Triple-Drug Therapy May Improve Sugar Control in Adults with Diabetes

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The summary below is from the full report titled "The Effect of a Thiazolidinedione Drug, Troglitazone, on Glycemia in Patients with Type 2 Diabetes Mellitus Poorly Controlled with Sulfonylurea and Metformin. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial." It is in the 1 May 2001 issue of Annals of Internal Medicine (volume 134, pages 737-745). The authors are JF Yale, TR Valiquett, MN Ghazzi, JK Owens-Grillo, RW Whitcomb, and HL Foyt, for the Troglitazone Triple-Therapy Study Group.

What is the problem and what is known about it so far?

Diabetes is a chronic condition that can lead to damage of the eyes, heart, kidneys, and nerves. People with diabetes have persistent elevations in blood sugar levels. Treatments that can lower blood sugar levels include diet, exercise, insulin injections, and medications. Metformin and sulfonylurea are types of medications commonly used to treat adults with diabetes. Many diabetic adults take several medications but still have trouble controlling their sugar levels. A newer type of medication, thiazolidinediones, can help control blood sugar; it is not clear, however, whether these newer drugs are effective in adults who are already taking metformin and sulfonylurea.

Why did the researchers do this particular study?

To see whether adding troglitazone, a thiazolidinedione drug, would lower blood sugar levels in diabetic adults with inadequate sugar control despite treatment with metformin and sulfonylurea.

Who was studied?

The study included 200 middle-aged Canadian men and women with diabetes. All had high levels of blood sugar despite treatment with both metformin and sulfonylurea.

How was the study done?

Patients continued taking metformin and sulfonylurea. In addition, they were given either troglitazone pills or identical-appearing placebo pills that contained no active ingredient. Neither patients nor doctors knew who was getting troglitazone or placebo. Patients were encouraged to monitor their own blood sugar levels. At monthly clinic visits, they were asked about side effects and had blood tests done. After 6 months, the researchers compared blood sugar levels in patients given troglitazone with sugar levels in those given placebo.

What did the researchers find?

Patients taking troglitazone had lower average blood sugar levels than those taking placebo. About 15% of troglitazone-treated patients reached optimum levels of blood sugar control, while 1% to 4% of those given placebo achieved optimum control. However, 31% of troglitazone-treated patients had episodes of low blood sugar with such symptoms as nausea and shakiness; 13% of patients given placebo had episodes of low blood sugar.

What were the limitations of the study?

Troglitazone, the drug used in this study, was withdrawn from the U.S. market in 2000 because it caused severe liver failure in several patients. Other thiazolidinedione drugs are still marketed in the United States, but this study does not tell us whether the effects of those other drugs are exactly the same as those of troglitazone.

What are the implications of the study?

Troglitazone added to metformin and sulfonylurea drugs improved overall sugar control in adult diabetic patients, but it also caused symptomatic episodes of low blood sugar. This particular drug is no longer marketed in the United States, although other drugs of this type are available.