The Case Against The Diabetes Drug Rosiglitazone (AVANDIA)

In September 2006, an orchestrated media blitz proclaimed that the diabetes drug rosiglitazone (AVANDIA) can prevent type 2 diabetes. This finding, hailed as a breakthrough in some reports, was based on the results of a large clinical trial with the catchy acronym DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication).

The DREAM study looked at both the diabetes drug rosiglitazone (AVANDIA) and the heart drug ramipril (ALTACE). The part of the DREAM trial that examined the blood pressure-lowering drug ramipril was eclipsed by the media attention focused on rosiglitazone. Ramipril did not significantly reduce the incidence of diabetes compared to a placebo.

The arm of the DREAM study that focused on rosiglitazone included nearly 5,300 adults. Patients were randomly assigned to receive either rosiglitazone or a placebo over the course of three years. All of the participants were at high risk of developing type 2 diabetes, having shown signs of poor blood-sugar control. The trial found that 280 persons (12 percent) taking rosiglitazone developed type 2 diabetes, compared to 658 (26 percent) of those who took the placebo. In terms of risk reduction, the data indicate that, for every seven high-risk persons prescribed rosiglitazone for three years, one will be prevented from developing diabetes. 

But the researchers also found what they called a “small excess” in non-fatal cases of congestive heart failure with rosiglitazone. This “small excess” amounted to a highly significant seven-fold increase in confirmed cases of heart failure in those taking rosiglitazone compared to the placebo group. In addition, there was an almost significant 37 percent excess in the rosiglitazone group of what the authors called “cardiovascular events composite”, comprised of heart attacks, strokes, cardiovascular deaths, heart failure, the appearance of new angina attacks, and the need for heart surgery such as bypass or angioplasty.

What the press coverage of the DREAM trial did not mention was the fact that a better diet and getting more exercise are very effective non-pharmacological interventions. Indeed, a study published in 2002 found that modifying risk factors with a sustained lifestyle-intervention program was more effective than drugs in preventing type 2 diabetes: the lifestyle intervention lowered the incidence of type 2 diabetes by 58 percent, compared to a 31 percent reduction among those that received drug treatment. The effects were similar in men and women and in all racial and ethnic groups.  

The results of the DREAM trial raise questions concerning the ends of medicine. The people who were given ramipril and rosiglitazone in the DREAM trial were not sick. The participants had elevated blood sugar levels but not to a level that would result in a diagnosis of diabetes; instead, they were labeled with a “new” illness: pre-diabetes.

Expanding the boundaries of an illness such as diabetes has been called “disease mongering,” which was the subject of several recent articles in Public Citizen’s Health Letter.

It is one thing to give a drug with known adverse effects to patients with a serious illness like diabetes but quite another to give the same drug to prevent the disease in otherwise healthy people. If a drug is going to be given to healthy people for disease prevention, it should be held to a high standard, and should be almost totally free from causing serious adverse drug reactions. In 2000, Public Citizen petitioned the Food and Drug Administration (FDA) to add warnings to the professional product labels or package inserts of rosiglitazone and the other drugs in the same family because of safety concerns about heart function, fluid retention, weight gain, anemia, and liver toxicity. The findings of the DREAM trial strengthen the rationale for these concerns.

While interesting, the results of the DREAM trial are not a breakthrough. At present, lifestyle modification is the closest thing we have to a “magic bullet” in the prevention and delay of diabetes. For all the misgivings concerning the difficulties of behavior modification in the areas of diet and exercise, there is no question that, done and sustained, these interventions are more efficacious, probably cheaper, and generally accessible to all. Moreover, their effects can last a lifetime, and they can protect against other diseases as well.

Emphasizing this point, an editorial in the October 7 Lancet following the publication of the DREAM study stated that:

Overall, despite the impressive risk reduction for progression to diabetes, the lack of data on long-term benefits and side-effects, and the high cost of therapy, mean that health-care funders are unlikely to see rosiglitazone as an appropriate agent for individuals with impaired glucose regulation but low absolute cardiovascular risk. Given the prolonged benefits and demonstrable cost effectiveness of intensive lifestyle intervention for people at high risk of diabetes, such interventions should remain the mainstay for the prevention of type 2 diabetes.

What You Can Do

You have a greater likelihood of preventing type 2 diabetes by improving your diet and getting a moderate amount of exercise than by taking a prescription drug. The effects of such a change in lifestyle can last a lifetime.