Stopping Your Ozempic, Even Briefly, May Carry a Hidden Heart Risk

One in eight American adults now takes a GLP-1 drug. About half of them will stop within a year. Most will assume that quitting simply reverses whatever benefits they gained, a straightforward metabolic reset. A large new study published today in BMJ Medicine suggests the reality is considerably more troubling.

Researchers at Washington University School of Medicine in St. Louis followed more than 333,000 US veterans with type 2 diabetes over three years, tracking what happened to cardiovascular risk when patients stopped or interrupted GLP-1 therapy. They found that discontinuing these medications, even temporarily, was associated with a meaningful increase in the risk of heart attack, stroke, and death compared to staying on them continuously.

The study compared 132,551 veterans prescribed GLP-1 drugs, including semaglutide (sold as Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound), against 201,136 prescribed sulfonylureas, a different class of diabetes medication, and checked treatment status every six months for up to three years. Among participants who stayed on GLP-1 medications throughout, the risk of major cardiovascular events was 18% lower than in the sulfonylurea group, roughly 4 fewer events per 100 people over three years. Among those who stopped, that protective advantage began to erode. After two years off the drugs, cardiovascular risk had risen by as much as 22%, largely wiping out what the treatment had achieved.

Restarting helped, but only partially.

That partial recovery is perhaps the most disconcerting detail. The data suggest discontinuation does not simply pause the clock on cardiovascular protection; it leaves something behind. The team attributed the pattern to what they call a metabolic reversal: weight returns, but so do elevated inflammation markers, rising blood pressure, and worsening cholesterol, changes that are not visible the way weight regain is, and that may exert stress on the cardiovascular system before anyone notices.

“There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at WashU Medicine and chief of the Research and Development Service at the VA Saint Louis Health Care System. “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. Weight regain is visible; the metabolic reversal is not.”

Al-Aly and colleagues further found that the longer the gap in treatment, the larger the increase in risk, with a dose-response relationship visible across the six-month assessment intervals. And the problem is not rare: over the course of the study, 26% of GLP-1 users stopped the medication entirely, and around 23% had an interruption of six months or more before restarting. Given that approximately one in eight US adults is currently on these drugs, those percentages represent a substantial number of people accumulating cardiovascular risk that neither they nor their doctors may be tracking carefully.

The study has real limitations, it is observational, its population is predominantly male veterans, and unmeasured confounders cannot be excluded. But the pattern is consistent enough, and the mechanism plausible enough, that the findings add significant weight to the case for treating GLP-1 therapy as a long-term commitment rather than a short course. The drugs are not a cure. They are, apparently, more like a maintenance treatment, one where stopping carries costs that are not always obvious, and not always reversible.

DOI: 10.1136/bmjmed-2025-002150

Frequently Asked Questions

Does this mean no one should ever stop taking GLP-1 drugs?
The study doesn’t go that far, and some people will have legitimate reasons to discontinue, including side effects, cost, or temporary supply shortages. What the findings argue for is a much more deliberate conversation between patients and clinicians before stopping, with an awareness that the cardiovascular benefits built up during treatment can erode faster than expected once the drug is gone.

Why would restarting the medication not fully restore the protection?
The researchers suggest that a period off the drugs allows metabolic conditions to deteriorate, and some of that deterioration may leave a lasting mark on the cardiovascular system. The biological detail behind this “lasting scar” effect is not yet fully characterised, but the pattern in the data, where resumers recovered some but not all of their protective benefit, was consistent across the study’s duration.

Are these findings relevant to people taking GLP-1 drugs for weight loss rather than diabetes?
The study focused exclusively on people with type 2 diabetes, so the results cannot be directly applied to the broader population of people taking these drugs purely for weight management. That said, the metabolic mechanisms involved are broadly similar, and it would be surprising if the cardiovascular consequences of discontinuation were entirely different outside a diabetes context.