Diabetes Medications & Heart Disease: Are You Getting the Care You Need?

If you have type 2 diabetes and cardiovascular disease, it’s a good time to talk to your doctor.

Older Man at Doctor's OfficeSome drugs designed for blood sugar control have been shown to have cardiovascular benefits, too.

A number of newer diabetes medications have been found to prevent heart attacks and strokes, slow heart failure, and prevent death.  The result—updated clinical guidelines on treatment from both the Joslin Diabetes Center1 and the American Diabetes Association.2

All of this is vitally important  since people with diabetes have two to four times the likelihood of developing cardiovascular disease than a person without diabetes, according to the American Heart Association.3

Why is diabetes such a risk factor? Over time, high blood sugar can damage your blood vessels and heart, putting you at greater risk of having a heart attack or stroke, the most common causes of death for adults with diabetes. But even if your blood sugar is well managed, other factors, including high blood pressure, obesity, unhealthy cholesterol levels, lack of physical exercise, and smoking, can lead to heart problems.

While lifestyle changes–managing your glucose, cholesterol and blood pressure along with eating a healthy diet and getting regular exercise—remain a priority, if you already have high cardiovascular risk factors or cardio-complications, adding or changing medications may help.

Good News

In 2008, the Food and Drug Administration (FDA) required glucose-lowering diabetes drugs to undergo testing to prove that they weren’t negatively impacting heart health. But when the results came back, they showed that some of the drugs designed for sugar control actually improved cardiovascular outcomes.

“It was a shocker,” said Betul A. Hatipoglu, MD, an endocrinologist at the Cleveland Clinic. “I am so grateful that we looked into this. Who doesn’t want to have medication that not only improved glucose but has cardiovascular benefits?”

This surprising result has led a new era where a number of “very exciting new cardiovascular trials have been completed using the drugs that were designed for blood sugar control,” said Om Ganda, MD, medical director of the Lipid Clinic at Joslin Diabetes Clinic and associate clinical professor of medicine, Harvard Medical School.

“No one believed it because there were no good studies showing that diabetes control itself can have a major impact on cardiovascular outcomes,” said Dr. Ganda. “There had been some evidence that lowering blood sugar lowered the risk of cardiovascular disease, but they had been done a long time ago. Today, there are certain drugs that have additional properties that make people with diabetes have fewer cardiovascular complications, including heart attacks and strokes.”

For now, the majority of studies looked at individuals who had a very high risk of cardiovascular disease, said Dr. Hatipoglu. “Patients had overt cardiovascular disease, strokes or heart attacks.”

While several studies have shown that these drugs reduce cardiovascular risks and death, it’s not yet completely clear how they work, said Dr. Ganda.

“We have some ideas about it, but it’s not one simple mechanism. There are a number of mechanisms,” he says. “We know that lowering blood sugar itself is a link between small vessel disease (that can cause retinopathy, etc.) but not with cardiovascular disease that affects large vessels such as those found in the heart.”

Thwarting Heart Disease: Blood Sugar Drugs With  Cardiovascular Benefits

So, what are these drugs? They include: 

GLP-1 agonists: These injectable drugs work by helping your pancreas produce more insulin when your blood sugar is high. Drugs that have produced cardiovascular benefit include the FDA approved liraglutide (Victoza) and semiglutide (Ozempic). Benefits include a reduction in heart attacks and strokes. Liraglutide reduced major cardiovascular events in two large clinical trials in patients with high cardiovascular disease or a high risk of cardiovascular disease.4

SGLT2 inhibitors: These oral drugs lower blood glucose by preventing the kidneys from reabsorbing glucose, instead, sending the glucose out of the body through the urine. They also have modest benefits on weight and blood pressure and do not increase the risk of low blood sugar.

