December 25, 2013
Cardiovascular Effects of Common Diabetes Drugs Vary
by Gender

St. Louis—Men and women may respond similarly to the blood sugar–lowering effect of common diabetes treatments, but cardiovascular effects can vary widely between the sexes, according to a new study.

The study, published recently in the journal American Journal of Physiology—Heart and Circulatory Physiology, said the effect is particularly noticeable with metformin, which has a positive influence on heart function in women but not men. In fact, in males, the drug caused a shift in metabolism that has been linked to a higher risk of heart failure, according to researchers from Washington University School of Medicine in St. Louis.

“We saw dramatic sex differences in how the heart responds to the different therapies," said senior author Robert J. Gropler, MD, professor of radiology. “Our study suggests that we need to better define which therapies are optimal for women with diabetes and which ones are optimal for men.”

The study is significant because patients with diabetes are at higher risk for heart failure, although the mechanisms leading to that outcome are not fully understood.

“It is imperative that we gain understanding of diabetes medications and their impact on the heart in order to design optimal treatment regimens for patients,” added co-author Janet B. McGill, MD. “This study is a step in that direction.”

For the study, investigators evaluated commonly prescribed diabetes drugs in 78 patients, dividing them into three groups: The first group received metformin alone; the second received metformin plus rosiglitazone, marketed as Avandia, and the third received metformin plus Lovaza, a type of fish oil.

No differences in heart metabolism were noted when the three groups were compared without separating by gender. When study subjects were sorted by sex, however, the drugs had very different and sometimes opposite effects on heart metabolism, even as blood sugar remained well controlled in all patients, Gropler noted.

“The most dramatic difference between men and women is with metformin alone,” he added. “Our data show it to have a favorable effect on cardiac metabolism in women and an unfavorable one in men.”

Study authors suggest that may partially explain conflicting data on the safety of some diabetes drugs, such as rosiglitazone, explaining that the proportion of men and women in those studies may be affecting results.

Gropler said the current study found that, in men, metformin caused the body to burn less sugar and more fats, noting that chronic burning of fat by the heart can lead to heart muscle changes seen in heart failure.

“Instead of making heart metabolism more normal in men, metformin alone made it worse, looking even more like a diabetic heart,” he said. “But in women, metformin had the desired effect—lowering fat metabolism and increasing glucose uptake by the heart.”

Results indicated that taking either rosiglitazone or Lovaza with metformin seemed to mitigate some of the negative heart effects of metformin alone in men. Women, who already benefited from metformin, improved heart metabolism further by adding rosiglitazone. Adding Lovaza did not have a strong effect in either direction for men or women.

The Washington University researchers primarily used positron emission tomography (PET) scans to image the heart and measure blood flow, oxygen consumption and fatty acid and glucose uptake by the heart. They also took echocardiograms in conjunction with the PET scans and used stable isotopes to monitor whole-body metabolism and how that influenced the heart.

“If you use standard measurements, you're going to miss the sex differences we observed,” Gropler said. “This may mean we have to do more complex imaging of the heart to better understand which therapies are best for which patients.”

U.S. Pharmacist Social Connect