Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes

Aims: To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D). Materials and Methods: This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models. Results: Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15–1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92–2.97) and heart failure (HR 1.97, 95% CI 1.54–2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding. Conclusions: The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment.