Heart benefits fade after stopping GLP-1 medications

A large new study has found that heart risks begin to return as soon as six months after stopping a GLP-1. (Credit: Munro/iStockphoto/Getty Images via CNN Newsource)

One major benefit of taking injected GLP-1 medications is a sizeable reduction in risk for heart attacks, strokes and other heart problems.

However, if people stop taking the medication, those heart benefits are erased.

A large new study has found that heart risks begin to return as soon as six months after stopping the drug and may be almost completely eclipsed as soon as a year and a half after stopping.

The study authors said they believe coming off the drug creates a kind of “metabolic whiplash.”

After stopping, the heart benefits seemed to be reversed more quickly than it took to get them in the first place, said study author Dr. Ziyad Al-Aly, who is a clinical epidemiologist at the Washington University School of Medicine in St. Louis.

“It takes a whole lot longer to build or accrue benefit, and then half as much to erase all that benefit,” said Al-Aly, who is also chief of the Research and Development Service at the VA Saint Louis Health Care System.

“For example, what took three years to build — three years of the cardiovascular benefit — was actually erased or undone with just one and a half years of stopping. So generally speaking, it takes twice as much to build the benefit and then half as much to remove that benefit or undo that benefit, or raise that benefit,” he added.

The study, which was published Wednesday in the journal BMJ Medicine, underscores the need to maintain treatment with GLP-1 medications to continue to see their benefits.

Benefits erased within two years

The study took a deep dive into the medical records of more than 333,000 patients with type 2 diabetes who were treated through the Veterans Health Administration.

It did not include people who were using the same kinds of medications for weight loss — the dominant reason people in the U.S. use these drugs.

It compared roughly 132,000 patients had been prescribed GLP-1 medications, to more than 201,000 others who had been prescribed a different type of medication to manage their diabetes, known as sulfonylureas.

The GLP-1s taken by patients in the study included the newer drugs semaglutide, or Ozempic, and tirzepatide, or Mounjaro, as well as any of the older GLP-1s including liraglutide, or Victoza, and exenatide, sold as Byetta and Bydureon BCise, and dulaglutide, or Trulicity.

People who took GLP-1s for an average of three years without stopping saw the biggest heart health benefits. They had about an 18 per cent lower risk of heart attacks, strokes or death compared to people who were on sulfonylureas.

Among those taking GLP-1s, the study further compared those who stopped using the medications to those who stayed on them continuously for three years.

They saw heart risks start to rise again for people who stopped taking GLP-1s within months of going off the drug.

Compared with those who remained on the drug, people who discontinued GLP-1 medication had a four per cent increase in heart risks six months after going off the drug, a 14 per cent increase in risk at a year off the medication, and a 22 per cent increase in risk by the second year off the medication, which meant the benefits they’d seen had virtually been erased by that point.

Evidence for continued use

The degree of benefit reported in the study is very close to that seen in a different trial, called the SELECT study, which looked at the reduction in heart events in people taking semaglutide for obesity. That study reported that the risk of heart attacks, strokes and other major cardiovascular events was reduced by an average of 20 per cent compared with people taking a placebo.

One interesting finding from SELECT, which was published in the New England Journal of Medicine in 2023, was the people saw heart benefits on semaglutide, even if they didn’t lose weight, said Dr. Melanie Jay, who directs NYU Langone’s Comprehensive Program on Obesity.

“It means there’s weight dependent and weight independent effects on the heart,” she added.

It’s not clear exactly how GLP-1 medications improve cardiovascular disease. Many people lose weight on the drugs, and weight loss, which helps reduce inflammation in the body, may be a major driver of heart benefit. The heart also has GLP-1 receptors, so it may be that there’s a direct effect of the drug on heart tissue, Jay said.

Jay said the new study is one of the largest so far to show that the cardiovascular benefits of taking GLP-1 medications don’t persist when people come off the drugs. Jay also praised the study design, which used a large, existing study population with meticulous medical records to try to recreate the original trial design for these medications.

“It’s not like you’re worse off than if you’d never taken it,” Jay said. “You’re just worse off than if you’ve stayed on.”

Many people do discontinue GLP-1 medications. Studies show roughly half of people who start taking GLP-1 drugs will stop within one year. The major reasons for that are side effects like nausea and fatigue and cost – about half the people who stop say they can’t afford to stay on them.

As good as this study is, it leaves some questions unanswered, Jay said. It’s not clear, for example, whether people who come off the drugs, but maintain their weight loss, may continue to see better heart health. Another big question is whether maintenance dosing can stop the backsliding.

“We know even if you maintain your weight on a lower dose or less frequent dose. We don’t know yet, if you maintain the cardiovascular benefit,” she said.

One thing that does seem to be clear is that staying on the drug is important if heart health is a treatment goal.

“This is something you likely need for a longer, long period of time, chronic basis,” Al-Aly said.

He said he’s sympathetic to the fact that many people lose insurance coverage for these medications after they meet their weight loss goals.

Insurers, he said, need to realize that the evidence for these drugs has evolved to show that people need to stay on them to maximize their benefits.

“Stopping has consequences to the heart,” Al-Aly said. “Insurers need to realize that, you know, when they deny these things that actually exposing people to unnecessary risk.”