Stopping Ozempic or Mounjaro raises heart attack risk 22% within two years

People who stop taking semaglutide drugs such as Ozempic and Wegovy, or tirzepatide drugs such as Mounjaro and Zepbound, face a 22% higher risk of heart attack, stroke or death within two years of quitting, according to a study of more than 333,000 U.S. veterans with type 2 diabetes. The finding comes from a Washington University School of Medicine-led team that tracked patients’ cardiovascular outcomes for up to three years after they started the drugs.

The added risk does not wait until the two-year mark to appear. Researchers found it building within months of a patient stopping the medication entirely, then climbing steadily the longer the gap lasted, in a pattern that tracked how long someone had been off the drug far more closely than it tracked how much weight they had regained.

A three-year VA study tracked 333,687 patients

Yan Xie, Taeyoung Choi and Ziyad Al-Aly, working out of Washington University School of Medicine and the VA St. Louis Health Care System, published the analysis in BMJ Medicine, drawing on Department of Veterans Affairs health records collected between 2017 and 2023. Their study team compared 132,551 patients newly prescribed a GLP-1 drug against 201,136 prescribed a sulfonylurea, an older class of diabetes medication that lowers blood sugar without the same cardiovascular track record, and followed both groups for up to three years. Using a comparator drug rather than a placebo group let the researchers isolate what changed specifically after a patient stopped a GLP-1, instead of just comparing treated patients to untreated ones.

Al-Aly, a clinical epidemiologist who also serves as chief of the Research and Development Service at the VA Saint Louis Health Care System, led the analysis as senior author. All 333,687 patients had type 2 diabetes at enrollment, which let the researchers isolate cardiovascular outcomes tied to the drug itself rather than to weight loss alone, and the veteran population gave them years of consistent electronic health records to draw on.

Risk climbs the longer patients stay off the drug

Veterans who interrupted treatment for six months and then resumed it still carried a 4% to 8% higher risk of a major cardiovascular event compared with patients who never stopped, a gap the authors called modest but real. That risk grew to 14% after a full year off the medication and reached 22% two years after discontinuation, according to the study’s reported figures.

The pattern held regardless of how much weight a patient had regained, the researchers noted, since the cardiovascular decline tended to show up before most of the lost weight came back.

Staying on therapy continuously cut risk by 18%

Patients who remained on a GLP-1 drug continuously for three years had an 18% lower risk of heart attack, stroke or death than those taking a sulfonylurea the whole time. Even patients who used a GLP-1 drug for two to two-and-a-half years before stopping kept a 7% to 15% risk reduction, suggesting some protection lingers for a while after treatment ends, though not indefinitely and not enough to offset a longer gap.

Patients who paused treatment and later resumed it fell somewhere in between: on average, they kept about a 12% risk reduction compared with never taking a GLP-1 drug at all, well short of the 18% reduction among patients who never stopped. That gradient — full continuous use protecting more than interrupted use, which in turn protects more than permanent discontinuation — is what led the authors to describe cardiovascular protection as something that has to be maintained rather than banked.

GLP-1 drugs are thought to protect the heart through several channels beyond blood sugar control: reducing inflammatory markers such as TNF-alpha and IL-6, easing blood pressure and cholesterol, and improving blood vessel function, according to a mechanism review published in the peer-reviewed literature. Stopping the drug appears to remove those effects at close to the pace they arrived, which the study’s authors say may explain why the risk curve reverses so fast.

Al-Aly calls the drop-off a blind spot in GLP-1 care

“There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop,” Al-Aly said, describing the gap the study set out to measure.

“Many quit after a few months because of cost, side effects or shortages. When they stop, it’s not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol,” Al-Aly said. The national shortages that hit tirzepatide and semaglutide during years of surging demand have since eased — the FDA confirmed tirzepatide’s shortage resolved in December 2024 and semaglutide’s in February 2025 — but cost and side effects such as nausea remain common reasons patients stop on their own.

The study, which was distributed again in a ScienceDaily summary months after its original publication, has continued circulating because the underlying question has not gone away: millions of patients now cycle on and off these drugs for reasons that have little to do with medical advice.

“Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right,” Al-Aly said — a recommendation that puts the burden on doctors to plan for the cost and supply problems that push patients to stop before a replacement plan is in place.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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