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

Chengsheng Ju ; Xi Xiong ORCID logo ; David TW Lui ORCID logo ; Vincent KC Yan ; Matthew Adesuyan ORCID logo ; Ming Xu ; Frederick K Ho ; Carlos KH Wong ORCID logo ; Ian CK Wong ; Esther WY Chan ORCID logo ; +1 more... Li Wei ORCID logo ; (2025) Comparative effect of aspirin versus clopidogrel monotherapy on incident type 2 diabetes in patients with atherosclerotic cardiovascular diseases: A target trial emulation study. Diabetes research and clinical practice, 222. p. 112082. ISSN 0168-8227 DOI: 10.1016/j.diabres.2025.112082
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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 usingthe 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.


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