Koomen JV, Heerspink HJL, Schrieks IC, et al. - In the AleCardio trial, a total of 7,226 patients were recruited and randomized to receive aleglitazar 150 μg or matching placebo on top of standard care in order to assess whether the safety signals could be allocated to raised exposure to aleglitazar. In exposure to aleglitazar, concomitant use of clopidogrel was recognized as a covariate that described interindividual variability. A supplementary reduction of HbA1c, at the expense of an extra decline in haemoglobin, and a rise in serum creatinine and adiponectin was exhibited by individuals who used clopidogrel. Moreover, clopidogrel was found to be a modest inhibitor of CYP2C8. A pharmacokinetic interaction could describe variations in exposure and response to aleglitazar since aleglitazar is metabolized by CYP2C8.