Even though TZDs have been tested experimentally for other insulin-resistant conditions (e.g., non-alcoholic fatty liver disease, polycystic ovary syndrome, and lipodystrophies), these agents are indicated only for the treatment of type-2 diabetes at this time.


TZDs are not intended for patients with clinical evidence of active liver disease. Rosiglitazone medication is contraindicated for patients with sensitivity to this product or any of its components. Pio-glitazone is contraindicated for patients with diabetic ketoacidosis, hypersensitivity to canadian pioglitazone products, or New York Heart Association class III or IV CHF.

Cost and Economic Burden

Diabetes is the fifth leading cause of death by disease in the U.S., and it increases the risk of complications such as cardiovascular disease, blindness, kidney failure, extremity amputations, neurological disorders, and other chronic conditions. The death toll of patients with type-2 diabetes and its complications in the U.S. exceeds 500 people every day. Although type-2 diabetes can sometimes be treated with diet and exercise, many patients require the addition of an oral antidiabetic agent or a combination of these medications as part of their management program.

For individual countries, the direct health care costs of diabetes range from 2.5% to 15% of annual national health care budgets, depending on the prevalence of the disease in that country and the sophistication of the treatment available.

In strictly financial terms, type-2 diabetes is one of the most costly health problems in the U.S., accounting for more than $40 billion in direct medical costs annually. The total cost of diabetes in the U.S. in 2002 was approximately $132 billion, including $91.8 billion in direct medical expenditures and $39.8 billion in indirect expenditures attributable to lost workdays, restricted activity days, mortality, and permanent disability.

A study conducted in a 500-physician multispecialty medical group owned by a plan with 650,000 members showed that expenditures for diabetes medications and all drugs increased substantially within two health maintenance organizations (HMOs) and continue to represent a larger percentage of total expenditures for patients with diabetes. Nau et al. found that the increased use of multiple drugs for glycemic control, coupled with the increased use of lipid-modifying drugs and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, might have produced much of this increase.

These findings are consistent with a study by Dubois et al. These investigators observed that although expenditures for increased by more than 90% between 1994 and 1997, approximately 73% of this increase was a result of volume factors. However, the shift from low-cost sulfonylureas to more expensive drugs such as TZDs also contributed to the increased expenditures in these two HMOs. Nevertheless, there is evidence that the addition of canadian rosiglitazone to sulfonyl-urea therapy might be associated with a decreased use of medical resources, notably hospitalization and emergency visits. This “add-on” approach, when compared with a monotherapeutic sulfonylurea regimen, has also been related to a decrease in disease-management costs.


Overall, the TZD class of oral hypoglycemic agents presents a number of advantages, primarily (1) decreased insulin resistance, (2) improved glycemic control, (3) reduced triglyceride levels, and (4) elevated HDL-C levels.However, despite the major advantages of TZDs over the older therapies, TZDs sometimes present a number of undesirable but relatively minor side effects, such as water retention (which can be associated with CHF), increased LDL-C levels, and weight gain. These adverse effects can add to the morbidity burden and may affect quality of life.
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Even though TZDs present clinical advantages over other oral hypoglycemic medications, managed care plans will need to examine the cost-effectiveness of TZDs as it applies to their specific plan’s populations. As with other newer drugs, about which effectiveness data are limited, it is important that we accumulate such evidence from observational studies. Future directions in outcomes research will provide more information on the use of the TZDs and their risks and benefits in diverse populations, with their differing baseline risks and behavioral patterns.