Research out today might provide even more of a reason for people to stay on GLP-1 medications like semaglutide, the active ingredient in the drugs Ozempic and Wegovy.
Scientists examined the medical records of veterans taking GLP-1 drugs for their type 2 diabetes. Compared to people on other common treatments, those who remained on GLP-1s for at least two years were less likely to experience major cardiovascular events like heart attacks, they found. Importantly, however, these heart benefits quickly began to fade away in people who discontinued the therapy. The findings highlight the value of these drugs beyond losing weight, the researchers say, while also illustrating why they’re not a short-term fix.
“Stopping GLP-1 drugs has a price,” study author Ziyad Al-Aly, an epidemiologist at Washington University in St. Louis, told Gizmodo.
The cost of stopping
Semaglutide and other newer GLP-1s have substantially improved obesity treatment. Doctors have long cautioned that obesity is a chronic condition and ending the habits that lead to weight loss can often result in regaining it, including GLP-1s.
Most relevant studies have shown that most people who discontinue GLP-1s will regain at least some weight back. But according to Al-Aly, there’s been considerably less attention paid to the more subtle after-effects of ceasing GLP-1 use on the body, the heart included.
Al-Aly is also director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System. For this latest study, he and his team analyzed VA data from over 300,000 people with type 2 diabetes between 2017 and 2023. The team compared the three-year outcomes of roughly 130,000 people prescribed GLP-1s (two-thirds of whom were on semaglutide) to patients prescribed sulfonylureas, another common class of diabetes medication. This data also allowed the researchers to track what happened to people after they discontinued taking a GLP-1.
As other studies have shown, including large-scale clinical trials, people on GLP-1s experienced noticeable heart benefits. Those who stuck with the therapy the entire time were found to have an 18% lower risk of major cardiovascular events compared to the control group. Once people stopped taking a GLP-1, though, their risk of heart problems began rising back up. Within as little as six months, discontinuers started having a higher risk of major cardiovascular events relative to people who stayed on the drugs, the researchers found, a risk that grew larger the longer people were off the medications.
“When people stop these drugs, the weight comes back. Everyone sees that. What they don’t see is the metabolic reversal happening underneath: the inflammation surging, the blood pressure climbing, the cholesterol rising,” Al-Aly said. “And because it’s silent, people don’t realize their risk of heart attack and stroke is climbing after they stop. They find out too late, when they show up to the emergency room with one.”
The team’s findings were published Wednesday in BMJ Medicine.
The importance of maintenance
The team’s study is observational, meaning it can’t directly prove that stopping GLP-1 therapy can lead to heart attacks. VA patients are also disproportionately older, white, and male, which might limit how generalizable these results are.
That said, the researchers did find similar trends when they conducted smaller analyses of women and other demographic groups. They also used a newer statistical approach called target trial emulation for their study, which is intended to strengthen the conclusions that can be made from observational data.
For Al-Aly, the takeaway is simple: People who benefit from these drugs should likely stay on them for the long haul. Unfortunately, that hasn’t always been so easy for users. Some can experience gastrointestinal side effects that are too much of a headache to tolerate; many others might have stopped due to lost insurance coverage or unsustainable out-of-pocket prices. And these lapses could be causing serious consequences in people who keep going on and off GLP-1 therapy, the researchers fear.
“One thing that keeps us up at night is the yo-yo pattern. Millions of people are cycling on and off these drugs because of cost, side effects, and shortages. Every cycle is a round of metabolic whiplash,” said Al-Aly. “We suspect repeated cycling doesn’t just pause cardiovascular protection; it may erase it entirely, or even leave people worse off than if they had never started.”
He added, “For policymakers, the implication is straightforward: a drug can’t protect people who can’t afford to stay on it.”
On the positive side, GLP-1 drugs have become steadily cheaper over time, even for people without insurance coverage. And researchers have been studying ways to curb the side effects and costs of these drugs, which could include spacing out maintenance doses. So hopefully, it’s becoming less of a burden for people who want GLP-1 therapy to stay on it.
Al-Aly and his team have already used their data to explore other questions related to GLP-1s. Earlier this month, for instance, they found evidence that GLP-1s can treat substance use disorders, a potential benefit that’s now being tested in clinical trials. And they plan to keep digging into this topic.
“GLP-1 drugs are the most consequential class of medications to emerge in a generation. They touch diabetes, obesity, cardiovascular disease, kidney disease, and we are now learning that they quiet addiction,” Al-Aly said. “The questions are piling up faster than the answers.”
