NEW ORLEANS, LA, April 4, 2000 – Adding a newer anti-diabetes drug, rosiglitazone [also know as AvandiaÒ , SmithKline Beecham] to an older medication, metformin [also known as GlucophageÒ , Bristol Myers Squibb], significantly reduced blood-sugar levels in type 2 diabetes patients compared with Glucophage alone, according to study results published in today’s issue of the Journal of the American Medical Association (JAMA). The study also showed the Avandia and Glucophage combination significantly improved the control of insulin resistance and increased insulin production by the pancreas, suggesting that the drug combination may delay or prevent disease progression. According to the landmark UKPDS study, approximately half of patients taking only Glucophage and other older anti-diabetes drugs eventually need some type of combination therapy to effectively manage their disease.

"Using Glucophage alone often fails over time and many patients require the addition of another drug to adequately control their diabetes," says lead study author Vivian Fonseca, MD, Professor of Medicine, Tullis-Tulane Alumni Chair in Diabetes at the Tulane University School of Medicine. "This study shows that combining Avandia with Glucophage may prevent the long-term complications of diabetes such as heart disease, blindness, limb loss and kidney failure, by providing more effective blood sugar control than Glucophage alone."

In a multicenter, double-blind, placebo-controlled trial, 348 patients inadequately controlled on a maximum dose (2.5 grams once daily) of Glucophage were randomized to receive 2.5 mg of Glucophage and either a placebo, 4 mg of Avandia, or 8 mg of Avandia once daily. Fasting plasma glucose or FPG and glycosylated hemoglobin or HbA_1c, two important blood-sugar measures, as well as insulin sensitivity and insulin production by pancreatic beta cells, were measured for all groups in order to determine the effectiveness of Avandia and Glucophage in combination compared to Glucophage plus placebo.

Study results showed that Avandia and Glucophage in combination significantly decreased both FPG and HbA_1c in patients compared to Glucophage and placebo alone. Decreases were observed within four weeks and were sustained throughout the study. Among patients treated with Avandia (8 mg) and Glucophage (2.5 mg), 30 percent achieved HbA_1c of 7 percent and nearly 60 percent achieved levels of 8 percent. Among patients given Glucophage and placebo only, 7.6 percent achieved HbA_1c levels of 7 percent and 35 percent achieved HbA_1c of 8 percent. The American Diabetes Association recommends a target HbA_1c of 7 percent, or at least 8 percent.

Study results also showed the addition of Avandia to Glucophage significantly decreased insulin resistance and increased insulin production. Using a mathematical model that estimates pancreatic beta cell function and insulin sensitivity from fasting plasma insulin and glucose values, the study indicated that insulin resistance decreased significantly with Avandia in combination with Glucophage. Additionally, the combination improved the function of the pancreas, compared to placebo.

"What this means for patients and physicians is that this combination may result in better control of type 2 diabetes," says Dr. Fonseca. "For patients who are controlled inadequately on Glucophage alone, physicians should consider adding Avandia to their treatment regimen to help patients better manage their disease."

In the study, increases in body weight, total cholesterol, and LDL cholesterol were observed. The proportion of patients reporting adverse experiences was comparable across all groups. The most frequently reported adverse events in both groups were upper respiratory infection, diarrhea and headache. No serious adverse events were considered related to study medication. Elevated liver enzymes of greater than three times the upper limit of normal were not observed in any study patients.

Avandia is a thiazolidinedione (TZD), a novel class of oral antidiabetic agents that treat the symptoms of type 2 diabetes and directly target insulin resistance, the underlying cause of type 2 diabetes. Avandia was approved in 1999 by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes as monotherapy and in combination with Glucophage. The FDA approved Glucophage in March 1995 as a monotherapy adjunct to diet to lower blood sugar in patients with type 2 diabetes whose high blood-sugar cannot be satisfactorily managed on diet alone. Avandia primarily targets insulin resistance, the underlying cause of type 2 diabetes, while Glucophage works by decreasing sugar output through the liver.

"Understanding the mechanisms that cause high blood sugar helps physicians choose the appropriate medication or combination of medications from the increasing number of drugs now available for type 2 diabetes," says Dr. Fonseca.

Diabetes, which is the sixth highest cause of death by disease in the United States, strikes an estimated 16 million Americans—90 to 95 percent of whom have type 2 diabetes. Type 2 diabetes is one of the most costly health problems in America due to its devastating complications. It is the leading cause of adult blindness, kidney failure and non-traumatic limb loss in the United States. Diabetes is a chronic disease characterized by high blood-sugar levels that result from defects in the body’s ability to use and/or produce insulin. There are two main types of diabetes: type 1 and type 2. People with type 1 diabetes are usually diagnosed when they are children or young adults. In type 1 diabetes, the pancreas makes little or no insulin, so patients must test their blood sugar and inject insulin every day. In type 2 diabetes, the pancreas continues to produce insulin, but the body inefficiently uses the insulin. Many patients with type 2 diabetes will eventually require insulin injections.

Updated April 04, 2000 - © 2000-2010 GlaxoSmithKline - All Rights Reserved Legal Notices - Privacy Statement