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Purpose: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism.Data Sources: Data were obtained from a MEDLINE search back to 1966 and included animal and human studies published in the English language.Study Selection: Approximately 80% of original publications were included after review by the authors. Case reports were included if they provided additional information. DATE EXTRACTION: The original data from the literature were included on the basis of independent extraction by the authors.Data Synthesis: Many common therapeutic agents influence glucose metabolism. Multiple mechanisms of action on glucose metabolism exist through pancreatic, hepatic, and peripheral effects. Based on circumstances at the time of use, a drug may cause both hyper- and hypoglycemia in a patient. The patient's previous pancreatic reserve, nutritional state, use of other medication, or exposure to alcohol may influence the direction of the plasma glucose alterations.Conclusion: Hyperinsulinemia and insulin resistance form an intrinsic component of diabetes, hyperlipidemia, and atherosclerotic vascular disease (syndrome X). The induction of hyperinsulinemia and insulin resistance by medication may therefore counteract intended benefits. An extensive review of recent medication in patients with disorders of glucose tolerance and the avoidance of polypharmacy are recommended. It is prudent to monitor plasma glucose values when it is not possible to avoid prescription of medication with known effects on carbohydrate metabolism. [ABSTRACT FROM AUTHOR]