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  • Title: Metformin: an antihyperglycemic agent for treatment of type II diabetes.
    Author: Melchior WR, Jaber LA.
    Journal: Ann Pharmacother; 1996 Feb; 30(2):158-64. PubMed ID: 8835050.
    Abstract:
    OBJECTIVE: To review the comparative efficacy of metformin, sulfonylureas, and insulin in the treatment of patients with type II diabetes. DATA SOURCES: Articles were identified by a MEDLINE search of articles from 1966 to 1994, using the terms metformin, sulfonylurea, chlorpropamide, glipizide, glyburide, tolazamide, tolbutamide, and insulin, published in English, French, or German. Articles also were identified from bibliographies of pertinent articles. STUDY SELECTION: With the exception of articles dealing with the pharmacology of metformin, only randomized, active, controlled studies were selected for review. DATA EXTRACTION: Effects of metformin therapy on metabolic and cardiovascular risk factors were abstracted: weight, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, fasting and postprandial glucose, and glycosylated hemoglobin. DATA SYNTHESIS: Metformin is an antihyperglycemic agent with a mean bioavailability of 50-60%. It is eliminated primarily by renal filtration and secretion and has a half-life of approximately 6 hours in patients with type II diabetes. Although the half-life of metformin is prolonged in patients with renal impairment, no specific dosage adjustments have been recommended. This agent has no effect in the absence of insulin. Metformin is as effective as the sulfonylureas in treating patients with type II diabetes and has a more prominent postprandial effect than the sulfonylureas or insulin. When combined with a sulfonylurea, metformin has been shown to exert antihyperglycemic effects in addition to the sulfonylurea with which it is combined. Metformin decreases absorption of vitamin B12 and folic acid, although reported cases of megaloblastic anemia are rare. Cimetidine decreases the elimination of metformin; therefore, the manufacturer reccommends a reduced metformin dosage when these agents are combined. The most frequently reported adverse effects of metformin are gastrointestinal in nature (diarrhea, nausea, abdominal pain, and metallic taste, in decreasing order). Metformin has been used in Canada, Great Britain, and the rest of Europe for more than 30 years and was approved for use in the US in December 1994. CONCLUSIONS: Three trials comprise the Food and Drug Administration approval database (one foreign). Metformin will be most useful in managing patients with poorly controlled postprandial hyperglycemia, as its postprandial effect is much greater than that of the sulfonylureas. In contrast, sulfonylureas or insulin are more effective for managing patients with poorly controlled fasting hyperglycemia. Metformin should be considered a first-line agent, particularly in obese or hyperlipidemic patients.
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