Arguably the biggest game changer for people with type 2 diabetes happened almost by accident. More than 10 years ago, researchers reviewing dozens of studies found that a group of drugs commonly prescribed to help control blood sugar in people with diabetes had potentially grave side effects. At the time, the drugs known as TZDs (thiazolidinediones) were a go-to treatment for people with type 2 who needed help improving their insulin sensitivity. But that came to an abrupt halt after the review of studies, published in 2007 in The New England Journal of Medicine, detected a link between TZDs and cardiovascular disease. Specifically: People with type 2 diabetes taking TZDs had a 43 percent greater risk of heart attack than those not taking TZDs. What’s more, their chances of dying from a cardiovascular event — meaning heart attack, stroke or heart failure — were elevated.
The Food and Drug Administration (FDA) promptly issued a mandate: Going forward, drug companies must prove that their glucose-lowering drugs wouldn’t damage the heart. Pharmaceutical companies went back to the lab, and their results began to roll out. In a surprising turn, studies showed that not only are the new diabetes drugs safe for the heart; many of them actually help prevent cardiovascular disease. Why is that so important for the 34 million adults in the U.S. living with diabetes? Because they are two to four times as likely to have a cardiovascular event as those without diabetes. In fact, cardiovascular disease is the most common cause of death among people with type 2 diabetes.
“The FDA basically said, ‘If we’re going to approve these drugs for the reduction of glucose, you have to prove they don’t harm the heart,’” says endocrinologist Daniel Stein, M.D., a professor of medicine and principal organizer of the Cardiometabolic Clinic at Montefiore Medical Center in New York City. “Then, lo and behold, all of these drugs not only end up being safe, but they reduce cardiovascular disease outcomes. That was the great surprise.” And a welcome one. “Having diabetes is the equivalent of having known cardiovascular disease,” Stein says. “The risk is identical.”
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Even prediabetes may hurt your heart
The culprit in diabetes’ toll on the heart was long thought to be a lone offender: elevated blood sugar levels. Over time, high blood sugar (glucose) can damage blood vessels and lead to hardening of the arteries, which in turn leads to heart disease. But, as it turns out, there’s more at play. People with diabetes are also more likely to have other conditions that raise the risk for heart disease and stroke, including too much LDL (bad) cholesterol, not enough HDL (good) cholesterol and high triglycerides (a type of fat in the blood). That triad — known as diabetic dyslipidemia — is a deadly combination that puts people with diabetes at risk for cardiovascular disease. Even more concerning: These conditions can develop even before diabetes is diagnosed.
Mounting research suggests the damage may begin at the prediabetes stage. A large review of studies published in a July 2020 issue of BMJ gives credence to what research scientists have suspected for a while: People with prediabetes — meaning their blood sugar levels are higher than normal, but not high enough to be considered diabetes — are at substantial risk of developing cardiovascular disease. In reviewing the 129 studies, which involved more than 10 million people, researchers found that prediabetes was associated with a 15 percent increased risk of cardiovascular disease.
Diabetes drugs with heart-health benefits
Jardiance, Invokana, Farxiga
These three oral meds belong to a class of diabetes drugs called SGLT2 inhibitors. They lower blood sugar by helping the body excrete it in urine. They also act as a diuretic, preventing excess fluid from building up in the body, and that reduces the risk of developing heart failure. “The net result is you’re reducing the glucose level and all the damaging effects of the glucose; you’re losing calories, which helps you lose weight; and because you’re also pulling fluid along with the glucose, it’s acting as a mild diuretic, so it’s good for the heart,” Stein says. “Your blood pressure comes down and there’s less stress on your heart.”
The newest diabetes drug in the SGLT2 inhibitor group does not reduce overall cardiovascular disease in people with type 2 diabetes, according to a new study published in The New England Journal of Medicine. Researchers found that those taking the drug did, however, show a 30 percent lower risk of heart failure than those who didn’t take it.
Victoza, Ozempic, Trulicity
These three injectable drugs fall within a class known as GLP-1 receptor agonists. They work by helping your pancreas release the proper amount of insulin (which helps keep blood sugar levels in check). These drugs also slow the emptying of the stomach, so you feel full longer, which can lead to weight loss.
“It’s not the blood sugar itself that raises the cardiovascular risk, but it’s the other risk factors that are quite prominently associated with prediabetes, just like they are with diabetes,” says Om Ganda, M.D., medical director of the Lipid Clinic at Joslin Diabetes Center and associate clinical professor of medicine at Harvard Medical School.
The risk is especially pronounced in the years immediately following a diagnosis of prediabetes. “The first five years are crucial because that’s when those who are going to get cardiovascular disease may get it,” Ganda says. “If you do nothing about prediabetes — and this has been studied very well — the risk of developing cardiovascular disease is about 10 to 11 percent per year. So in the first five years after diagnosis, your chance of developing cardiovascular disease is about 50 percent.”
Problem is, 88 million adults in the U.S. have prediabetes and 84 percent of them don’t know it. So the overwhelming majority of people with prediabetes are missing out on their best window of opportunity to slow the progression of the disease and the complications that go along with it. “Diabetes affects almost every system in the body — not just the cardiovascular system, but the kidneys, eyes, even the brain,” Ganda says. “The longer it takes to act, the harder it becomes to reverse course.”
Of the new diabetes drugs with cardiovascular benefits, none is approved for use in people with prediabetes. However, new research shows that two drugs, Farxiga and Jardiance, lower the risk of cardiovascular death or hospitalization for heart failure in people with or without diabetes.
But that doesn’t mean these or any of the new drugs are for everyone. (See “Diabetes drugs with heart-health benefits.”) For one thing, they’re still quite expensive, Ganda notes. And, like all drugs, they have side effects, some of them significant. In the end, say experts, the real prescription for both prediabetes and type 2 diabetes — and by extension cardiovascular disease — may not come in a bottle.
“Losing weight and exercise are the two most effective means of reducing risk for cardiovascular disease, particularly if you have prediabetes,” Stein says. “That improves everything: glucose metabolism, blood pressure, cholesterol and triglycerides. Not to mention the fact that if you lose weight, that puts less stress on your bones and joints so you can move around easier — and there’s less stress on your heart.” Plus, these new drugs “don’t work that well unless you’re also on a good lifestyle regimen,” he hastens to add. “A good lifestyle regimen supercharges how beneficial they are.”