Feb. 9, 2005 -- Many people with ailing hearts and diabetes may be missing out on the potential benefits of two common types of diabetes drugs because the drugs are considered too risky for people with heart failure.
A new study shows that the drugs, which include a class called thiazolidinediones (such as Avandia and Actos) and metformin (sold under the names Glucophage, Fortamet, and Riomet), may reduce the risk of death by as much as 13% in people with heart failure and diabetes.
But the FDA and some health groups, including the American Heart Association and American Diabetes Association, warn against using the drugs in this high-risk group.
"We did not find any evidence of significant harm with these agents and found that patients who received prescriptions for them at hospital discharge actually had significantly lower mortality rates," says researcher Frederick Masoudi, MD, MSPH, assistant professor of medicine at Denver Health Medical Center.
But researchers say it's too soon to recommend abandoning current recommendations until further studies can confirm these results.
The FDA advises against using thiazolidinediones in people with advanced heart failure symptoms and requires a "black box" warning -- the agency's strongest type of warning -- in the drug's prescribing information. Package inserts on metformin also warn against the use of this drug in most people with heart failure.
Those warnings stem from concerns about the risk of fluid retention with thiazolidinediones, a common complication of heart failure, and lactic acidosis with metformin. Lactic acidosis is a rare but potentially fatal side effect of metformin that occurs when the tissues of the body do not get enough oxygen.
Researchers say the treatment of diabetes in people with heart failure is controversial, and doctors increasingly prescribe these "risky" drugs to patients with heart failure and diabetes despite those warnings.
Should High-Risk Patients Take the Diabetes Drugs?
Researchers say many doctors may resort to using these drugs in their high-risk patients with heart failure because the drugs have been shown to be effective in getting blood sugar levels under control. Blood sugar control may also be considered more difficult to attain with the alternatives, such as sulfonylureas and insulin injections, in people with advanced disease.
In this study, researchers followed 16,417 Medicare patients with diabetes who were discharged from the hospital after treatment for heart failure.
Researchers divided the patients into groups based on their diabetes treatments and then compared the rates of death and readmission to the hospital.
After one year of follow-up, the study showed that the risk of death from all causes was about 13% lower among the 2,226 patients who received thiazolidinediones or metformin, compared with patients who received neither drug.
Researchers found a small 6% increase in the risk of readmission to the hospital for heart failure among those taking a thiazolidinediones, which researchers say may be a reflection of these drugs' propensity to cause fluid retention. The risk of hospitalization for heart failure was 8% lower among those treated with metformin.
However, there was no difference in hospital admission rates for any cause between those who received the "risky" drugs and those who didn't.
The results appear in the Feb. 8 issue of Circulation: Journal of the American Heart Association.
Too Soon to Change Recommendations
"The study highlights that there may be significant benefits of these drugs in patients with diabetes and heart failure, but we wouldn't advocate practicing outside current recommendations for use of these medications, says Masoudi. "It is a call for randomized trials in populations such as this, which are at very high risk for adverse outcomes from diabetes and from heart failure."
The study also emphasizes the importance of closely monitoring patients on thiazolidinediones.
Robert Rizza, MD, president-elect of the American Diabetes Association, agrees.
"These are provocative data that further supports the need for additional data from the ongoing randomized studies to determine whether these drugs are of value or not," says Rizza.
"These drugs have various actions, some of which may be helpful to people with heart disease, and others which may be harmful to people with heart disease," says Rizza, who is also professor of medicine at the Mayo Clinic College of Medicine in the division of endocrinology, diabetes, nutrition, and metabolism.
"When looking at population-based studies you cannot determine cause from effect, and it's not clear that there was improved survival because the people who had potentially worse outcomes were not placed on the drug because people were concerned about the action of the drug," says Rizza. "That's why additional studies are needed."