Cardiovascular disease caused by atherosclerosis and heart failure are common conditions in people with diabetes. Brendan M. Everett, MD, MPH, a general and preventive cardiologist, explains when to refer patients to a cardiologist, best practices for treating CVD, the risks and benefits of medicines, and research questions to be answered.

Q: What types of cardiovascular disease (CVD) are most common in people with diabetes?

A: The prevalence of any heart condition is more than twice as high in people with diabetes than in people without diabetes (24.2% vs. 10.3%, according to the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey). The type of CVD most common in people with diabetes is atherosclerotic heart disease—plaque-induced narrowing of the arteries in the heart. Atherosclerotic heart disease includes coronary heart disease (also sometimes called coronary artery disease), in which the arteries of the heart cannot deliver enough oxygen-rich blood to the heart. Atherosclerosis can also occur in arteries that supply blood to the brain, which can lead to stroke, and to the legs and other parts of the body, which can cause peripheral artery disease.

Increasingly Heart failure is also important. It refers to the inability of the heart, kidneys, and blood vessels to provide for the body’s metabolic and oxygen needs. People with heart failure may have symptoms like shortness of breath and leg swelling because fluid is retained.

Q: When should a person be referred to a cardiologist? How can referring health care professionals work effectively with cardiologists?

A: Referrals vary, depending on the comfort level of the health care professional caring for the person with diabetes. Certainly, patients with established CVD should see a cardiologist. That includes anyone who’s had a heart attack or stroke. Anything that suggests a disorder within the cardiovascular system—such as chest pain with exercise or a positive stress test—should merit a referral. The cardiologist can help the referring health care professional decide how serious a condition is and how much ongoing care the person needs from a cardiovascular specialist.

There are areas of overlap for health care professionals who treat people with diabetes and those who care for people with CVD. For example, both can explain the benefits and risks of specific medicines for people with diabetes and CVD. If the referring health care professional knows a trusted cardiologist, it never hurts to send a patient to see that specialist. As a cardiologist, sometimes I have time that a primary health care professional doesn’t to give a patient advice about approaches to diet and exercise.

It can be difficult for health care professionals to collaborate with each other because we’re all inundated with information and communication. We use an electronic health record that sends consultative notes to an in-basket. The problem is that health care professionals can be so overwhelmed with messages that it’s sometimes hard to tell what’s urgent or important. So, it’s really a question of how both health care professionals can best communicate and collaborate. The goal is for patients to get the best care.

Q: What are the best practices for treating people who have both diabetes and CVD?

A: This is a nuanced topic because not all CVD is the same, just like not all diabetes is the same. Generally, we start with diet, exercise, and smoking cessation. If the patient has coronary heart disease, cardiologists first assess low-density lipoprotein (LDL) cholesterol, blood pressure, and the medicines being taken. How aggressively can we drive down cholesterol and blood pressure? What’s the right mix of antiplatelet medicines like aspirin? Are there other therapies, such as those that treat inflammation, or specific therapies that treat both diabetes and CVD that the patient should be taking?

The benefits of statin therapy in reducing LDL cholesterol and atherosclerotic CVD are well established. Most people with diabetes and CVD should take a high- or moderate-intensity statin. Health care professionals should note that statins can cause small increases in blood glucose levels, but those effects are quite small and are dwarfed by the benefits of preventing heart attack and stroke.

Recently, we have focused on therapies for managing both diabetes and CVD. We think about sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists because of their benefit for cardiovascular outcomes in people with diabetes. As a cardiologist, I often initiate one of these medicines if I think it’s required. For example, for people with heart failure, we often prescribe an SGLT2 inhibitor to reduce the risk of a hospital stay and death, in addition to other medicines such as antihypertensives and low-dose aspirin. Recent studies of patients with one type of heart failure suggest they feel better when taking a GLP-1 receptor agonist.

We try to provide the best care we can based on clinical guidelines published by professional societies like the American Heart Association and the American College of Cardiology(PDF, 2.1 MB) . Many of my colleagues read the Standards of Care published by the American Diabetes Association, too. Another helpful resource is the 2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients with Type 2 Diabetes.

Q: How effective are SGLT2 inhibitors and GLP-1 receptor agonists in managing CVD in people with type 2 diabetes? What are the goals of using these medicines in people with diabetes and CVD?

