TZDs: Targeting Insulin Resistance Amid Controversy

How It Works

The precise mechanism of these agents is not yet known, but researchers think Avandia and Actos, part of a family of drugs (only two currently approved in U.S.; others are under development) called thiazolidinediones, or TZDs, work by sensitizing muscle and fat to the action of insulin, combating insulin resistance.

If you have insulin resistance, your body doesn't respond to insulin to normalize glucose levels. Insulin resistance is at center stage in causing high blood pressure, lowering HDL (good) cholesterol, and increasing triglycerides, among other problems. With type 2 diabetes, the insulin-producing beta cells of the pancreas begin to die off. TZDs improve beta cell function and may prevent the death of these cells. This leads to more of the body's own natural insulin being made.

Clinical studies have shown TZDs (or glitazones) are effective in lowering blood glucose levels in people with type 2 diabetes when taken alone with a healthful meal plan or in combination with a sulfonylurea or metformin. The average decrease in A1C is 1 to 1.5 percentage points, about 30 to 45 mg/dl on a blood glucose meter.

Improved lipid profiles may be another benefit, as indicated by the COMPLEMENT study, which focused on Actos in people with type 2 diabetes. HDL, the good cholesterol, is raised while triglycerides are lowered. There is a corresponding small rise in LDL.

TZDs may play a role in preventing pre-diabetes. The DREAM study of more than 5,000 people with pre-diabetes found those taking Avandia reduced their risk of developing type 2 diabetes by 62 percent. However, the high cost and potential for side effects such as weight gain, fluid retention, congestive heart failure, and increased bone loss leading to osteoporosis are big drawbacks.