Comparative effect of aspirin versus clopidogrel monotherapy on incident type 2 diabetes in patients with atherosclerotic cardiovascular diseases: A target trial emulation study

Aims: To compare the effects of low-dose aspirin and clopidogrel on the risk of incident type 2 diabetes among patients with ASCVD. Methods: This target trial emulation study was performed using the IQVIA Medical Research Data UK primary care database, including adults with an incident first ASCVD event who initiated low-dose aspirin or clopidogrel between 2004 and 2021. We applied an overlap weighting approach to balance treatment groups. The observational analogues of intention-to-treat and per-protocol effects were estimated using pooled logistic regression. Results: A total of 111,292 ASCVD patients who initiated aspirin (n = 78,012) or clopidogrel (n = 33,280) were included. In intention-to-treat analyses, aspirin and clopidogrel had similar risks of diabetes (Hazard ratio [HR] 1.02, 95 % Confidence interval [CI] 0.96 to 1.07), cardiovascular events (1.00, 0.95 to 1.05), and bleeding events (1.02, 0.97 to 1.08). In per-protocol analyses, risks remained comparable for diabetes (1.06, 0.97 to 1.15), cardiovascular events (0.96, 0.89 to 1.03), and bleeding events (1.01, 0.92 to 1.10). Conclusions: Aspirin and clopidogrel have similar risks of incident diabetes, cardiovascular events, and bleeding events among patients with ASCVD. The choice between these agents may thus be influenced more by factors like cost, patient preference, or tolerance than by clinical outcomes alone.