People with type 2 diabetes who stopped taking GLP-1 medications had roughly double the risk of heart attack, stroke or death compared with those who continued, according to a new study published in The Lancet Regional Health Europe. The finding was based on records of more than 80,000 Italian patients.
The study, led by Antonio Ceriello, head of diabetes research at Italian hospital IRCCS MultiMedica, analysed electronic medical records from over 300 diabetes clinics in the Italian Association of Clinical Diabetologists database. Patients had started a GLP-1 between 2004 and 2024 and had no established cardiovascular disease.
About four in 100 people who stopped treatment had a heart attack, stroke or died from any cause, compared with about two in 100 who kept using the medication. The risk was higher for those with obesity: a 127% increase in cardiovascular risk after stopping, compared with a 61% increase among those without obesity.
Professor Ceriello said the scale of the association was surprising. "[The strength] of the link has been surprising; almost doubling the risk of [cardiovascular disease]," he told the ABC.
However, several Australian experts not involved in the study urged caution. Clara Chow, academic director of the Westmead Applied Research Centre at the University of Sydney, said the core conclusion "might be misleading" without understanding why participants stopped taking the drugs. About 60 per cent of the 80,302 participants stopped their medication.
“If you've discontinued medication, is it because you feel sick taking it? Or you've got another illness? Or you've got a problem that interacts with it … there's a lot of reasons why people stop treatment,” Professor Chow said. She said the group who stopped had a very high rate of death by any cause, suggesting they could have been sicker than the group who continued.
Brendon Neuen, associate professor of medicine at Royal North Shore Hospital, agreed. "They might have stopped for an appropriate [medical] reason, but those patients are typically sicker, and they're going to do worse," he said.
Because the study was observational, it cannot determine whether stopping GLP-1s directly causes the increased risk or whether those who stopped were already in poorer health. The researchers noted that after people stopped treatment, weight, blood sugar and blood pressure changed only slightly, and there were no significant differences between those who suffered a heart attack, stroke or death and those who did not, suggesting these factors may not fully explain the higher risk.
Professor Ceriello theorised GLP-1 drugs could provide "direct protection" for the cardiovascular system. "If stopped, this protection is lost," he said.
Most participants used older-generation GLP-1s such as liraglutide and dulaglutide. Semaglutide (sold as Ozempic and Wegovy) accounted for only a minor fraction, and tirzepatide (Mounjaro) was not included because it entered the Italian market after the study period.
Natalie Raffoul, head of clinical strategy at The Heart Foundation, said the data was "interesting" but more research was needed. "We know that stopping it comes with consequences and perhaps this study is pointing a spotlight on the fact that these negative consequences might actually be quite significant," she said.
Dr Neuen said that despite the limitations, the study suggested long-term treatment was important for people with type 2 diabetes whose condition was being helped by GLP-1 drugs. He advised patients considering stopping the drugs to talk to a health professional. “There is lots of research going on into how we can effectively use these drugs in the long term,” he said.
Analysis
Why This Matters
- Millions of people with type 2 diabetes use GLP-1 drugs; a substantial proportion stop within the first year, often due to side effects, cost or lack of efficacy. The study suggests that decision may carry significant cardiovascular risk.
- The findings add to growing evidence that the drugs' benefits extend beyond weight and blood sugar control, possibly including direct heart protection. Losing that protection could outweigh the reasons for stopping.
- With GLP-1 use skyrocketing globally, understanding long-term outcomes, both on and off the drugs, is critical for clinical guidelines and patient counselling.
Background
GLP-1 receptor agonists mimic the natural hormone glucagon-like peptide-1 to regulate blood sugar and curb appetite. They have become a cornerstone treatment for type 2 diabetes and obesity in recent years, with some studies also showing cardiovascular and kidney benefits. However, real-world data shows many patients discontinue the drugs within the first year, and coming off them is often followed by weight regain and worsening cardiometabolic risk factors.
Key Perspectives
Professor Antonio Ceriello (lead author): The association between stopping GLP-1s and poorer heart outcomes was "not a complete surprise" but the strength of the link, almost doubling risk, was surprising. He theorises the drugs provide direct cardiovascular protection that is lost when treatment stops.
