A new international study published in The Lancet Regional Health — Europe suggests people with type 2 diabetes who start and then stop GLP-1 receptor agonist drugs may face a sharply higher risk of serious outcomes.

Researchers followed more than 80,000 Italians with type 2 diabetes and no established cardiovascular disease, treated across 301 diabetes clinics between 2004 and 2024, comparing those who discontinued the medication with those who stayed on it over four years.

About four in 100 people who stopped had a heart attack, stroke or died from any cause, compared with about two in 100 who kept using the drugs.

Lead author Antonio Ceriello, head of diabetes research at the Italian hospital IRCCS MultiMedica, told ABC News the association was "not a complete surprise", but the scale of it was striking: "almost doubling the risk" of cardiovascular disease.

Earlier research had already shown that people who quit GLP-1s commonly regain weight and see blood pressure and blood sugar worsen.

Yet in this study those increases were modest, and appeared both in people who later had an event and in those who did not — leading Ceriello to theorise the drugs may offer direct cardiovascular protection that is lost when treatment ends.

Australian specialists urged caution, with the study unable to prove causation and no data collected on why participants stopped.

About 60 per cent of the 80,302 participants discontinued, and Clara Chow of the University of Sydney's Westmead Applied Research Centre told ABC News the core conclusion "might be misleading" because discontinuation "is a marker of the fact that they're sick as opposed to a cause of their sickness".

According to The Pharmacist, the authors themselves note stopping may "represent a marker of higher underlying risk", and Professor Naveed Sattar of the University of Glasgow said the observational data should be read as associations, not proof that stopping directly causes harm.

The Pharmacist reports that people who stopped the drugs were about twice as likely to suffer a non-fatal heart attack or stroke or die from any cause, and were more than four times as likely to die from any cause than those who continued.

Discontinuation is common in routine practice — studies cited by the authors report 20–50 per cent of patients stop within the first year — with side effects, cost and doubts about effectiveness among the reasons given.

Notably, the study included no tirzepatide users and only a small number taking semaglutide; most participants used liraglutide or dulaglutide.

About half a million Australians use GLP-1 receptor agonists regularly each month, ABC News reports, so questions about stopping affect a very large population.

Separate research adds to the pressure to stay under medical care: The West Australian reports a University of Western Australia study in Nature Medicine found people on tirzepatide who lifted weights three times a week lost 25 per cent less lean tissue than non-trainers, and gained 10 per cent strength while non-exercisers lost 10 per cent — underlining that total health on these drugs involves more than the prescription alone.

Despite the limitations, Royal North Shore Hospital's Associate Professor Brendon Neuen told ABC News the study suggests "long-term treatment is important" for people whose GLP-1 drug is helping a chronic condition, and that anyone considering stopping should talk to a health professional first.

Chow added that people taking the drugs long term must be monitored, because long-term data is still thin. Neuen framed the work as "one small piece of the puzzle": research continues into whether doses or frequency can be reduced, and what stopping versus continuing really means over time.