Features September 2016 Issue

New Diabetes Drugs Offer Heart Protection, Hope to Patients

Empagliflozin and liraglutide may help protect against serious cardiovascular events, while also helping to lower blood glucose.

The search for diabetes medications that help lower blood glucose levels without adding risks to heart health has been going on for years. Ever since studies linked the popular diabetes drug rosiglitazone (Avandia) with greater heart attack risks about 10 years ago, researchers have been developing a new generation of medications to take its place.

Two new drugs have emerged from clinical trials with encouraging results. Empagliflozin and liraglutide have both been shown to reduce the risk of cardiovascular death, while effectively helping to lower blood glucose levels. Empagliflozin is from a class of drugs known as sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Liraglutide is a glucagonlike peptide-1 (GLP-1) agonist. They each work a little differently in the body, but they both may play a role in diabetes management for many people in the years ahead.

“Each new drug for diabetes had to prove it didn’t cause heart problems,” says Cleveland Clinic endocrinologist and diabetes expert Leann Olansky, MD. “These were the first two to show cardiovascular benefits. There may be others in each class becoming available in the next few years.”

Diabetes and Heart Health

The connection between diabetes and cardiovascular health is a powerful one, yet many people are unaware of how much poorly controlled diabetes can raise the risks of heart attack and other cardiac problems.

Diabetes can damage your blood vessels, raising the risk of high blood pressure and other vascular complications. Diabetes may also raise your LDL (“bad”) cholesterol levels, which can further place your arteries under strain. Heart disease and stroke are the leading causes of death for people with diabetes.

Many people with type 2 diabetes are also overweight, a factor that places a burden on your heart and your overall health.

Diabetes is simply an excess of blood glucose (sugar) circulating in your blood stream. The lower the levels of glucose in the blood, the lower the risk of diabetes complications. But Dr. Olansky warns that there is more to controlling diabetes than relying on a pill.

“Lifestyle still matters,” she says. “You should still exercise at least 30 minutes a day, five days a week or more. You have to watch your diet and your weight. Regular exercise and a healthy diet are often worth at least one medication in the treatment of diabetes. So if you don’t like taking so many medications, there is a way to lower that number.”

She urges patients to be proactive through a healthy lifestyle and medication adherence.

“Some patients get motivated when they have had complications,” Dr. Olansky says. “Prevention is so much better.”

Empagliflozin

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New classes of drugs are giving doctors options beyond or instead of metformin to treat diabetes patients.

Empagliflozin first made headlines in 2015, when the results of the landmark EMPA-REG OUTCOME trial were published in the New England Journal of Medicine and presented at the European Association for the Study of Diabetes annual meeting.

The drug is associated with modest weight loss and blood pressure reduction. Dr. Olansky notes that empagliflozin doesn’t much effect on cholesterol, but it does seem to help lower the odds of cardiovascular mortality.

“Rather than prevent events (such as heart attacks), it prevented the events from being fatal,” she explains. “It does have some renal (kidney) protection, but that’s something you’re going to see five to 10 years down the road.”

Liraglutide

Liraglutide also reduces cardiovascular mortality risks, and is one of several drugs in its class that are likely to become routine treatment options for people with type 2 diabetes, Dr. Olansky says.

“These drugs reduce blood sugars more than empagliflozin, but also lower lipids (cholesterol and fats),” she adds.

Liraglutide is also associated with a slight increase in heart rate, so its use in certain patients will have to carefully considered.

How Will the Drugs Be Used

Dr. Olansky says that these drugs are likely to be good options for people taking metformin, but who could use additional help in getting their blood glucose levels under control. The new drugs may, therefore, be second-line treatments.

She also notes that for people who can’t tolerate metformin, these new drugs may be especially helpful.

Patients who have diabetes and kidney disease may benefit from the new drugs. However, the progress of their kidney disease may determine which drug is best.

Dr. Olansky says that liraglutide and other GLP-1 agonists may be used for late-stage renal disease, as well as an initial drug when kidney disease is at its early stages. However, SGLT-2 inhibitors, such as empagliflozin, should be primarily be used for someone with only mild to moderate kidney dysfunction.

Dr. Olansky is hopeful that with more drugs proving their safety and effectiveness in clinical trials, physicians will be better able to find best combination for their patients.

“To have treatments that lower glucose and also reduce cardiovascular mortality is very encouraging,” she says. “This is so important, since patients with type 2 diabetes tend to die of heart disease.”

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