first to show that metformin use is associated with stroke risk in hemodialysis patients with DM. We suggest that metformin should not be used by hemodialysis patients with DM.

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Section: Discussioncontrasting

confidence: 82%

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confidence: 99%

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case–Control Study

Chien

Chou

Chen

et al. 2017

JAHA

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“…They followed up 14,856 patients and estimated a nearly 50% reduction in stroke episodes (adjusted hazard ratio 0.46, 95% CI: 0.424–0.518, p < 0.001) in patients with diabetes treated with metformin versus patients who did not use metformin [11]. The clinical benefit of metformin in diabetic patients for stroke prevention was described in a retrospective analysis by Mima et al who reported a reduction in the severity of neurological symptoms [12]. …”

Section: Introductionmentioning

confidence: 99%

To Use or Not to Use Metformin in Cerebral Ischemia: A Review of the Application of Metformin in Stroke Rodents

Arbeláez-Quintero

Palacios

2017

Stroke Research and Treatment

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Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects. Most experiments done in the cerebral ischemia model, via middle cerebral artery occlusion in rodents (MCAO), had positive results favoring metformin's neuroprotective role and involve several cellular pathways like oxidative stress, endothelial nitric oxide synthase activation, activation of angiogenesis and neurogenesis, autophagia, and apoptosis. We will review the pharmacological properties of metformin and its possible mechanisms that lead to neuroprotection in cerebral ischemia.

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“…The location of the CNS is guessed according to the type of symptoms and diagnosed by neurologic examination and confirmed by uses CT-scan and MRI. 2,3,5,6 The UKPDS study reported that treatment with Metformin decreases the risk of large vascular disease similar to small vascular disease. This is the opposite of other therapies that only reduce the deaths caused by sall vessels.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the initial score of NIHSS, occurrence of stroke relapse was related with increasing stroke severity and mild prognosis of stroke. 5,16,17 Jiang and et al in a study showed that the drugs such as metformin, pioglitazone and semaglutin were effective in the decreasing the risk of stroke. 18 In a sample of 14856 diabetic patients from Taiwan after 4 years follow-up, the relation between metformin uses and stroke reducing wasn't significant.…”

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confidence: 99%

Impact of metformin on the severity and outcomes of ischemic stroke

Abbasi

Amani

Faraji-Almoti

2018

Int J Basic Clin Pharmacol

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Background: Stroke is the third most common cause of death in the United States and the most commonly diagnosed neurological disorder. About 750,000 strokes occur annually in the United States and about 150,000 people die as a result of stroke. The aim of this study was evaluation of the effect of Metformin on complication of ischemic strokes.Methods: In this randomized, double-blind clinical trial study, 100 patients with ischemic stroke will be assigned randomly into two groups A and B. The National Institutes of Health Stroke Scale (NIHSS) will be used to evaluate the clinical manifestations of ischemic stroke. The two groups will be followed up for 3 months. Metformin 500mg twice in a day will be administered for seven days for group (A) and placebo will be administered for seven days for group (B). Blood glucose will be checked every 6 hours and will be recorded on the blood glucose (BS) chart. Before the intervention, the NIHSS questionnaire will be recorded in one day, three days, seven days and one month, two months, and three months after the intervention will be followed up respectively.Results: In the present study, according to the neuro-protective effects of metformin, there is a significant difference in metformin taking in the reduction of NIHSS Score in non-diabetic stroke patients. There was a significant association in metformin taking and decrease in NIHSS scores in patients with cortical ischemic stroke.Conclusions: According to the results, in patients with cortical stroke, there weren’t a significant difference in NIHSS between the two groups in the first, third and seventh days but in the first, second and third months after intervention the difference was significant. Also, the results showed that metformin reduced the severity and stroke symptoms and accelerated recovery and functional output in patients with cortical stroke after the first, second and third months.

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Impact of Metformin on the Severity and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus

Cited by 54 publications

References 32 publications

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case–Control Study

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case–Control Study

To Use or Not to Use Metformin in Cerebral Ischemia: A Review of the Application of Metformin in Stroke Rodents

Impact of metformin on the severity and outcomes of ischemic stroke

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