FDA OKs Two Medicines for Cardiovascular Disease in Type 2 Diabetes

People with diabetes have two to three times the increased risk for cardiovascular disease and death as those in the general population. Cardiovascular disease also accounts for two out of every three deaths in those with diabetes.

For people with Type 2 diabetes and pre-existing heart disease, the Food and Drug Administration (FDA) recently approved a change in the prescribing information for Jardiance (generic name empagliflozin) and Victoza (liraglutide), indicating they can be used to reduce the risk of cardiovascular disease in this group. Empagliflozin received an indication to only reduce cardiac death. Liraglutide received a broader indication, including reduction of heart attack, stroke, and death.

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FDA Requires heart disease outcomes research

“Until 2008, the FDA approved diabetes medications based only their effects on blood sugar and evidence that they were reasonably safe,” said Steven Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic. “Since then, they have required the performance of additional trials focusing on cardiovascular disease outcomes.”

Most of the research on cardiovascular disease onoutcomes from Type 2 diabetes medications has shown limited or no benefits for the heart. So far, these are the only two exceptions, leading to the changes in prescribing information.

“The FDA staff and their committees thought that the evidence was sufficiently robust to warrant a label claim,” said Nissen. “From the point of view of the patients, this is a big deal because it means after decades of drug development, we have drugs for diabetes that not only lower blood sugar but also reduce cardiovascular morbidity and, in some cases, death.”

A specific group

It is important to note that the label indication affects only a very specific group of people — those with diabetes and current heart disease. The FDA did not address whether these medications help reduce heart complications in those who have risk factors but no known cardiovascular disease.

These decisions were based on the results of the EMPA-REG OUTCOME study for empagliflozin and the LEADER trial for liraglutide. In both cases, only those with Type 2 diabetes and cardiovascular disease were included. The medications were added to the treatment regimens that those in the study were already being prescribed.

The LEADER trial showed a 13% reduction in the composite of death, non-fatal heart attacks, and non-fatal stroke when compared to placebo. EMPA-REG OUTCOME study found that empagliflozin prevented one in three cardiovascular-related deaths and significantly reduced hospitalization in patients with diabetes who had established heart disease.

Type 2 diabetes only

“At present, the evidence only supports a label indication for those with Type 2 diabetes who are already diagnosed with cardiovascular disease,” said Nathan D. Wong, PhD, director of the Heart Disease Prevention Program at the University of California, Irvine, and past president of the American Society for Preventive Cardiology. “What it means is if you have both, adding one of these medications on top of current therapy can further lower your risks of future cardiovascular events.”

The experts agreed that this new indication, while important, should not be construed as limiting the use of the medications in those with Type 2 diabetes who do not have cardiovascular disease. They are still very useful in treating Type 2 diabetes in those with no heart problems.

Although empagliflozin and liraglutide are the only medications so far to receive the FDA’s OK to add reduction of cardiovascular disease as an approved indication, other medicines in the same class may also have similar properties.

Other medicines to follow?

“There are some indications that this may be a class effect in the sodium-glucose co-transporter-2 [SGLT2] inhibitor class, but there is not enough data to date to support this claim,” said Mihail Zilbermint, MD, director of endocrinology, diabetes and metabolism at Johns Hopkins Community Physicians Suburban Hospital in Maryland. “There are a number of trials ongoing to assess the effects of other medications in the SGLT2 class.”

The mechanism that causes these effects is not well understood at this point. Some think it may be related to lowering blood pressure since high blood pressure is a major risk factor for cardiovascular disease. However, the important part is that it works.

“The road to hell is paved with ‘biological plausibility,’” says Dr. Nissen. “When we get a result we don’t understand, everyone has a theory as to why.”

Not magic pills

These are not magic pills that will take away all risk of cardiovascular events in people who take them. You still need to keep up with other cardiovascular disease concerns.

“It is not just taking the medication and keeping blood glucose under control that counts,” said Wong, who serves as a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Leadership Council. “At least as important is making sure that other risks factors for heart disease such as high blood pressure and LDL cholesterol are well controlled and treated according to current guidelines — especially lifestyle issues such as not smoking, keeping a healthy diet, and regularly exercising.”

Should you change medications?

What actions should you take if you have both Type 2 diabetes and heart disease?

“If a patient is already stable on other medications and things are going well, I wouldn’t rock the boat and would continue on the same regimen,” said Zilbermint. “But if you need a medication change and are at risk of heart disease, talk with your doctor about one of these medications as the next one to try if you meet the criteria.”

The decision on how to treat an individual patient is very nuanced and requires a dialog between patient and physician. Weighing both the risks and the benefits for a specific drug is important.

“I do think that we are entering a period of time when you are going to see more people moving toward therapies with a cardiovascular benefit,” said Nissen. “It only makes sense when you have a disease with a significant amount of heart disease.”

Want to learn more about keeping your heart healthy with diabetes? Read “Fight Off Heart Disease With These Five Heart-Healthy Foods,” “Seven Strategies to Boost Heart Health,” and “Lifestyle Habits for Lipid Management.