This class includes empagliflozin (Jardiance),5 canagliflozin (Invokana), dapagliflozin (Farxiga) and most recently, ertugliflozin (Steglatro). So far, only Jardiance has been approved by the FDA, but studies have shown that Invokana has a similar effect in reducing major cardiovascular events, heart failure, and death in clinical trials. Trials are underway for Farxiga and Steglatro.

Older drugs may also show some benefit:

Metformin: This first-line type 2 diabetes drug reduces the amount of glucose produced by the liver, which helps lower blood pressure.

The United Kingdom Prospective Diabetes Study (UKPDS), published in the Lancet in 1998, drew a link between metformin use and cardiovascular benefits.6  And in a small 2013 study, researchers found that metformin reduced cardiovascular risk seemingly independent of lowering blood glucose concentration in patients without type two diabetes. 7

“I wouldn’t necessarily use metformin for cardiovascular protection since there are other drugs that are approved for secondary use that may have more benefits,” said Dr. Hatipoglu. “But there is some information that it might be beneficial.”

Thiazolidinedione (TZD): The TZD drug pioglitazone reduced macrovascular events in the PROactive (PROspective pioglitAzone Clinical Trial in macroVascular Events) trial,8 but the benefits were counterbalanced by an increase in heart failure. However, the drug did show very strong stroke prevention even in patients who were not diabetic, said Dr. Hatipoglu.

“I don’t often use TZD’s as an option, mainly because they can cause weight gain, water retention, and some bone loss,” she says. “I don’t like those side effects, but I will go for one of these agents if I need another to add. It isn’t my first choice.”

Hypoglycemia Concerns for Some 

Drugs that can cause low blood sugar should be used carefully in patients with heart issues, says Dr. Hatipoglu.

“It’s not widely accepted but some sulfonylurea studies show that they might not be a great agent for cardiovascular disease. It’s not a reason to stop them but any agent which runs the risk of hypoglycemia should be avoided in patients with cardiovascular disease because it can cause arrhythmia and even death,” she said.

“Anytime you are adding a medication like a sulfonylurea or even insulin to a patient’s regimen, it needs to be titrated very carefully. Patients must be sure to test their glucose carefully, understand what hypoglycemia is and know how to treat it.”

“There isn’t one single medication that I would say, my goodness this is evil, don’t use it. But there are some cautionary things to be aware of,” she said.

The Future

So far, most patients in the trials for the newer drugs had established cardiovascular disease, so it’s unknown whether the drugs can prevent initial cardiovascular problems. But at the upcoming meeting of the American Heart Association, members will hear the results of a new study that treated 17,000 people with a drug from the SGLT2 inhibitor class. Ten thousand of the participants did not have a preexisting cardiovascular disease

“It will be a highlight if it works,” said Dr. Ganda.

Among the current drawbacks of the new drugs is that they can be expensive and since they are new, not enough is yet known about possible long-term side-effects.

“For people who already have high cardiovascular risks and who have had heart attacks or strokes, many insurance companies will pay for these newer medications. But for people who are poor, they may have very restricted coverage,” noted Dr. Ganda.

“Obviously the best option is the prevention of development of diabetes,” said Dr. Ganda. “We have the means to prevent diabetes, but the general public is often not able to lose weight and not able to follow diet and exercise plans. On top of that, one out of four people in the US are not even aware that they have diabetes,” he says. 

With or without the drugs, Dr. Ganda wants all patients to stay aware of their own health.

“The most important thing is to know your A1C and measure your blood glucose regularly, especially if you’re not getting acceptable numbers, to keep your blood pressure in control 140/90 or 130/80 for people at risk for heart disease and to keep your LDL (bad cholesterol) as low as possible.”

Both doctors are eagerly anticipating studies on patients who have never had a heart attack or stroke to see if these medications can prevent a first cardiovascular event.

“I’m looking forward to even newer agents, so we have more tools to offer our patients who might not be able to use or tolerate these medications,” says Dr. Hatipoglu.

“It never hurts to have more options.”

 

Updated on: November 1, 2018
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