The relation of regular ibuprofen or paracetamol use with the risk of type 2 diabetes (T2DM) remained undetermined. We aimed to evaluate the prospective association between regular ibuprofen or paracetamol use and incidence of T2DM.

This cohort included 372,843 participants with available data of ibuprofen, paracetamol use and without diabetes at baseline from the UK Biobank. The primary outcome was incident T2DM. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of T2DM.

During a median of 12.1 years’ follow-up, 11,527 (3.1%) participants developed T2DM. Overall, participants with regular use of paracetamol showed a significantly higher risk of incident T2DM (adjusted HR, 1.25; 95%CI: 1.19,1.31), compared with non-users. Moreover, a stronger positive association of paracetamol use with incident T2DM was found among those aged <60 years (vs. ≥60 years, P-interaction =0.008), free of cardiovascular diseases (CVD) (vs. CVD patients, P-interaction =0.01), and without the use of anti-hypertensive drugs (vs. users, P-interaction =0.016) at baseline. However, there was no significant association between regular use of ibuprofen (users vs. non-users; adjusted HR, 1.05; 95%CI: 0.99,1.12) and incident T2DM. More importantly, genetic risks of T2DM did not significantly modify the relations of ibuprofen, or paracetamol use with incident T2DM (Both P-interactions >0.05).

Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of incident T2DM among middle aged UK adults. Our current findings highlight the need for greater consideration in the clinical selection of paracetamol or ibuprofen.