A class of drugs still taken by millions of people with type 2 diabetes is associated with a higher risk of dying and heart failure than the newer treatment metformin, researchers say.
Sulfonylureas, long a mainstay of diabetes treatment, performed less well than metformin in a study of oral anti-diabetes drugs, but doctors said the findings aren't necessarily a reason to discontinue taking them. Glyburide, glipizide and glimepiride are examples of sulfonylureas.
Metformin, which is sold as Glucophage and other brand names, is already the first-choice therapy for type 2 diabetes, and the findings are in line with new American Diabetes Association recommendations, meaning the results won't change the way patients are already treated.
"This raises some interesting points for other, more specific research, but it won't affect the way we practice medicine tomorrow," said Dr. Robert Scott III, assistant professor of internal medicine at Texas A&M Health Science Center College of Medicine and senior staff cardiologist with Scott & White, Temple, Texas. "Certain diabetes medications may be a little bit more heart friendly than some of the older diabetes medications, but the bottom line is, we can't draw firm conclusions from this."
Other experts agree.
"Metformin is widely believed to exert a favorable cardiovascular effect, and these findings support this observation," added Dr. Steve Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, while pointing out that the study has "important limitations" and should not be considered "proof of differences between various drug therapies."
The new study, appearing in the Dec. 4 issue of BMJ, also found that the diabetes medications Actos (pioglitazone) and Avandia (rosiglitazone) did not seem to raise the risk of heart attack. But Actos was associated with a lower risk of dying than Avandia, indicating Actos might be the preferred choice.
Both drugs belong to the class of medications known as thiazolidinediones.
The hundreds of millions of people around the world who have type 2 diabetes have at least double the risk of dying, largely from cardiovascular disease, than otherwise healthy people.
Because elevated blood sugar can destroy blood vessels and organs of the body, drugs to control blood glucose levels are an important component of diabetes treatment. For years, though, researchers worried that these drugs might up the risk for heart problems in a population already at higher risk for such complications.
In this study, researchers from Imperial College London and other institutions looked at records from 1990 through 2005 for over 91,500 diabetics in the United Kingdom.
Compared to those taking metformin, people taking first- or second-generation sulphonylureas had a 24 to 61 percent higher risk of dying from all causes. Those taking second-generation sulphonylureas had up to a 30 percent increased risk for congestive heart failure.
Individuals taking Actos had a 31 to 39 percent lower risk of dying compared with people taking metformin.
Meanwhile, people taking Avandia (rosiglitazone) had a 34 to 41 percent higher risk of dying than people taking its cousin, Actos (pioglitazone).
"A large difference in outcome between pioglitazone and rosiglitazone has been observed in several other studies. Once again, these authors confirm that rosiglitazone appears to be associated with substantially worse cardiovascular outcomes compared with pioglitazone," Nissen said.
The element of choice is still an important one to consider, one expert pointed out.
"Sometimes diabetes patients can't tolerate certain medicines because of side effects, therefore they're left with taking older medicines that might be associated with an increase of heart attack or heart problems, but when you look at the relative risk of that versus the risk of having uncontrolled diabetes, taking that medicine might be more beneficial for certain patients," Scott said.
Although the study was not funded by pharmaceutical companies, several of the study authors do have ties to different drug companies, including GlaxoSmithKline, which makes Avandia, and Takeda Pharmaceuticals, which makes Actos.