GLP-1 receptor agonists, the drug class that includes Ozempic, Wegovy, Mounjaro, and Trulicity, have become one of the biggest stories in medicine. They help people lose weight, manage blood sugar, and lower their risk of heart attack and stroke. Around one in eight American adults has now reportedly taken one.
But here’s the part the headlines don’t always cover: a lot of people stop. Some can’t tolerate the side effects, others can’t afford the ongoing cost, and many simply assume they can pause once they’ve hit a goal. New research published in BMJ Medicine in March 2026 looked at what happens to your heart when you do, and the findings are worth paying attention to.
The Study, in Plain English
Researchers at the US Department of Veterans Affairs followed more than 333,000 adults with type 2 diabetes for up to three years. About 132,000 had started a GLP-1 drug, and roughly 201,000 had started a sulfonylurea (an older diabetes drug used here as a comparison group). Using a method called target trial emulation, the team modelled what would have happened under 16 different treatment scenarios: continuous use, partial use followed by stopping, and various patterns of stopping and restarting.
The outcome they tracked was “major adverse cardiovascular events”: heart attacks, strokes, and deaths from any cause.
What They Found
The cardiovascular benefit builds up over time. It isn’t an instant payoff. Compared with the older diabetes drug, people who took a GLP-1 for six months, one year, or even 18 months (and then stopped) showed no meaningful reduction in their three-year risk of heart attack, stroke, or death.
Real benefit kicked in around the two-year mark. People who stayed on treatment for two years saw a 7% reduction in risk. At 2.5 years, it climbed to 15%. And those who stayed on continuously for the full three years saw the biggest payoff: an 18% reduction in major cardiovascular events compared with the sulfonylurea group.
Stopping appears to undo the protection. Compared with people who kept taking their GLP-1, those who stopped for six months had a 4% higher risk. One year off raised the risk by 14%. Two years off pushed it to 22% higher.
Interruptions matter too. Even temporary breaks (stopping for a while, then restarting) were linked to higher cardiovascular risk in a dose-dependent way. The longer the gap, the worse the outcome.
The researchers also looked at “proportion of days covered”, basically how much of the follow-up period each person was actually on the drug. The pattern was a smooth gradient: more days covered, lower risk.
How Common Is Stopping?
Very. About 26% of GLP-1 users in the study discontinued treatment entirely, and another 23% had interruptions. Most of these stops happened in the first year. The median person who discontinued had been on the drug for just over seven months.
This matches earlier research showing discontinuation rates anywhere from 36% to 81% within the first year of starting. The reasons usually come down to side effects (mainly gastrointestinal), cost, and the perception that the drug isn’t working, sometimes long before the cardiovascular benefits would have had time to accumulate.
Why Would Stopping Reverse the Benefits?
The mechanism isn’t fully nailed down, but the leading explanation is that the things GLP-1 drugs improve (weight, blood sugar, blood pressure, lipid profile, inflammation) tend to bounce back when the drug is stopped. Weight regain after discontinuation is well documented, and inflammatory markers and other cardiometabolic measures appear to follow suit. If those underlying drivers of cardiovascular disease return, it makes sense that the protection would too.
What This Means in Practice
A few practical takeaways:
The cardiovascular benefit of these drugs isn’t something you can bank in six months and walk away with. If heart protection is part of why you or your doctor chose a GLP-1, the data suggest treatment needs to be sustained, likely well past the first two years, to get the payoff.
Stopping isn’t risk-free, even temporarily. The study found a measurable increase in risk after just six months off treatment. That’s worth raising with a clinician before deciding to pause.
Side effects and cost are real barriers, and they’re worth addressing directly rather than just stopping. Slower dose titration can ease gastrointestinal symptoms for many people. And in the US, where out-of-pocket costs are a major reason people stop, talking to a prescriber or pharmacist about coverage options or alternative formulations may be worth the effort.
The Caveats
This was an observational study, not a randomised trial. So while the methods (target trial emulation, marginal structural models, extensive covariate adjustment) are about as rigorous as observational research gets, residual confounding is always possible. The cohort was also drawn from US veterans, who are older and mostly male, so the absolute numbers may not translate perfectly to other populations. And the researchers looked at the GLP-1 drug class as a whole rather than comparing individual drugs against each other.
Still, with hundreds of thousands of participants and consistent findings across more than a dozen sensitivity analyses, the broad pattern is hard to dismiss: with GLP-1 drugs, continuity matters.
The Bottom Line
GLP-1 receptor agonists offer real cardiovascular protection, but the protection is earned slowly and lost relatively quickly. For anyone taking them, or thinking about taking them, the question isn’t just “does this drug work?” It’s “can I stay on it long enough for it to work?” That’s a conversation worth having with your healthcare provider before, not after, you decide to stop.
Based on: Xie Y, Choi T, Al-Aly Z. Glucagon-like peptide 1 receptor agonist discontinuation and risks of major adverse cardiovascular events in adults with type 2 diabetes: target trial emulation. BMJ Medicine 2026;5:e001234.
