The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals.\r\nIn this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic\r\nproperties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction,\r\nhemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have\r\ncontributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin�s mere\r\nantihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing\r\nthe need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is\r\nincreasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a\r\nneuroprotective effect. Metformin�s negligible risk of hypoglycemia in monotherapy and few drug interactions of\r\nclinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an\r\nappropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an\r\nextended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and\r\ndescribe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin\r\nresistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes,\r\ncancer, and neuroprotection.
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