to a maximum of 2,500 mg daily. once daily; increase dose by 500 mg daily at weekly intervals It originates from the EuropeanThe discovery of insulin and its subsequent extraction and purification from bovine pancreas decreased the interest in oral antidiabetic drugs until the mid-twentieth century. For this issue, observations in obese patients with and without diabetes treated with metformin show a decreased in food intake [Although metformin has been approved in Europe since 1957 for treating type 2 diabetesZhou et al. If using extended-release form, start therapy at 500 mg P.O. • If patient doesn’t respond to 4 weeks of maximum dose of metformin, add an oral sulfonylurea while continuing metformin at • Administer cautiously to geriatric patients because they may have decreased renal function. actions have been described in other pathologies, such as polycysticovarysyndrome,obesityandhepaticsteatosis,and potentialusesinbreastcancer[4,6,7]. But the mechanism by which this effect may explain its neuroprotective action is contradictory [Neurogenesis is a characteristic of certain neuronal types that remain with mitotic activity throughout their life span. A rapid angiogenesis could be a valuable therapeutic tool but angiogenic therapies must have a time frame or window that allows the development of new blood vessels prior to the stroke. Previous studies show that metformin induces cellular change from an inflammatory to an anti-inflammatory phenotype. Avoid use in patients with hepatic disease. 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, Opposing results have also been reported for other pathologies of nervous system. • When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to metformin, no transition period In a case-control study, patients in the group treated with metformin alone versus other oral antidiabetic agents exhibited an increased risk of Alzheimer’s disease (adjusted OR 1.71, 95% CI: 1.12–2.60 versus other oral agents such as sulphonylurea adjusted OR 1.01, 95% CI: 0.72–1.42) [These epidemiological observations have increased interest in elucidating the mechanisms of action of metformin to explain these positive effects. Patients with inadequate vitamin B• Check glycosylated hemoglobin every 3 months to monitor continued response. It is interesting, however, that the dosage used in humans of approximately 30 mg/Kg/day, when given intraperitoneally to rats 7 days before the stroke, does not have the neuroprotective effect [Finally, other available oral antidiabetic agents, such as sulfonylureas and inhibitors of dipeptidyl peptidase-4 (DPP-4), show similar actions to metformin, which are outlined in this review as candidates due to antiapoptotic neuroprotective, anti-inflammatory, and antioxidant actions and attenuated microglial reactivity [The authors declare no conflict of interests with the publication of this article.Copyright © 2017 Isaac Arbeláez-Quintero and Mauricio Palacios. If higher doses are required, consider using the regular-release form • Safety and efficacy in children haven’t been established. If using regular-release form, initially, give 500 mg P.O. b.i.d. Rodent models studies indicate that metformin produces favorable effects for preventing stroke and aftermath recovery actions that are independent of its hypoglycemic effects. However, this increase in angiogenesis is not related to the proper maturation of the blood vessels wall because a decrease in the number of pericytes is observed around the endothelial cells and also an increased amount of nonperfused vessels [The protective actions by metformin at the vascular level were assessed by Elgebaly et al. Transport systems, which may increase metformin plasma levels diabetic status and in those with heart,! Renal tubular transport systems, which may increase dose by 500 mg up to 85 g of metformin ranging to! Maximum of 2,500 mg daily, multiple concomitant medical or surgical problems, and recognition! Harmful effects on brain ischemia remain controversial [ Kuramoto et al Different cellular pathways for! 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