A: Certain SGLT2 inhibitors and GLP-1 receptor agonists have led to a profound change in our ability to treat people with diabetes, heart disease, or obesity, or a combination of these conditions. The U.S. Food and Drug Administration originally approved these medicines to lower blood glucose levels in people with type 2 diabetes. Since then, their use has expanded to help improve cardiovascular outcomes and to aid weight loss for people with obesity or overweight. Their efficacy in treating heart disease is such that many cardiologists are comfortable using them because they want to help their patients avoid a heart attack or a hospital stay for heart failure. The use of these medicines has skyrocketed because of clear clinical benefits—for people with and without diabetes. The goals of prescribing these medicines are to help people live longer and feel better.

There have been issues about the medicines being available and affordable, but hopefully these problems will start to ease over the next few years.

It's important to remember that these therapies should be used regardless of the patient’s starting blood glucose or hemoglobin A1C levels. They offer cardiovascular benefits that are well beyond their effects on glucose lowering.

Unfortunately, these novel therapies aren’t approved for people with type 1 diabetes. It’s challenging that there aren’t more and better therapies for managing blood glucose and CVD for them. When I have patients with type 1 diabetes in my clinic, I focus on managing blood pressure and cholesterol and decide if there’s a role for antiplatelet therapy like aspirin. We want to prevent long-term complications like heart attack, stroke, and peripheral artery disease. I leave managing glucose for people with type 1 diabetes to diabetes care professionals because that’s where they excel.

Q: What are the risks of using SGLT2 inhibitors and GLP-1 receptor agonists?

A: For SGLT2 inhibitors, the most common side effect people worry about is genital fungal infections and urinary tract infections. At times, people may complain of feeling dehydrated. A lot of this depends on the person’s blood glucose levels when starting the medicine. If their blood glucose levels are in their target range, then some of these side effects are less common. Health care professionals should ask their patients to alert them if they think something is wrong. Then they can tackle the problem together.

A less common but important risk of SGLT2 inhibitors is diabetic ketoacidosis. If a person has had an episode before, health care professionals must be more careful, and they may want to avoid this class of medicines.

For GLP-1 receptor agonists, the most common side effect is usually nausea, which can be managed by slowly increasing the dose of the medicine. People often take a long time to get up to the goal dose or don’t ever quite get there. Finding the dose they can tolerate often gives them many of the benefits, such as improved blood glucose levels, weight loss, lower blood pressure, and a lower risk of heart attack and stroke.

More serious side effects include worsened diabetic retinopathy. GLP-1 receptor agonists should not be prescribed to people taking another GLP-1 receptor agonist or a DPP-4 inhibitor. They should also not be prescribed for people with a personal or family history of medullary thyroid cancer, pancreatitis, or gastroparesis.

Both SGLT2 inhibitors and GLP-1 receptor agonists have the added benefit that they don’t cause hypoglycemia if the patient isn’t taking insulin or a sulfonylurea. If the patient is taking insulin or a sulfonylurea, we recommend reducing the dose of those medicines when starting the new SGLT2 inhibitor or GLP-1 receptor agonist.

Q: What questions on this topic are researchers trying to answer?

A: Many SGLT2 inhibitors and GLP-1 receptor agonists have been shown to be effective at reducing adverse cardiovascular outcomes, but they’ve been compared to placebo and not to one another. Also, some health professionals argue that people with diabetes and CVD should take both kinds of drugs, as opposed to just one, but we don’t have a lot of data on that, either.

I’ve had the good fortune to be working with an endocrinologist colleague, Deborah Wexler, MD, MSc, on a large clinical trial, PRECIDENTD, to compare SGLT2 inhibitors and GLP-1 receptor agonists in people with type 2 diabetes and atherosclerosis. We want to know if one type of drug is more effective than the other in preventing adverse cardiovascular and kidney outcomes. Participants are randomly assigned to take an SGLT2 inhibitor or a GLP-1 receptor agonist. Once assigned, they can take any of the medicines in that class that have shown cardiovascular efficacy. We can’t include people with heart failure because they should be taking an SGLT2 inhibitor, and we can’t randomly assign them to a treatment group that might not include an SGLT2 inhibitor.

What approaches have you taken to treat CVD in people with diabetes? Share with us below in the comments.