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Update on Rezulin (troglitazone)

Manufacturer: Parke-Davis Pharmaceuticals, Ltd.

FDA Approval: January, 1998

Treatment for: Type 2 diabetes

Mechanism of action: Improves the action of insulin by stimulating a gene to produce more proteins at the site where insulin acts. These proteins aid in the removal of glucose from the bloodstream.

Indications for use: May be used with sulfonylurea or insulin or as a single drug therapy in conjunction with diet and exercise. Not recommended for use in type 1 diabetes. Not recommended as a substitute for sulfonylurea in patients previously well controlled on sulfonylurea therapy.

Some of you have asked for information on the diabetes drug Rezulin since news surfaced this summer concerning its safety. In trials preceding approval, the main adverse effects seen were fluid retention and elevation of liver enzymes in approximately 2% of participants taking troglitazone. Since public distribution of the drug, five cases of severe liver injury have been reported. Recently, a large, federally funded trial discontinued investigation of troglitazone in the prevention of type 2 diabetes. (The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the direction of the federal government's National Institutes of Health (NIH), is funding a multi-center trial to investigate preventative treatments for type 2 diabetes. This Diabetes Prevention Program (DPP) had four arms: Rezulin (troglitazone), Glucophage (metformin), and 2 lifestyle changes. In June 1998 the NIDDK ended the study of troglitazone in the DPP following the death on May 17, 1998 of a participant. It was determined that troglitazone induced liver toxicity and was probably the cause of liver failure in this patient. The other arms of the study are expected to continue.)

Such severe adverse reactions to the drug are rare. Liver injury is usually reversible following discontinuation of the drug. However, in light of recent concerns, the FDA now recommends more rigorous testing. Parke-Davis advises liver function tests monthly for the first 8 months of Rezulin therapy, every two months for the remainder of the first year, and periodically thereafter.

Another characteristic of troglitazone therapy is its tendency for causing weight gain when used in conjunction with sulfonylurea. Clinical trials documented weight gains of 5.8 to 13.1 pounds when troglitazone was taken with the sulfonylurea glyburide. The combination therapy was more effective at lowering blood glucose than either therapy alone. The weight gain was on the order of that seen when starting insulin therapy. Following a weight-maintenance diet can avert undesired weight gain.

Rezulin (troglitazone) still proves to be a viable medical therapy in the treatment of type 2 diabetes. The American Diabetes Association, along with the FDA believe there are clear benefits to using this drug in appropriately selected and monitored patients. We will undoubtedly learn more about its risks and benefits as it continues to be utilized in the battle against diabetes. Until then, physicians and patients should be made aware of possible risks, and blood values should be monitored while on this therapy.

Links:

Food and Drug Administration
American Diabetes Association
Parke-Davis Pharmaceuticals, Ltd.
ADA's statement regarding Rezulin
ADA's excellent fact sheet on Rezulin

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