Brand Name: Avandia
Active Ingredient: rosiglitazone maleate
Indication: For the treatment of Type 2 diabetes mellitus
Company Name: SmithKline Beecham Pharmaceuticals
Availability: Prescription only
Approved by FDA: 25 May 1999
Introduction
Despite a growing understanding of the pathophysiology of diabetes mellitus, the long-term management of the disease remains one of the greatest challenges for clinicians. As the number of persons in the US with Type 2 diabetes continues to grow, so does the search for novel, effective and well tolerated therapies. Among the newest forms of therapies are drugs that sensitize the insulin receptor to the action of insulin. The first drug in this class approved in the US was Rezulin (troglitazone). Despite its widespread use and generally good tolerability profile, concerns have been raised about the effect of Rezulin on the liver. Now, Avandia (rosiglitazone) promises to provide good effectiveness while improving on the safety profile of this class of drugs.
How It Works
Insulin exerts its effects by linking to a cellular receptor. Following this interaction, the metabolism of glucose is altered in the cell. Evidence indicates that persons with Type 2 diabetes (formerly known as noninsulin-dependent diabetes) have a defect in their cells that results in reduced responsiveness to insulin. As a class, the thiazolidinediones (also called the “glitazones”) act by “sensitizing” receptors, known as PPAR-gamma receptors, to the effects of insulin. Consequently, the depressed levels of insulin found in persons with Type 2 diabetes achieve a near-normal physiologic effect. Patients who have responded poorly to other traditional oral diabetes therapies, and who have not reached the point where they require insulin injections, appear to respond favorably to Avandia.
Clinical Study Results
Rosiglitazone is one of the most potent members of the thiazolidinediones. Several studies have demonstrated the effectiveness of the drug in persons with diabetes. In one study, 380 diabetics received 12 weeks of treatment with doses ranging from 0.1 mg to 4 mg (given as a twice daily dose). The drug significantly lowered blood glucose compared to placebo, without an accompanying rise in fasting insulin. One fourth of patients receiving the highest dose had complete normalization of their fasting glucose level. The magnitude of effect was considered to be similar to that observed with an 800 mg daily dose of troglitazone. Similar results were observed in a second study of 493 patients.
Some evidence suggests that Avandia’s activity is enhanced when it is given concomitantly with another oral diabetes drug, metformin. Also, Avandia may be slightly more effective in women than in men, although the reasons for this are unclear.
What The Patient Should Know
All antidiabetic drugs, including Avandia, have the potential to cause low blood sugar levels. The dose must be carefully adjusted to ensure adequate control of blood sugar levels but without the development of hypoglycemia.
Because of the development of severe liver damage in some patients who had been treated with troglitazone, the liver safety profile of Avandia remains a concern. However, there has been no indication of hepatotoxicity in controlled clinical trials with Avandia. Nevertheless, it is recognized that hepatic adverse events occur in a very small minority of patients, and that if these adverse events occur with Avandia, they will not be seen until the drug is used by hundreds of thousands of patients.