The study analyzed electronic medical records from more than 300 clinics in the Italian Association of Clinical Diabetologists database. It covered over 80,000 individuals with type 2 diabetes who had no established cardiovascular disease and started a GLP-1 between 2004 and 2024. The majority of participants received earlier-generation GLP-1s; newer agents like semaglutide accounted for a minor fraction of use, and tirzepatide was excluded as it entered the Italian market after the study period. Patients who continued treatment took the medication for nearly three years on average, whereas those who stopped took it for just over one year.
GLP-1 drugs mimic a natural hormone to regulate blood sugar and curb appetite, serving as a cornerstone of treatment for diabetes and obesity with additional benefits for heart and kidney health. Despite these proven effects, many patients discontinue use within the first year due to gastrointestinal side effects, high costs, or perceived lack of efficacy. Following discontinuation, patients typically experience weight regain and worsening cardiometabolic risk factors, including blood sugar and blood pressure. The study found that the increased risk was more pronounced in people with obesity (BMI above 30), who faced a 127% higher cardiovascular risk after stopping, compared with a 61% increase among those without obesity.
However, the authors caution that this is an observational study and cannot determine causation. It remains unclear whether stopping the drug directly causes the increased risk or if patients who discontinue are already in poorer health. Notably, after treatment cessation, changes in weight, blood sugar, and blood pressure were slight, and there were no significant differences in these markers between those who suffered an event and those who did not. This suggests that standard cardiometabolic factors may not fully explain the observed higher risk.
The findings suggest that long-term use of GLP-1s may be important for maintaining overall health benefits in people with type 2 diabetes and no established cardiovascular disease. The researchers emphasized that further research is needed to determine whether discontinuation directly contributes to increased cardiovascular risk or serves as a marker for worsening underlying health. No specific regulatory action or new policy milestone was announced in conjunction with the publication of these results.
