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Biguanides are a group of oral hypoglycemic agents that are chemically and pharmacologically distinct from the sulfonylureas. One biguanide, phenformin, was briefly used in the United States more than 30 years ago but was withdrawn from the market because it pro-duced severe lactic acidosis in some patients. Metformin (Glucophage) was used in Europe for many years be-fore it was approved for use in the United States in 1995. Metformin is the only approved biguanide for the treatment of patients with NIDDM that are refractory to dietary management alone. Metformin does not af-fect insulin secretion but requires the presence of in-sulin to be effective. The exact mechanism of met-formin’s action is not clear, but it does decrease hepatic glucose production and increase peripheral glucose up-take. When used as monotherapy, metformin rarely causes hypoglycemia.
Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance. The United Kingdom Prospective Diabetes Study demon-strated a marked reduction in cardiovascular comor-bidities and diabetic complications in metformin-treated individuals. Metformin has also been used to treat hirsutism in individuals with polycystic ovarian syndrome and may enhance fertility in these women, perhaps by decreasing androgen levels and enhancing insulin sensitivity.
Adverse gastrointestinal symptoms (nausea, vomit-ing, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking met-formin; this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypox-emia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics.
Two relatively new formulations of metformin are available. Glucovance is a combination of metformin and glyburide that may be helpful for diabetics who re-quire both a sulfonylurea and metformin, and Glu-cophage XR is an extended-release product of met-formin that may be better tolerated in some patients who are prone to gastrointestinal side effects. Met-formin is usually given two to three times a day at meal-times.
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