Professor Clara Chow (University of Sydney, not involved): The core conclusion "might be misleading" without knowing why people stopped. Discontinuation may be a marker of sickness rather than a cause of it.
Dr Brendon Neuen (Royal North Shore Hospital, not involved): Patients who stop for medical reasons are typically sicker and will do worse; the study cannot separate cause from coincidence.
Natalie Raffoul (The Heart Foundation, not involved): The data is interesting and points a spotlight on potentially significant negative consequences of stopping, but more research is needed.
What to Watch
- Further studies that control for the reasons patients stop GLP-1s, to clarify whether the association is causal or a marker of underlying health.
- Long-term trials examining dose reduction or intermittent use rather than complete cessation, which could help patients who struggle with side effects maintain benefits.
- Regulatory and clinical guidance updates: whether the FDA or European Medicines Agency will strengthen warnings about the risks of discontinuation.
Checked
12 claims in this story checked against 2 sources: 10 supported.
Show each claim
- Partly supportedStopping GLP-1 drugs was linked to roughly double the risk of heart attack, stroke or death compared with continuing them.Euronews: “stopping such medicines was linked to a doubled combined risk of non-fatal heart attack, non-fatal stroke, or death from any cause compared to those who continued.”
- Partly supportedAbout four in 100 people who stopped treatment had an event, compared with about two in 100 who continued.Euronews: “This equates to roughly four events per 100 people per year among those who stopped, compared with two per 100 among those who continued.”
- SupportedThe risk increase was 127% among people with obesity and 61% among those without obesity.Euronews: “People with obesity (a body mass index above 30) had a 127% higher cardiovascular risk after coming off GLP-1s, compared with a 61% increase among those without obesity.”
- SupportedThe study covered more than 80,000 Italian patients.Just In: “The study, published today in The Lancet Regional Health — Europe journal, followed more than 80,000 Italians with type 2 diabetes and no established cardiovascular disease between 2004 and 2024.”
- SupportedAbout 60 per cent of the 80,302 participants stopped their medication.Just In: “About 60 per cent of the 80,302 total participants stopped using their medication.”
- SupportedCeriello said, “[The strength] of the link has been surprising; almost doubling the risk of [cardiovascular disease],”Just In: “[The strength] of the link has been surprising; almost doubling the risk of [cardiovascular disease],” Professor Ceriello said.”
- SupportedChow said the core conclusion “might be misleading” without understanding why participants stopped taking the drugs.Just In: “Clara Chow, academic director of the Westmead Applied Research Centre at the University of Syndey who did not contribute to the study, said the core conclusion “might be misleading” without a deeper understanding of why participants stopped using GLP-1 drugs.”
- SupportedChow said, “If you've discontinued medication, is it because you feel sick taking it? Or you've got another illness? Or you've got a problem that interacts with it … there's a lot of reasons why people stop treatment,”Just In: “"If you've discontinued medication, is it because you feel sick taking it? Or you've got another illness? Or you've got a problem that interacts with it … there's a lot of reasons why people stop treatment."”
- SupportedChow said the group who stopped had a very high rate of death by any cause, suggesting they could have been sicker than those who continued.Just In: “Professor Chow said the group who stopped using the medication also had a very high rate of death by any cause, suggesting they could have been sicker than the group who continued with it.”
- SupportedNeuen said, “They might have stopped for an appropriate [medical] reason, but those patients are typically sicker, and they're going to do worse,”Just In: “"They might have stopped for an appropriate [medical] reason, but those patients are typically sicker, and they're going to do worse," he said.”
- SupportedBecause the study was observational, it cannot determine whether stopping GLP-1s directly caused the increased risk or whether those who stopped were already in poorer health.Euronews: “However, because it was an observational study, it cannot determine whether discontinuing GLP-1s directly causes the increased risk or whether people who stopped were already in poorer health.”
- SupportedRaffoul said the data was “interesting” but more research was needed, and that stopping could have significant negative consequences.Just In: “Natalie Raffoul, head of clinical strategy at The Heart Foundation who did not contribute to the study, said while the data was "interesting", more research was needed.”
