Metformin/rosiglitazone combination pill (Avandamet) for the treatment of patients with Type 2 diabetes.
More than 150 million people worldwide have diabetes, the prevalence of which is increasing so rapidly that the number of adults with diabetes in the world will rise to 300 million by the year 2025. In the US, approximately 21 million people have diabetes and in some areas of the country, the prevalence is as high as 50%. The pathophysiologic hallmarks consist of insulin resistance and progressive pancreatic beta-cell dysfunction. An increased metabolic demand for insulin due to increased insulin resistance usually precedes the development of hyperglycemia. At early stages, pancreatic beta cells compensate for insulin resistance by hypersecretion of insulin. However, the period of beta-cell compensation is followed by beta-cell failure, in which the pancreas fails to secrete sufficient insulin and diabetes ensues. Biguanides and thiazolidinediones (TZDs) are two unique classes of oral antidiabetic agents that are the most commonly used medications to improve insulin sensitivity. They have no direct effect on beta-cell function, although some indirect mechanisms of actions may help to preserve beta-cell function or slow beta-cell apoptosis. Their glucose-lowering effect results from improving insulin sensitivity in a complementary fashion: metformin reduces hepatic glucose production and TZDs increase skeletal muscle glucose use. The combination of metformin and rosiglitazone in a single pill (Avandamet), was approved by the FDA in October 2002 for the treatment of diabetes. As insulin resistance is a pathophysiologic cornerstone of diabetes and cardiovascular disease, the use of Avandamet represents an optimal approach to the treatment of diabetes. This manuscript reviews the pharmacology, safety and benefits of the combination pill Avandamet.
Smiley
Dawn
D
Emory University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, 49 Jesse Hill Jr. Drive, Atlanta, Georgia 30303, USA. dsmiley@emory.edu
Umpierrez
Guillermo
G
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004338:Drug Combinations; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
D004338:Drug Combinations; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D005947:Glucose