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People with type 2 diabetes mellitus (T2DM) who stopped taking a glucagon-like peptide-1 receptor agonist (GLP-1RA) had around twice the risk of heart attack, stroke or death as those who stayed on treatment, an observational study has concluded.
Publishing their findings in The Lancet Regional Health Europe on 9 November 2026, researchers analysed data from 301 diabetes clinics in Italy, collected between 2004 and 2024, which included 80,302 patients who started on a GLP-1RA and had no history of major cardiovascular events when they started treatment.
By their last visit, more than one-third of patients (39.5%, n=31,687) were still on treatment, while nearly two-thirds (60.5%, n= 48,615) had stopped, which was defined as no GLP-1RA prescription in at least two consecutive visits.
After matching 28,713 patients in each group for factors including age, BMI, HbA1c (blood glucose levels) and diabetes duration, the rate of non-fatal heart attack, non-fatal stroke or death from any cause was 3.94 per 100 years in those who stopped, compared with 1.96 in those who continued, the study results showed.
The study results also revealed that death from any cause, which was looked at as a secondary endpoint, was higher still, with 2.23 per 100 person-years in the discontinuation group compared with 0.48 per 100 person-years in the continuation group.
Such a large association “is unlikely to be explained solely by withdrawal of GLP-1RA therapy” and may be partly influenced by other factors, such as illness prompting people to stop treatment, the study authors noted.
According to the study results, the link appeared to be stronger in patients with a BMI of 30 or above (hazard ratio 2.27) than in those below 30 (hazard ratio 1.61).
The researchers also highlighted that previous studies have found that 20-50% of people stop GLP-1RA treatment within the first year, which was mostly owing to gastrointestinal side effects, cost or inconvenience.
The study authors stressed that the findings cannot show cause and effect, adding that they did not know why people stopped. Discontinuation “may represent a higher underlying risk rather than a direct cause of increased cardiovascular risk”, the study authors said.
They also explained that the findings may not apply to people taking GLP-1RAs for obesity without T2DM, or to tirzepatide, which was not yet available during the study.
In addition, the researchers compared changes in risk factors, such as weight, blood pressure and cholesterol, from the start of treatment to 12 and 24 months, between people who stopped treatment and went on to have an event, and those who stopped and did not.
The study findings only demonstrated small differences, which suggests that the higher risk “may not be fully explained by deterioration of traditional risk factors alone”, the study authors noted.
Commenting on the study, Faye Riley, research communications lead at charity Diabetes UK, said the findings should be “interpreted with caution”.
“This was an observational study, so we can’t tell whether stopping taking GLP-1s directly raised people’s risk of heart attack and stroke, or if those who discontinued treatment were already experiencing health problems,” she added.
“The findings reinforce the importance of supporting people to stay on treatments that work for them. Anyone with T2DM who is considering stopping treatment should speak to their healthcare team first.”
Previous research published in January 2026 has shown that people who used weight-loss medications regained weight more rapidly than those who followed behavioural weight management programmes.
