Metformin Affects Hearts of Men and Women Differently

The oral diabetes medicine metformin affects the hearts of men and women differently, according to new research from the Washington University School of Medicine in St. Louis. Metformin is the most widely used diabetes drug in the world, with more than 61 million prescriptions being filled in the United States alone in 2012.

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Cardiovascular disease is the leading cause of death in people who have diabetes. To determine whether sex has an effect on the heart’s response to diabetes treatments, researchers randomly assigned 43 women and 35 men with Type 2 to one of three groups: The first group received metformin alone, the second received metformin plus rosiglitazone (brand name Avandia), and the third received metformin plus Lovaza, a type of fish oil prescribed to lower blood fats known as triglycerides.

At the start of the study and at three months in, each participant had a PET scan to evaluate oxygen levels, blood flow, and glucose and fatty acid uptake in the heart; blood tests to measure glucose and free fatty acid levels; and an echocardiogram to evaluate heart function.

Blood glucose levels were well controlled in all three groups. When the groups were compared without separating men and women, no differences were seen in heart metabolism. But when the participants were separated by gender, it became clear that the medicines had different, and sometimes opposite, effects on cardiac function.

The biggest difference between men and women was seen in the group taking metformin alone. The drug appeared to improve heart function in women, but it caused the hearts of men to burn less sugar and more fat — a shift that can eventually cause changes in heart muscle, leading to heart failure.

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

Taking rosiglitazone along with metformin seemed to lessen some of the negative cardiac effects of metformin seen in men. In women, who were already benefiting from the metformin, adding rosiglitazone improved heart function further by reducing the heart’s dependence on burning fat. The addition of Lovaza to metformin did not significantly affect heart function in either direction for men or women.

Although the study was small, Gropler noted, it was quite rigorous in the methods it used to analyze heart metabolism.

The differing reactions of men and women may at least partially explain the conflicting data on some diabetes medicines, since the proportion of men and women in clinical trials may impact whether a drug is found to be safe and effective. As individualized approaches to diabetes therapy become more popular, there should be further investigation into gender-related responses to medicines, the researchers suggest.

Limitations of the study include its small size, as well as an early termination of the rosiglitazone group due to restrictions imposed by the Food and Drug Administration on the use of this medicine (since lifted).

For more information about the research, read the article “Diabetes Drugs Affect Hearts of Men, Women Differently” or see the study’s abstract in the American Journal of Physiology: Heart and Circulatory Physiology.” And to learn more about metformin, click here.

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