Popular GLP-1 medicines (Ozempic and Wegovy) have been used widely for type 2 diabetes and weight control. But a new study suggests that stopping these medicines may have a negative effect on weight regain.
A study of more than 333,000 US veterans with type 2 diabetes found that the cardiovascular benefits of GLP-1 drugs gradually diminished after treatment was interrupted or stopped. After two years without GLP-1 treatment, the combined outcome of heart attack, stroke and death was 22% higher than if they took the medicines.
The research was conducted by scientists at Washington University School of Medicine in St. Louis and published in BMJ Medicine. These findings are particularly relevant in a time when GLP-1 receptor agonists are increasingly used to manage blood sugar and, depending on the medicine and indication, weight and cardiovascular risk.
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However, the 22% figure needs context. The study compared those who stopped treatment with those who continued. It does not mean that stopping Ozempic automatically causes a 22% increase in an individual's pre-existing heart attack or stroke risk.
The study tracked more than 333,000 veterans.
Researchers examined medical records of 333,687 US veterans with type 2 diabetes over up to three years. Of these, 132,551 had been prescribed GLP-1 medicines while 201,136 were prescribed sulfonylureas, another type of diabetes medication.
The researchers examined whether participants continued taking GLP-1 medicines or experienced treatment interruptions. About 26% of GLP-1 users stopped treatment completely during the study, and about 23% had at least six months of treatment delay before restarting.
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The study examined major adverse cardiovascular events such as heart attack, stroke, and death.
People who remained on GLP-1 treatment during the three years showed an 18% lower risk of major cardiovascular events than those who took sulfonylureas. The researchers estimated that this resulted in about four fewer major cardiovascular events for every 100 people over three years.
The cardiovascular benefit was less pronounced for those who stopped taking treatment.
Those who remained on GLP-1 drugs for two years before stopping had a 7% reduction in cardiovascular risk compared to the sulfonylurea group, and those who took the medication for two and a half years before stopping had a 15% reduction. The group that stopped before 18 months did not have a significant cardiovascular risk reduction compared to the comparison group at the end of the study.
Longer treatment gaps lead to higher risk.
The researchers also found that treatment interruptions were associated with a progressive loss of cardiovascular protection.
People who stopped taking GLP-1 medicines for six months and then restarted still appeared to have a lower cardiovascular risk than the comparison group, but the benefit was smaller than that of those who continued treatment without interruption. A six-month interruption was associated with an increase of 4 to 8 percent in cardiovascular risk versus continuous treatment.
The difference was more pronounced for longer periods of time with no treatment.
According to the study, people who discontinued GLP-1 therapy and remained off the drugs for a year had a 14% higher risk of the combined cardiovascular outcome than those who continued treatment. After two years without treatment, the increase reached 22%.
Researchers suggested changes in metabolic factors after stopping treatment could contribute to the findings. As the senior study author Ziyad Al-Aly stated, weight regain may be accompanied by changes in inflammation, blood pressure, and cholesterol after GLP-1 therapy is discontinued.
The study also found that restarting treatment after an interruption could restore some cardiovascular benefit, although the benefit was not as large as with continuous treatment.
Does this mean you should never stop Ozempic?
The findings do not mean that everyone who takes Ozempic or other GLP-1 medicine should continue it indefinitely without medical supervision.
The study targeted US veterans with type 2 diabetes and examined GLP-1 treatment as a class. Rather than testing Ozempic alone, the study included medicines such as semaglutide and tirzepatide. Therefore, the results should not automatically be applied in the same way to every person using a GLP-1 medicine for weight management or another indication.
It is also an observational investigation based on medical records rather than a randomised clinical trial. That is, the data show an association between treatment discontinuation and cardiovascular outcomes, but it cannot be concluded that stopping the medication in and of itself caused each subsequent cardiovascular event.
People may stop GLP-1 drugs for a variety of reasons - side effects, cost, availability or changes in treatment plans. The appropriate decision depends on the person's medical condition, the reason the drug was prescribed, and other risk factors.
Anyone considering stopping Ozempic, Wegovy, Mounjaro, or another GLP-1 medicine should discuss the decision with their doctor rather than stopping treatment on their own.
But the research also underscores a key point for both patients and doctors: the cardiovascular benefits of GLP-1 treatment may not be preserved after stopping the treatment. The longer the treatment interruption, the less benefit was achieved in this study.
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