To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: ENDO 99: Avandia Reduces Insulin Resistance, Lowers Blood Sugar URL: http://www.pslgroup.com/dg/107A56.htm Doctor's Guide June 15, 1999
SAN DIEGO, CA. -- June 15, 1999 -- Avandiaź (rosiglitazone maleate, SmithKline Beecham) reduces insulin resistance, an underlying cause of type 2 diabetes, and significantly lowers blood sugar levels in people with type 2 diabetes, according to a study presented today at the annual scientific session of the Endocrine Society, ENDO 99. Insulin resistance, when left untreated, may ultimately lead to the exhaustion of pancreatic beta-cells (insulin producing cells in the pancreas) trying to compensate for the body's insensitivity to insulin. Avandia works by directly targeting insulin resistance.
Avandia was recently approved by the Food and Drug Administration both as montherapy and in combination with metformin. Avandia is a new thiazolidinedione (TZD) agent, a class of novel, oral antidiabetic agents that improve glycemic control and directly target insulin resistance.
Type 2 diabetes affects an estimated 15 million Americans and is the country's sixth leading cause of death.
Homeostasis Model Assessment (H0MA) Data indicate that Avandia, alone or in combination with metformin or sulfonylurea, improved both insulin sensitivity and estimates of beta-cell function in type 2 diabetes patients. Results were measured using the Homeostasis Model Assessment (HOMA), a mathematical model that permits estimation of beta-cell function and insulin sensitivity from fasting plasma insulin and glucose values.
"Clinical researchers are turning to the HOMA model to gain useful information on large patient populations," said Dr. Harold Lebovitz, Professor of Medicine at State University of New York Health Science Center in Brooklyn.
"HOMA is cost-effective and non-invasive and one of the more useful ways to assess insulin resistance and to estimate beta-cell function."
Avandia: Impact on Insulin Sensitivity and Beta-Cell Function Estimates
Patients given a combination of either 4 or 8 mg Avandia once daily plus metformin showed improvement in both insulin resistance and estimates of beta-cell function. Insulin resistance declined by an average of 20.4 percent and estimates of beta-cell function increased by an average of 94.2 percent, in patients taking Avandia 8 mg once daily plus metformin.
In patients given Avandia monotherapy, insulin resistance decreased by an average of 16 and 25 percent and the estimate of beta-cell function increased by an average of 50 and 60 percent for 4 and 8 mg/day, respectively. For patients on placebo, insulin resistance increased by an average of 7.9 percent, and the estimate of beta-cell function decreased by an average of 4.5 percent.
Adding Avandia (1 or 2 mg twice daily) to sulfonylurea therapy was associated with improvement in both insulin resistance and the estimate of beta-cell function. Insulin resistance declined 17.4 percent and the estimate of beta-cell function showed improvement by an average of 72 percent at a dose of 4 mg/day. Patients receiving sulfonylurea monotherapy had an average increase of 8.6 percent in the estimate of beta-cell function, consistent with the drug's mechanism, which is to stimulate insulin production. These sulfonylurea monotherapy patients did not achieve adequate glycemic control during this study. Moreover, in these patients, insulin resistance increased by 15 percent. Avandia in combination with sulfonylurea is not yet approved in the United States.
"If beta-cell function can improve with therapy, a possibility supported by animal studies reported at last year's Endocrine Society meeting, patients who use this new agent may reap the benefit of reduced stress on the pancreas," continues Dr. Lebovitz. "Additional studies to assess the effect of Avandia on long-term glycemic control and beta-cell function are under way."
Avandia Significantly Improves Blood Sugar Control
Additional data on the safety and efficacy of Avandia were presented at the meeting. These data were drawn from clinical studies of patients who failed to achieve adequate control of blood sugar with diet and exercise or with oral antidiabetic medications.
In each of the three studies, patients treated with Avandia monotherapy had significant decreases in fasting plasma glucose levels and hemoglobin A1c (i.e., a measure of blood sugar levels over time).
In two trials, Avandia was compared to placebo and produced mean decreases in fasting plasma glucose of up to 76 mg/dL and mean decreases in hemoglobin A1c of up to 1.5 percentage units compared to placebo. In the third study, Avandia was compared to a sulfonylurea and was shown to produce comparable improvements in blood glucose control at the end of one year.
Prior to study entry, over 500 of the patients in these three trials had received no antidiabetic medications. Among these patients substantial proportions achieved hemoglobin A1c levels less than or equal to 8% (ADA Treatment Action Point) by the study end-point: from 59% of those who received a total daily dose of 4mg to 86% of those receiving a total daily dose of 8mg.
Adverse Events
Avandia was well tolerated in clinical trials. Commonly reported adverse events with Avandia were upper respiratory tract infections and headaches.
Improvement in glycemic control was associated with a mean increase in weight of (4-7 pounds over 12 months). Additionally, anemia and edema have been reported in patients taking Avandia. There have been no reported cases of drug-related hepatoxicity or elevations in ALT in Avandia clinical studies of nearly 4,600 patients. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.