One in 8 American adults now takes a GLP-1 drug to manage diabetes or obesity. While both clinical and real-world results have shown these medications can improve heart health, new research has found a downside: People who stop taking them quickly lose these improvements and may be at an increased risk of heart attack, stroke, and even death compared with people who stay on them consistently.
“When people are on these medications, all these beneficial things happen: Blood pressure gets better, cholesterol goes down, insulin resistance goes down,” says the senior study author, Ziyad Al-Aly, MD, a clinical epidemiologist at WashU Medicine and the chief of the research and development service at the VA Saint Louis Health Care System, both in Missouri.
“When they stop taking the medication, they’re exposing their body to whiplash that stresses the heart and undoes a lot of those cardiovascular benefits,” Dr. Al-Aly says.
Here’s what the study found, plus what doctors want people with a history of heart health issues to keep in mind before starting one of these medications.
Pausing GLP-1 Therapy Led to Consequences
People who stayed on their GLP-1 medication continuously had an 82 percent lower risk of cardiovascular events like heart attack, stroke, or death during the three-year study period than those who took a sulfonylurea.
But those who stopped or paused GLP-1s for six months had a significant increase in risk of major cardiovascular events.
They also had a 4 percent higher risk of cardiovascular issues than those continually on a sulfonylurea. That risk differential increased to 14 percent a year after they stopped a GLP-1, and rose to as much as 22 percent after two years off the medication.
“Even brief periods of discontinuations or interruptions might progressively erode and could ultimately reverse this protection, increasing the risk of cardiovascular events,” the researchers wrote.
Heart Protections Are Likely Reversed for a Few Reasons
GLP-1 medications can support heart health in a few different ways. “They work through a combination of many events, including weight loss and improving insulin sensitivity,” says Cheng-Han Chen, MD, an interventional cardiologist and the medical director of the structural heart program at MemorialCare Saddleback Medical Center in Laguna Hills, California. “That leads to benefits in cholesterol levels, lowered bodily inflammation, and other mechanisms that help with heart health.”
Dr. Chen says it makes sense that these benefits would disappear if someone stops taking the medication, especially in the absence of dietary and lifestyle changes that support heart health.
Al-Aly says this reversal may be tied to weight regain, but there’s likely more to it than that. “We’re calling it a ‘metabolic reversal,’” he says. “You already got your body used to less insulin resistance, lower blood pressure, and lower cholesterol. When you stop the medication, you experience that whiplash, which stresses the heart.”
When someone stops taking a GLP-1, cholesterol levels and markers of bodily inflammation can spike, Al-Aly says — and that can be hard on the cardiovascular system.
Going On and Off GLP-1s Can Reduce Potential Heart Health Benefits
Participants who stopped and restarted a GLP didn’t end up getting back to the level of heart protection achieved by people who took the medication consistently. The exact reason for this isn’t clear.
“It’s possible that the study wasn’t long enough to show all the beneficial effects over time,” Chen says.
But Al-Aly says there may be more to it. “What we saw is that it takes people a lot of time to build cardiovascular protection and half the time to undo it,” he says. “What takes people a year to build can be undone within half a year of stopping.”
It’s also possible that the effects of going on and off a GLP-1 are too hard for the body to move past, says Mir Ali, MD, the medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California. “When you get damage caused by inflammation that can result from going off these medications, it can be harder to overcome,” he says.
What This Means for GLP-1 Users
People often go off and on GLP-1 drugs because of cost and lack of insurance coverage. “A lot of people get excited about using these shots, but some people have to dish out $400 a month to keep up. That’s a car payment,” Al-Aly says.
Al-Aly stresses the importance of talking with a healthcare provider about your goals and the ability to maintain these medications once you start them. “These medications are not really meant for the short term,” he says. “If people start on a journey and then stop, they could end up in a worse place.”
If you’ve already started taking a GLP-1 and can’t continue with it, Al-Aly recommends talking with your healthcare provider about options. “You could possibly de-escalate and go to a smaller maintenance dose. Those are often cheaper,” he says. “But the evidence shows that a complete stoppage will undo a lot of the benefits you accrued over time.”
Ali also points out that new medications are coming, too. “We’re hoping these will be cheaper, but that remains to be seen,” he says.
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