For millions of Europeans living with type 2 diabetes, GLP-1 receptor agonists have become a cornerstone of treatment. These drugs, which mimic the natural hormone GLP-1 to regulate blood sugar and suppress appetite, have also shown benefits for heart and kidney health. Yet a substantial number of patients stop taking them within the first year, often due to side effects, cost, or concerns about rare adverse events.
New research published in The Lancet Regional Health Europe suggests that stopping these medications may carry serious consequences. The study, which analyzed electronic health records from more than 300 diabetes clinics across Italy, found that patients who discontinued GLP-1 treatment had twice the risk of non-fatal heart attack, non-fatal stroke, or death from any cause compared to those who stayed on the therapy.
This translates to roughly four events per 100 people per year among those who stopped, versus two per 100 among those who continued. The elevated risk was particularly pronounced in individuals with obesity (BMI above 30), who saw a 127% higher cardiovascular risk after stopping, compared to a 61% increase for those without obesity.
Observational limits
The study, which drew on data from the Italian Association of Clinical Diabetologists database, followed over 80,000 people with type 2 diabetes and no prior cardiovascular disease who started a GLP-1 between 2004 and 2024. Most participants were on earlier-generation GLP-1s; semaglutide, one of the most popular newer drugs, accounted for only a small fraction, and tirzepatide was not included as it entered the Italian market after the study period.
Because the study is observational, it cannot prove that stopping GLP-1s directly causes the increased risk. The authors note that people who stop may already be in poorer health, or that discontinuation could be a marker of underlying cardiovascular risk. Interestingly, after stopping, patients' weight, blood sugar, and blood pressure changed only slightly, and there were no significant differences between those who experienced a cardiovascular event and those who did not. This suggests these traditional risk factors may not fully explain the higher risk.
“Our findings suggest that long-term use of GLP-1 receptor agonists may be important for maintaining overall health benefits in people with type 2 diabetes,” the authors wrote. They called for further research to determine whether stopping directly contributes to increased cardiovascular risk or is instead a sign of worsening health.
The study adds to growing evidence about the importance of adherence to GLP-1 therapy. Previous research has shown that weight regain and deterioration of cardiometabolic risk factors often follow discontinuation. The new findings, however, indicate that the cardiovascular risk may be independent of these changes.
For European healthcare systems, where GLP-1 drugs are widely prescribed but also expensive, the results underscore the need for careful patient management and support to maintain treatment. The study also highlights the importance of monitoring patients who do stop, particularly those with obesity.
As the use of GLP-1s continues to expand across Europe, including for weight management, understanding the consequences of stopping is crucial. The findings also come amid broader discussions about the safety of these drugs, such as recent regulatory warnings about rare vision loss. While the benefits are clear, the risks of discontinuation are now better understood.
