Quit a GLP-1 drug with type 2 diabetes and the rate of heart attack, stroke or death doubled in an 80,000-patient study. The catch is why

Stopping a GLP-1 drug was linked to roughly double the rate of heart attack, stroke or death in people with type 2 diabetes, in one of the largest real-world looks yet at what happens after the injections end.

The study, published on 9 November in The Lancet Regional Health – Europe, followed 80,302 people with type 2 diabetes treated at 301 diabetes clinics across Italy between 2004 and 2024. All had started a GLP-1 receptor agonist, the drug class that includes Ozempic, and none had a history of major heart events when they began.

By their last clinic visit, 60.5 per cent, or 48,615 people, had stopped, defined as no new prescription at two visits in a row. The researchers matched 28,713 people who stopped with the same number who continued, on age, weight, blood sugar and how long they had had diabetes.

What did they find?

In the group that stopped, non-fatal heart attacks, non-fatal strokes and deaths from any cause together ran at 3.94 per 100 person-years. Among those who kept going, the figure was 1.96. In plain terms: about four events a year for every 100 people who stopped, against about two for every 100 who did not.

Most of the gap came from deaths. Deaths from any cause ran at 2.23 per 100 person-years after stopping, against 0.48 for those still on treatment.

The link was stronger in people with obesity (a BMI of 30 or more), where the risk was more than double, than in those below that mark.

Lead author Antonio Ceriello, head of diabetes research at Italy’s IRCCS MultiMedica, said the link was “not a complete surprise” but its strength was. He suggested the drugs may protect the heart and blood vessels directly, protection that ends when they stop.

Is the drug really the reason?

That is the open question, and the researchers say so themselves. They write that the higher risk is “unlikely to be explained solely by withdrawal” of the drug.

The study did not record why anyone stopped. Earlier research shows 20 to 50 per cent of people quit GLP-1 drugs within the first year, mostly because of stomach side effects, cost or inconvenience. But people also stop because they become seriously ill, and sicker people are more likely to have heart attacks and die.

Clara Chow, academic director of the Westmead Applied Research Centre at the University of Sydney, who was not involved, said the core conclusion “might be misleading”, because stopping may be a marker of illness rather than its cause. Brendon Neuen, an associate professor of medicine at Sydney’s Royal North Shore Hospital, called the study “one small piece of the puzzle”.

There is one clue pointing the other way. Weight, blood pressure and cholesterol rose only modestly after people stopped, which suggests the usual risk factors alone may not explain the gap. The study also left out socio-economic status, a known heart risk, and does not show whether starting and then stopping is worse than never starting at all.

Who does this apply to?

People with type 2 diabetes, in Italy, where the public system pays for these drugs, so cost was unlikely to drive people off them. Most were on liraglutide or dulaglutide. Only a small number used semaglutide, sold as Ozempic and Wegovy, and tirzepatide, sold as Mounjaro, was not yet available during the study.

The findings may not apply to the fast-growing number of people using these drugs purely for weight loss, without diabetes.

What does it mean in Australia?

About half a million Australians regularly use a GLP-1 drug each month, so the question of what happens when people stop is far from academic here.

Natalie Raffoul, head of clinical strategy at the Heart Foundation, called the data interesting and said more research is needed, adding that stopping can carry consequences that may be significant.

The practical advice from every expert is the same: if a GLP-1 drug is helping you manage diabetes, do not stop it on your own. Talk to your doctor first about why you want to stop and what monitoring you need.