DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20181180

Impact of metformin on the severity and outcomes of ischemic stroke

Vahid Abbasi, Firouz Amani, Ameneh Faraji-Almoti

Abstract


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.


Keywords


Complications, Metformin, Recovery, Stroke

Full Text:

PDF

References


Simon R, Greenberg D, Aminoff M. Clinical neurology 9th Edition; 2015.

Trevor AJ, Katzung BG, Masters SB, Kruidering-Hall M. Basic and Clinical Pharmacology 13th Edition: McGraw-Hill Medical New York; 2015.

Arbeláez-Quintero I, Palacios M. To Use or Not to Use Metformin in Cerebral Ischemia: A Review of the Application of Metformin in Stroke Rodents. Stroke Research and Treatment. 2017;1-13.

Abbasi V, Amani F, Aslanian R, Hoseinkhani A, Zakeri A. Epidemiological Study of Stroke in Ardabil, Iran: a Hospital Based-Study. J Neurol Disord Stroke. 2017;5(3):1128.

Mima Y, Kuwashiro T, Yasaka M, Tsurusaki Y, Nakamura A, Wakugawa Y, et al. Impact of Metformin on the Severity and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus. J Stroke Cerebrovasc Dis [Internet]. 2016;25(2):436-46. Available at: http://www.sciencedirect.com/science/article/pii/ S1052305715005686

Dadwal P, Mahmud N, Sinai L, Azimi A, Fatt M, Wondisford FE, et al. Activating endogenous neural precursor cells using metformin leads to neural repair and functional recovery in a model of childhood brain injury. Stem cell reports. 2015;5(2):166-73.

Ashabi G, Khalaj L, Khodagholi F, Goudarzvand M, Sarkaki A. Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab Brain Dis. 2015;30(3):747-54.

Abd-Elsameea A, Moustaf A, Mohamed A. Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion. Eur Rev Med Pharmacol Sci. 2014;18(16):2387-92.

Deng T, Zheng YR, Hou WW, Yuan Y, Shen Z, Wu XL. Pre-stroke Metformin Treatment is Neuroprotective Involving AMPK Reduction. Neurochem Res. 2016;41(10):2719-27.

Abbasi V, Fattahzadeh-Ardalani G, Safarnejad P, Aslanian R. Albumin impact on clinical practice and complications of ischemic stroke in patients with stroke. Int J Basic Clin Pharmacol. 2016;5:2114-7.

Wu TY, Campbell BC, Strbian D, Yassi N, Putaala J, Tatlisumak T, et al. Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage. European Stroke Journal. 2016;1(4):302-9.

Venna VR, Li J, Hammond MD, Mancini NS, Mccullough LD. Chronic metformin treatment improves post-stroke angiogenesis and recovery after experimental stroke. Eur J Neurosci. 2014;39(12):2129-38.

Kuwashiro T, Kamouchi M, Ago T, Hata J, Sugimori H, Kitazono T, et al. The factors associated with a functional outcome after ischemic stroke in diabetic patients: the Fukuoka Stroke Registry. Journal of the neurological sciences. 2012;313(1):110-4.

Zhou C, Sun R, Zhuang S, Sun C, Jiang Y, Cui Y, et al. Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity. Brain Res Bull. 2016;121:241-5.

Jia J, Cheng J, Ni J, Zhen X. Neuropharmacological Actions of Metformin in Stroke. Curr Neuropharmacol. 2015;13(3):389-94.

Liu Y, Tang G, Li Y, Wang Y, Chen X, Gu X, et al. Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion. Journal of neuroinflammation. 2014;11(1):1.

Jin Q, Cheng J, Liu Y, Wu J, Wang X, Wei S, et al. Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain, behavior, and immunity. 2014;40:131-42.

Jiang T, Yu JT, Zhu XC, Wang HF, Tan MS, Cao L, et al. Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre‐activation of AMPK‐dependent autophagy. British Journal of Pharmacology. 2014;171:3146-57.

Cheng YY, Leu HB, Chen TJ, Chen CL, Kuo CH, Lee SD, et al. Metformin-inclusive therapy reduces the risk of stroke in patients with diabetes: a 4-year follow-up study. Journal of Stroke and Cerebrovascular Diseases. 2014;23(2):e99-e105.