Patients with type 2 diabetes who stop taking GLP-1 drugs such as semaglutide or tirzepatide 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 led by researchers at Washington University School of Medicine in St. Louis. Patients who stayed on the drugs continuously, by contrast, had an 18% lower risk of a major cardiovascular event compared with those on an older diabetes drug class. The findings add weight to a growing body of evidence that the heart benefits of GLP-1 drugs do not persist once a patient stops taking them.
The study is observational, drawn from medical records rather than a randomized trial, so it shows an association between stopping the drugs and rising cardiovascular risk rather than direct proof that discontinuation alone causes it. Researchers used a method called target trial emulation, designed to approximate the comparisons a randomized trial would make when running an actual trial on hundreds of thousands of patients is not feasible.
A three-year study of 333,000 veterans with type 2 diabetes
Researchers tracked 333,687 veterans with type 2 diabetes for up to three years, checking their treatment status every six months. Of that group, 132,551 had been prescribed a GLP-1 drug and 201,136 had been prescribed a sulfonylurea, an older class of diabetes medication used as the comparison group. Across the GLP-1 group, 26% stopped the medication entirely at some point during the study, and another 23% went through a gap of six months or longer before resuming, giving researchers a large enough pool of quitters and re-starters to measure how risk moved as adherence changed. All participants were veterans receiving care through the U.S. Department of Veterans Affairs system, which funded the research and gave investigators years of consistent prescription records to work from, a level of long-term tracking that is difficult to assemble outside a closed health system.
Heart protection erodes within months of stopping
The risk did not appear all at once. According to the study published in BMJ Medicine, a six-month interruption followed by resuming the drug raised cardiovascular risk by 4% to 8% compared with staying on it continuously; a full year off raised that risk to 14%; and two years off pushed it to the 22% figure that separates quitters most sharply from patients who never stopped.
Benefit and harm moved on very different timelines. The 18% cardiovascular reduction from continuous use took the full three-year study period to accumulate, while the risk from stopping showed up within months and kept climbing the longer a patient stayed off the drug. That asymmetry is the study’s central finding: a slow-building protection that a patient can lose in a fraction of the time it took to earn, simply by missing refills or pausing for a few months.
Ziyad Al-Aly, the study’s senior author and a clinical epidemiologist who serves as chief of the Research and Development Service at the VA St. Louis Health Care System, said the pattern reflects more than lost weight loss. “When they stop, it’s not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol,” Al-Aly said, adding that many patients quit within a few months because of cost, side effects or supply shortages rather than a doctor’s recommendation.
Restarting the drug does not fully rebuild it
Resuming a GLP-1 drug after a gap did not restore the same level of protection patients had before they stopped, according to the study, which found that lost cardiovascular benefit only partially came back even after treatment resumed. Al-Aly argued the finding should change how clinicians think about the drugs, saying, “Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right — not an afterthought.”
The study adds to a run of 2026 research pointing the same direction. Reporting on the broader evidence base notes an August analysis of Danish semaglutide users in JAMA Network Open and a May review in Nature Reviews Endocrinology reached similar conclusions about discontinuation and rebound risk, though none of those papers used the veteran population or the 22% figure that anchors the Washington University analysis.
What the study does not resolve is what should happen next for the patients most likely to quit. Cost, side effects and shortages, not medical advice, drive most of the discontinuations Al-Aly’s team tracked, and neither the study nor the health systems that rely on it have yet built the infrastructure to keep more patients on the drugs long enough to hold on to the protection continuous use provides. Al-Aly’s team stopped short of recommending a specific fix, framing the adherence gap as a problem for clinicians and insurers to solve rather than one the data alone could settle.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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